Complicated Urinary Tract Infection (cUTI) Including Acute PyelonephritisPhase 3NCT01595438
Ceftazidime-Avibactam Compared With Doripenem Followed by Oral Therapy for Hospitalized Adults With Complicated UTIs (Urinary Tract Infections)
A Phase 3 study testing Ceftazidime - Avibactam ( CAZ-AVI), Doripenem and Either switch to oral therapy: 500 mg of Ciprofloxacin (oral) in people with Complicated Urinary Tract Infection (cUTI) Including Acute Pyelonephritis, run by Pfizer at 80 sites in 22 countries.
Trial summary
The purpose of this study is to evaluate the effects of Ceftazidime Avibactam compared to Doripenem for treating hospitalized patients with complicated urinary tract infections, including acute pyelonephritis Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Complicated Urinary Tract Infection (cUTI) Including Acute Pyelonephritis
- What is being tested?
- Ceftazidime - Avibactam ( CAZ-AVI), Doripenem and Either switch to oral therapy: 500 mg of Ciprofloxacin (oral)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 598 participants
- Where
- 80 sitesin 22 countries
- Study dates
- Oct 2012to Aug 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 to 90 years of age inclusive
- Female patients can participate if they are surgically sterile or completed menopause or females capable of having children and agree not to attempt pregnancy while receiving IV study therapy and for a period of 7 days after
- Has pyuria with >/= 10 WBCs (white blood cell) and has a positive urine culture within 48 hours of enrollment containing >/=10 to the fifth CFU (colony forming unit ) /ml of a recognized uropathogen known to be susceptible to IV study therapy (CAZ-AVI and doripenem)
- Demonstrates either acute pyelonephritis or complicated lower UTI without pyelonephritis.
Who cannot join
- Urine pathogen is a Gram-positive pathogen or a uropathogen resistant to CAZ-AVI or doripenem
- Patient's urine culture at study entry isolates more than 2 microorganisms regardless of colony count or patient has a confirmed fungal UTI
- Patient is receiving hemodialysis or peritoneal dialysis or had a renal transplant
- Patient is immunocompromised
- Patient is considered unlikely to survive the 6- to 8-week study period or has a rapidly progressive or terminal illness including septic shock which is associated with a high risk of mortality
Trial locations and contacts
80 sites in 22 countries.
80 sites in 22 countries
Japan11 sites
Research Site
Fukuoka
Research Site
Koshigaya-shi
Research Site
Kyoto
Research Site
Nagoya
Research Site
Nara
Research Site
Ōita
Research Site
Sendai
Research Site
Sunto-gun
Research Site
Tokushima
Research Site
Ueda-shi
Research Site
Utsunomiya
Russia9 sites
Research Site
Arkhangelsk
Research Site
Krasnodar
Research Site
Moscow
Research Site
Novosibirsk
Research Site
Penza
Research Site
Rostov-on-Don
Research Site
Saint Petersburg
Research Site
Saratov
Research Site
Vsevolozhsk
Ukraine9 sites
Research Site
Cherkasy
Research Site
Dnipropetrovsk
Research Site
Kharkiv
Research Site
Kyiv
Research Site
Lviv
Research Site
Mykolaiv
Research Site
Odesa
Research Site
Uzhhorod
Research Site
Zaporizhzhya
Brazil6 sites
Research Site
Belo Horizonte
Research Site
Campinas/SP
Research Site
Salvador
Research Site
São José Do Rio Preto - SP
Research Site
São Paulo
Research Site
Vila Clementino
Romania5 sites
Research Site
Brasov
Research Site
Bucharest
Research Site
Cluj-Napoca
Research Site
Craiova
Research Site
Iași
Argentina4 sites
Research Site
Córdoba
Research Site
Corrientes
Research Site
Mendoza
Research Site
Santa Fe
Hungary4 sites
Research Site
Budapest
Research Site
Nagykanizsa
Research Site
Nyíregyháza
Research Site
Zalaegerszeg
Slovakia4 sites
Research Site
Poprad
Research Site
Prešov
Research Site
Trnava
Research Site
Žilina
United States3 sites
Research Site
Lima, Ohio
Research Site
Royal Oak, Michigan
Research Site
Sylmar, California
Israel3 sites
Research Site
Jerusalem
Research Site
Petah Tikva
Research Site
Safed
South Korea3 sites
Research Site
Busan
Research Site
Seoul
Research Site
Wŏnju
About this study
Official title: A Phase III, Randomized, Multicenter, Double-Blind, Double Dummy, Parallel Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam (CAZ-AVI, Formerly CAZ104) Versus Doripenem Followed by Appropriate Oral Therapy in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, With a Gram Negative Pathogen in Hospitalized Adults
The purpose of this study is to evaluate the effects of Ceftazidime Avibactam compared to Doripenem for treating hospitalized patients with complicated urinary tract infections, including acute pyelonephritis
Read the detailed description
A Phase III, Randomized, Multicenter, Double-Blind, Double Dummy, Parallel Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam (CAZ-AVI, formerly CAZ104) Versus Doripenem Followed by Appropriate Oral Therapy in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, With a Gram Negative Pathogen in Hospitalized Adults
- Being tested
- Ceftazidime - Avibactam ( CAZ-AVI), Doripenem, Either switch to oral therapy: 500 mg of Ciprofloxacin (oral), or switch to oral therapy: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral)
- Keywords
- Ceftazidime, Avibactam, Doripenem, Ciprofloxacin, sulfamethoxazole/trimethoprim, Anti-Infective Agents, Complicated Urinary Tract Infection,Acute Pyelonephritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ceftazidime - Avibactam ( CAZ-AVI)Drug
Ceftazidime 2000 mg and 500 mg of avibactam. Patients randomized to receive CAZ-AVI will receive an infusion of CAZ-AVI (2000 mg ceftazidime and 500 mg avibactam) every 8 hours administered by intravenous (IV) infusion in a volume of 100 mL at a constant rate over 120 minutes
DoripenemDrug
500 mg of Doripenem. Patients randomized to receive Doripenem will receive an infusion of Doripenem 500 mg every 8 hours administered by intravenous (IV) infusion in a volume of 100 mL at a constant rate over 60 minutes
Either switch to oral therapy: 500 mg of Ciprofloxacin (oral)Drug
Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement
or switch to oral therapy: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral)Drug
Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement
| Study group | Role | What they receive |
|---|---|---|
| Ceftazidime - Avibactam ( CAZ-AVI) | Experimental | IV treatment Receives: Drug: Ceftazidime - Avibactam ( CAZ-AVI); Drug: Either switch to oral therapy: 500 mg of Ciprofloxacin (oral); Drug: or switch to oral therapy: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral) |
| Doripenem | Active comparator | IV treatment Receives: Drug: Doripenem; Drug: Either switch to oral therapy: 500 mg of Ciprofloxacin (oral); Drug: or switch to oral therapy: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patient-reported Symptomatic Response at Day 5 (mMITT Analysis Set): Non-inferiority Hypothesis Test
Number of patients with symptomatic resolution (or return to premorbid state) of UTI-specific symptoms except flank pain (frequency/urgency/dysuria/suprapubic pain) with resolution of or improvement in flank pain based on the patient-reported symptom assessment response at the Day 5 visit in the mMITT analysis set. The sponsor will conclude noninferiority if the lower limit of the 95% CI of difference (corresponding to a 97.5% 1-sided lower bound) is greater than -12.5% for both FDA coprimary outcome variables (symptomatic resolution at day 5 or favorable combined response at test of cure (TOC)).
Measured: At Day 5 visit. Day 5 visit is based on 24 hour periods from the first dose date and time.
Combined Patient-reported Symptomatic and Microbiological Response at TOC (mMITT Analysis Set): Non-inferiority Hypothesis Test
Number of patients with both a favorable per patient microbiological response and symptomatic resolution (or return to premorbid state) of all UTI-specific symptoms (frequency/urgency/dysuria/suprapubic pain/flank pain) based on the patient-reported symptom assessment response at the TOC visit in the mMITT analysis set. The sponsor will conclude noninferiority if the lower limit of the 95% CI of difference (corresponding to a 97.5% 1-sided lower bound) is greater than -12.5% for both FDA coprimary outcome variables (symptomatic resolution at day 5 or favorable combined response at test of cure (TOC)).
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Per-patient Microbiological Response at TOC (mMITT Analysis Set): Non-inferiority Hypothesis Test
Number of patients with a favorable per patient microbiological response at TOC. The primary efficacy outcome variable for ROW is the proportion of patients with a favorable per-patient microbiological response at the TOC visit in the mMITT analysis set.
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Secondary outcomes (60)
Per-patient Microbiological Response at EOT (IV) (mMITT Analysis Set)
Number of patients with a favorable per-patient microbiological response at EOT (IV)
Measured: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Per-patient Microbiological Response at LFU (mMITT Analysis Set)
Number of patients with a favorable per patient microbiological response at LFU
Measured: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Per-patient Microbiological Response at EOT (IV) (ME at EOT (IV) Analysis Set)
Number of patients with a favorable per-patient microbiological response at EOT (IV)
Measured: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Per-patient Microbiological Response at TOC (ME at TOC Analysis Set)
Number of patients with a favorable per patient microbiological response at TOC
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Per-patient Microbiological Response at LFU (ME at LFU Analysis Set)
Number of patients with a favorable per patient microbiological response at LFU
Measured: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Per-patient Microbiological Response at EOT (IV) (Extended ME at EOT (IV) Analysis Set)
Number of patients with a favorable per-patient microbiological response at EOT (IV)
Measured: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Per-patient Microbiological Response at TOC (Extended ME at TOC Analysis Set)
Number of patients with a favorable per patient microbiological response at TOC
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Per-patient Microbiological Response at LFU (Extended ME at LFU Analysis Set)
Number of patients with a favorable per patient microbiological response at LFU
Measured: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Investigator Determined Clinical Response at EOT (IV) (mMITT Analysis Set)
Number of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Measured: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Investigator Determined Clinical Response at TOC (mMITT Analysis Set)
Number of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Investigator Determined Clinical Response at LFU (mMITT Analysis Set)
Number of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Measured: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Investigator Determined Clinical Response at EOT (IV) (ME at EOT (IV) Analysis Set)
Number of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Measured: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Investigator Determined Clinical Response at TOC (ME at TOC Analysis Set)
Number of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Investigator Determined Clinical Response at LFU (ME at LFU Analysis Set)
Number of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Measured: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Investigator Determined Clinical Response at EOT (IV) (Extended ME at EOT (IV) Analysis Set)
Number of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Measured: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Investigator Determined Clinical Response at TOC (Extended ME at TOC Analysis Set)
Number of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Investigator Determined Clinical Response at LFU (Extended ME at LFU Analysis Set)
Number of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Measured: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Investigator Determined Clinical Response at EOT (IV) (CE at EOT (IV) Analysis Set)
Number of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Measured: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Investigator Determined Clinical Response at TOC (CE at TOC Analysis Set)
Number of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Investigator Determined Clinical Response at LFU (CE at LFU Analysis Set)
Number of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Measured: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (mMITT Analysis Set)
Clinical cure at the TOC visit for patients infected with a ceftazidime resistant pathogen in the mMITT analysis set. Includes patients infected by at least one ceftazidime-resistant Gram-negative pathogen.
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (ME at TOC Analysis Set)
Clinical cure at the TOC visit for patients infected with a ceftazidime resistant pathogen in the ME at TOC analysis set. Includes patients infected by at least one ceftazidime-resistant Gram-negative pathogen.
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (Extended ME at TOC Analysis Set)
Clinical cure at the TOC visit for patients infected with a ceftazidime resistant pathogen in the Extended ME at TOC analysis set. Includes patients infected by at least one ceftazidime-resistant Gram-negative pathogen.
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (mMITT Analysis Set)
Favorable per-patient microbiological response at the TOC visit for patients infected with a ceftazidime resistant pathogen in the mMITT analysis set.
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (ME at TOC Analysis Set)
Favorable per-patient microbiological response at the TOC visit for patients infected with a ceftazidime resistant pathogen in the ME at TOC analysis set.
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (Extended ME at TOC Analysis Set)
Favorable per-patient microbiological response at the TOC visit for patients infected with a ceftazidime resistant pathogen in the Extended ME at TOC analysis set.
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Time to First Defervescence While on IV Study Therapy (mMITT Analysis Set)
Time to first defervescence while on IV study therapy in patients in the mMITT analysis set who have fever at study entry.
Measured: Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.
Time to First Defervescence While on IV Study Therapy (ME at TOC Analysis Set)
Time to first defervescence while on IV study therapy in patients in the ME at TOC analysis set who have fever at study entry.
Measured: Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.
Time to First Defervescence While on IV Study Therapy (Extended ME at TOC Analysis Set)
Time to first defervescence while on IV study therapy in patients in the Extended ME at TOC analysis set who have fever at study entry.
Measured: Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.
Time to First Defervescence While on IV Study Therapy (CE at TOC Analysis Set)
Time to first defervescence while on IV study therapy in patients in the CE at TOC analysis set who have fever at study entry.
Measured: Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.
Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (mMITT Analysis Set)
Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the mMITT analysis set
Measured: At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Per-pathogen Microbiological Response at TOC for Baseline Pathogen (mMITT Analysis Set)
Number of favorable per-pathogen microbiological responses at the TOC visit in the mMITT analysis set
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization
Per-pathogen Microbiological Response at LFU for Baseline Pathogen (mMITT Analysis Set)
Number of favorable per-pathogen microbiological responses at the LFU visit in the mMITT analysis set
Measured: At LFU visit. LFU visit is 45 to 52 days from Randomization
Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (Extended ME at EOT (IV) Analysis Set)
Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the Extended ME at EOT (IV) analysis set
Measured: At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Per-pathogen Microbiological Response at TOC for Baseline Pathogen (Extended ME at TOC Analysis Set)
Number of favorable per-pathogen microbiological responses at the TOC visit in the Extended ME at TOC analysis set
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Per-pathogen Microbiological Response at LFU for Baseline Pathogen (Extended ME at LFU Analysis Set)
Number of favorable per-pathogen microbiological responses at the LFU visit in the Extended ME at LFU analysis set
Measured: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (ME at EOT (IV) Analysis Set)
Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the ME at EOT (IV) analysis set
Measured: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Per-pathogen Microbiological Response at TOC for Baseline Pathogen (ME at TOC Analysis Set)
Number of favorable per-pathogen microbiological responses at the TOC visit in the ME at TOC analysis set
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Per-pathogen Microbiological Response at LFU for Baseline Pathogen (ME at LFU Analysis Set)
Number of favorable per-pathogen microbiological responses at the LFU visit in the ME at LFU analysis set
Measured: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Per-pathogen Microbiological Response at EOT (IV) for Blood Only (mMITT Analysis Set)
Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the mMITT analysis set for blood only
Measured: At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Per-pathogen Microbiological Response at TOC for Blood Only (mMITT Analysis Set)
Number of favorable per-pathogen microbiological responses at the TOC visit in the mMITT analysis set for blood only
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization
Per-pathogen Microbiological Response at LFU for Blood Only (mMITT Analysis Set)
Number of favorable per-pathogen microbiological responses at the LFU visit in the mMITT analysis set for blood only
Measured: At LFU visit. LFU visit is 45 to 52 days from Randomization
Per-pathogen Microbiological Response at EOT (IV) for Blood Only (Extended ME at EOT (IV) Analysis Set)
Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the Extended ME at EOT (IV) analysis set for blood only
Measured: At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Per-pathogen Microbiological Response at TOC for Blood Only (Extended ME at TOC Analysis Set)
Number of favorable per-pathogen microbiological responses at the TOC visit in the Extended ME at TOC analysis set for blood only
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Per-pathogen Microbiological Response at LFU for Blood Only (Extended ME at LFU Analysis Set)
Number of favorable per-pathogen microbiological responses at the LFU visit in the Extended ME at LFU analysis set for blood only
Measured: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Per-pathogen Microbiological Response at EOT (IV) for Blood Only (ME at EOT (IV) Analysis Set)
Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the ME at EOT (IV) analysis set for blood only
Measured: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Per-pathogen Microbiological Response at TOC for Blood Only (ME at TOC Analysis Set)
Number of favorable per-pathogen microbiological responses at the TOC visit in the ME at TOC analysis set for blood only
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Per-pathogen Microbiological Response at LFU for Blood Only (ME at LFU Analysis Set)
Number of favorable per-pathogen microbiological responses at the LFU visit in the ME at LFU analysis set for blood only
Measured: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Per-pathogen Microbiological Response at TOC by CAZ AVI MIC for Baseline Pathogen (mMITT Analysis Set)
Per pathogen microbiological response at TOC by CAZ-AVI MIC for baseline pathogen in the mMITT analysis set
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization
Per-pathogen Microbiological Response at TOC by CAZ AVI MIC for Baseline Pathogen (Extended ME at TOC Analysis Set)
Per pathogen microbiological response at TOC by CAZ-AVI MIC for baseline pathogen in the Extended ME at TOC analysis set
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization
Per-pathogen Microbiological Response at TOC by CAZ AVI MIC for Baseline Pathogen (ME at TOC Analysis Set)
Per pathogen microbiological response at TOC by CAZ-AVI MIC for baseline pathogen in the ME at TOC analysis set
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization
Per-pathogen Microbiological Response at TOC by Doripenem MIC for Baseline Pathogen (mMITT Analysis Set)
Per pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen in the mMITT analysis set
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization
Per-pathogen Microbiological Response at TOC by Doripenem MIC for Baseline Pathogen (Extended ME at TOC Analysis Set)
Per pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen in the Extended ME at TOC analysis set
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization
Per-pathogen Microbiological Response at TOC by Doripenem MIC for Baseline Pathogen (ME at TOC Analysis Set)
Per pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen in the ME at TOC analysis set
Measured: At TOC visit. TOC visit is 21 to 25 days from Randomization
Plasma Concentrations for Ceftazidime Within 15 Minutes Before/After Dose (PK Analysis Set)
Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.
Measured: within 15 minutes before/after dose
Plasma Concentrations for Ceftazidime Between 30 to 90 Minutes After Dose(PK Analysis Set)
Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.
Measured: Between 30 to 90 minutes after dose
Plasma Concentrations for Ceftazidime Between 300 to 360 Minutes After Dose(PK Analysis Set)
Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.
Measured: Between 300 to 360 minutes after dose
Plasma Concentrations for Avibactam Within 15 Minutes Before/After Dose (PK Analysis Set)
Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.
Measured: within 15 minutes before/after dose
Plasma Concentrations for Avibactam Between 30 to 90 Minutes After Dose(PK Analysis Set)
Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.
Measured: Between 30 to 90 minutes after dose
Plasma Concentrations for Avibactam Between 300 to 360 Minutes After Dose(PK Analysis Set)
Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.
Measured: Between 300 to 360 minutes after dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2012 (estimated)
- Study startOct 2012
- Primary completionAug 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Complicated Urinary Tract Infection (cUTI) Including Acute PyelonephritisStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 598 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Forest Laboratories
- Responsible party
- Sponsor
- Investigators
- Paul Newell, MBBS, MRCP, Study director, AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01595438
- Sponsor's protocol ID
- D4280C00002
- Other IDs
- 2011-005721-43
- Status last verified
- Aug 2017
- First submitted
- 27 Apr 2012
- Last updated
- 6 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Cheng K, Newell P, Chow JW, Broadhurst H, Wilson D, Yates K, Wardman A. Safety Profile of Ceftazidime-Avibactam: Pooled Data from the Adult Phase II and Phase III Clinical Trial Programme. Drug Saf. 2020 Aug;43(8):751-766. doi: 10.1007/s40264-020-00934-3.
PubMed 32602065Li J, Lovern M, Green ML, Chiu J, Zhou D, Comisar C, Xiong Y, Hing J, MacPherson M, Wright JG, Riccobene T, Carrothers TJ, Das S. Ceftazidime-Avibactam Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Across Adult Indications and Patient Subgroups. Clin Transl Sci. 2019 Mar;12(2):151-163. doi: 10.1111/cts.12585. Epub 2018 Sep 28.
PubMed 30221827Nichols WW, Stone GG, Newell P, Broadhurst H, Wardman A, MacPherson M, Yates K, Riccobene T, Critchley IA, Das S. Ceftazidime-Avibactam Susceptibility Breakpoints against Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2018 Oct 24;62(11):e02590-17. doi: 10.1128/AAC.02590-17. Print 2018 Nov.
PubMed 30061279Stone GG, Newell P, Gasink LB, Broadhurst H, Wardman A, Yates K, Chen Z, Song J, Chow JW. Clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa: pooled data from the ceftazidime/avibactam Phase III clinical trial programme. J Antimicrob Chemother. 2018 Sep 1;73(9):2519-2523. doi: 10.1093/jac/dky204.
PubMed 29912399Wagenlehner FM, Sobel JD, Newell P, Armstrong J, Huang X, Stone GG, Yates K, Gasink LB. Ceftazidime-avibactam Versus Doripenem for the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a Phase 3 Randomized Trial Program. Clin Infect Dis. 2016 Sep 15;63(6):754-762. doi: 10.1093/cid/ciw378. Epub 2016 Jun 16.
PubMed 27313268
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized, Multicenter, Double-Blind, Double Dummy, Parallel Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam (CAZ-AVI, Formerly CAZ104) Versus Doripenem Followed by Appropriate Oral Therapy in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, With a Gram Negative Pathogen in Hospitalized Adults
- ClinicalTrials.gov ID
- NCT01595438
- Acronym / sponsor ID
- D4280C00002
- Keywords
- Ceftazidime, Avibactam, Doripenem, Ciprofloxacin, sulfamethoxazole/trimethoprim, Anti-Infective Agents, Complicated Urinary Tract Infection,Acute Pyelonephritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 598 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Collaborators
- Forest Laboratories
- Study start
- Oct 2012
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 10 May 2012 (estimated)
- Results
- Posted 9 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the effects of Ceftazidime Avibactam compared to Doripenem for treating hospitalized patients with complicated urinary tract infections, including acute pyelonephritis
Detailed description
A Phase III, Randomized, Multicenter, Double-Blind, Double Dummy, Parallel Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam (CAZ-AVI, formerly CAZ104) Versus Doripenem Followed by Appropriate Oral Therapy in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, With a Gram Negative Pathogen in Hospitalized Adults
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ceftazidime - Avibactam ( CAZ-AVI) | Experimental | Drug: Ceftazidime - Avibactam ( CAZ-AVI), Drug: Either switch to oral therapy: 500 mg of Ciprofloxacin (oral), Drug: or switch to oral therapy: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral)IV treatment |
| Doripenem | Active comparator | Drug: Doripenem, Drug: Either switch to oral therapy: 500 mg of Ciprofloxacin (oral), Drug: or switch to oral therapy: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral)IV treatment |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 18 to 90 years of age inclusive
- Female patients can participate if they are surgically sterile or completed menopause or females capable of having children and agree not to attempt pregnancy while receiving IV study therapy and for a period of 7 days after
- Has pyuria with >/= 10 WBCs (white blood cell) and has a positive urine culture within 48 hours of enrollment containing >/=10 to the fifth CFU (colony forming unit ) /ml of a recognized uropathogen known to be susceptible to IV study therapy (CAZ-AVI and doripenem)
- Demonstrates either acute pyelonephritis or complicated lower UTI without pyelonephritis.
Key exclusion criteria (5 listed)
- Urine pathogen is a Gram-positive pathogen or a uropathogen resistant to CAZ-AVI or doripenem
- Patient's urine culture at study entry isolates more than 2 microorganisms regardless of colony count or patient has a confirmed fungal UTI
- Patient is receiving hemodialysis or peritoneal dialysis or had a renal transplant
- Patient is immunocompromised
- Patient is considered unlikely to survive the 6- to 8-week study period or has a rapidly progressive or terminal illness including septic shock which is associated with a high risk of mortality
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ceftazidime - Avibactam ( CAZ-AVI)Ceftazidime 2000 mg and 500 mg of avibactam. Patients randomized to receive CAZ-AVI will receive an infusion of CAZ-AVI (2000 mg ceftazidime and 500 mg avibactam) every 8 hours administered by intravenous (IV) infusion in a volume of 100 mL at a constant rate over 120 minutes | Drug | Ceftazidime - Avibactam ( CAZ-AVI) |
| Doripenem500 mg of Doripenem. Patients randomized to receive Doripenem will receive an infusion of Doripenem 500 mg every 8 hours administered by intravenous (IV) infusion in a volume of 100 mL at a constant rate over 60 minutes | Drug | Doripenem |
| Either switch to oral therapy: 500 mg of Ciprofloxacin (oral)Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement | Drug | Ceftazidime - Avibactam ( CAZ-AVI), Doripenem |
| or switch to oral therapy: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral)Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement | Drug | Ceftazidime - Avibactam ( CAZ-AVI), Doripenem |
Primary outcome
Patient-reported Symptomatic Response at Day 5 (mMITT Analysis Set): Non-inferiority Hypothesis Test
Time frame: At Day 5 visit. Day 5 visit is based on 24 hour periods from the first dose date and time.
Number of patients with symptomatic resolution (or return to premorbid state) of UTI-specific symptoms except flank pain (frequency/urgency/dysuria/suprapubic pain) with resolution of or improvement in flank pain based on the patient-reported symptom assessment response at the Day 5 visit in the mMITT analysis set. The sponsor will conclude noninferiority if the lower limit of the 95% CI of difference (corresponding to a 97.5% 1-sided lower bound) is greater than -12.5% for both FDA coprimary outcome variables (symptomatic resolution at day 5 or favorable combined response at test of cure (TOC)).
Combined Patient-reported Symptomatic and Microbiological Response at TOC (mMITT Analysis Set): Non-inferiority Hypothesis Test
Time frame: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Number of patients with both a favorable per patient microbiological response and symptomatic resolution (or return to premorbid state) of all UTI-specific symptoms (frequency/urgency/dysuria/suprapubic pain/flank pain) based on the patient-reported symptom assessment response at the TOC visit in the mMITT analysis set. The sponsor will conclude noninferiority if the lower limit of the 95% CI of difference (corresponding to a 97.5% 1-sided lower bound) is greater than -12.5% for both FDA coprimary outcome variables (symptomatic resolution at day 5 or favorable combined response at test of cure (TOC)).
Per-patient Microbiological Response at TOC (mMITT Analysis Set): Non-inferiority Hypothesis Test
Time frame: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Number of patients with a favorable per patient microbiological response at TOC. The primary efficacy outcome variable for ROW is the proportion of patients with a favorable per-patient microbiological response at the TOC visit in the mMITT analysis set.
60 secondary outcomes
Per-patient Microbiological Response at EOT (IV) (mMITT Analysis Set)
Time frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Per-patient Microbiological Response at LFU (mMITT Analysis Set)
Time frame: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Per-patient Microbiological Response at EOT (IV) (ME at EOT (IV) Analysis Set)
Time frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Per-patient Microbiological Response at TOC (ME at TOC Analysis Set)
Time frame: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Per-patient Microbiological Response at LFU (ME at LFU Analysis Set)
Time frame: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Per-patient Microbiological Response at EOT (IV) (Extended ME at EOT (IV) Analysis Set)
Time frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Per-patient Microbiological Response at TOC (Extended ME at TOC Analysis Set)
Time frame: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Per-patient Microbiological Response at LFU (Extended ME at LFU Analysis Set)
Time frame: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Investigator Determined Clinical Response at EOT (IV) (mMITT Analysis Set)
Time frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Investigator Determined Clinical Response at TOC (mMITT Analysis Set)
Time frame: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Investigator Determined Clinical Response at LFU (mMITT Analysis Set)
Time frame: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Investigator Determined Clinical Response at EOT (IV) (ME at EOT (IV) Analysis Set)
Time frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Investigator Determined Clinical Response at TOC (ME at TOC Analysis Set)
Time frame: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Investigator Determined Clinical Response at LFU (ME at LFU Analysis Set)
Time frame: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Investigator Determined Clinical Response at EOT (IV) (Extended ME at EOT (IV) Analysis Set)
Time frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Investigator Determined Clinical Response at TOC (Extended ME at TOC Analysis Set)
Time frame: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Investigator Determined Clinical Response at LFU (Extended ME at LFU Analysis Set)
Time frame: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Investigator Determined Clinical Response at EOT (IV) (CE at EOT (IV) Analysis Set)
Time frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Investigator Determined Clinical Response at TOC (CE at TOC Analysis Set)
Time frame: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Investigator Determined Clinical Response at LFU (CE at LFU Analysis Set)
Time frame: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (mMITT Analysis Set)
Time frame: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (ME at TOC Analysis Set)
Time frame: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (Extended ME at TOC Analysis Set)
Time frame: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (mMITT Analysis Set)
Time frame: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (ME at TOC Analysis Set)
Time frame: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (Extended ME at TOC Analysis Set)
Time frame: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Time to First Defervescence While on IV Study Therapy (mMITT Analysis Set)
Time frame: Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.
Time to First Defervescence While on IV Study Therapy (ME at TOC Analysis Set)
Time frame: Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.
Time to First Defervescence While on IV Study Therapy (Extended ME at TOC Analysis Set)
Time frame: Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.
Time to First Defervescence While on IV Study Therapy (CE at TOC Analysis Set)
Time frame: Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.
Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (mMITT Analysis Set)
Time frame: At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Per-pathogen Microbiological Response at TOC for Baseline Pathogen (mMITT Analysis Set)
Time frame: At TOC visit. TOC visit is 21 to 25 days from Randomization
Per-pathogen Microbiological Response at LFU for Baseline Pathogen (mMITT Analysis Set)
Time frame: At LFU visit. LFU visit is 45 to 52 days from Randomization
Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (Extended ME at EOT (IV) Analysis Set)
Time frame: At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Per-pathogen Microbiological Response at TOC for Baseline Pathogen (Extended ME at TOC Analysis Set)
Time frame: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Per-pathogen Microbiological Response at LFU for Baseline Pathogen (Extended ME at LFU Analysis Set)
Time frame: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (ME at EOT (IV) Analysis Set)
Time frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Per-pathogen Microbiological Response at TOC for Baseline Pathogen (ME at TOC Analysis Set)
Time frame: At TOC visit. TOC visit is 21 to 25 days from Randomization.
Per-pathogen Microbiological Response at LFU for Baseline Pathogen (ME at LFU Analysis Set)
Time frame: At LFU visit. LFU visit is 45 to 52 days from Randomization.
Per-pathogen Microbiological Response at EOT (IV) for Blood Only (mMITT Analysis Set)
Time frame: At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32602065Cheng K, Newell P, Chow JW, Broadhurst H, Wilson D, Yates K, Wardman A. Safety Profile of Ceftazidime-Avibactam: Pooled Data from the Adult Phase II and Phase III Clinical Trial Programme. Drug Saf. 2020 Aug;43(8):751-766. doi: 10.1007/s40264-020-00934-3.
- Derived from this study: PubMed 30221827Li J, Lovern M, Green ML, Chiu J, Zhou D, Comisar C, Xiong Y, Hing J, MacPherson M, Wright JG, Riccobene T, Carrothers TJ, Das S. Ceftazidime-Avibactam Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Across Adult Indications and Patient Subgroups. Clin Transl Sci. 2019 Mar;12(2):151-163. doi: 10.1111/cts.12585. Epub 2018 Sep 28.
- Derived from this study: PubMed 30061279Nichols WW, Stone GG, Newell P, Broadhurst H, Wardman A, MacPherson M, Yates K, Riccobene T, Critchley IA, Das S. Ceftazidime-Avibactam Susceptibility Breakpoints against Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2018 Oct 24;62(11):e02590-17. doi: 10.1128/AAC.02590-17. Print 2018 Nov.
- Derived from this study: PubMed 29912399Stone GG, Newell P, Gasink LB, Broadhurst H, Wardman A, Yates K, Chen Z, Song J, Chow JW. Clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa: pooled data from the ceftazidime/avibactam Phase III clinical trial programme. J Antimicrob Chemother. 2018 Sep 1;73(9):2519-2523. doi: 10.1093/jac/dky204.
- Derived from this study: PubMed 27313268Wagenlehner FM, Sobel JD, Newell P, Armstrong J, Huang X, Stone GG, Yates K, Gasink LB. Ceftazidime-avibactam Versus Doripenem for the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a Phase 3 Randomized Trial Program. Clin Infect Dis. 2016 Sep 15;63(6):754-762. doi: 10.1093/cid/ciw378. Epub 2016 Jun 16.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Newell, MBBS, MRCP study director
AstraZeneca
80 sites in 22 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ceftazidime - Avibactam ( CAZ-AVI), Doripenem and Either switch to oral therapy: 500 mg of Ciprofloxacin (oral) in people with Complicated Urinary Tract Infection (cUTI) Including Acute Pyelonephritis, run by Pfizer at 80 sites in 22 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 80 sites in Japan, Russia, Ukraine, Brazil, Romania and 17 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient-reported Symptomatic Response at Day 5 (mMITT Analysis Set): Non-inferiority Hypothesis Test (time frame: At Day 5 visit. Day 5 visit is based on 24 hour periods from the first dose date and time.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01595438, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2017.