Gram-negative Bacterial InfectionsPhase 2NCT05639647
Study of 2 Medicines (Aztreonam and Avibactam) Compared to Best Available Therapy for Serious Gram-negative Infections
A Phase 2 study testing ATM-AVI and BAT in people with Gram-negative Bacterial Infections, run by Pfizer at 23 sites in 8 countries.
Trial summary
The purpose of this study is to evaluate how Aztreonam (ATM) and Avibactam (AVI) are processed in pediatric participants. This study also aims to understand participant safety and effects in pediatric participants. Read more about this study
- Who is it for?
- Ages 9 months to 17 years
- Conditions the study is for
- Gram-negative Bacterial Infections
- What is being tested?
- ATM-AVI and BAT
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 23 sitesin 8 countries
- Study dates
- 18 Apr 2023to 31 Mar 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 9 months to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Participants must meet the following key inclusion criteria to be eligible for enrollment into the study:
- Participants ≥9 months to <18 years of age at Screening; Female (post-menarchal) participants must have a negative serum/urine pregnancy test (β hCG sensitivity ≥25 mIU/mL).
- Suspected/confirmed cIAI, cUTI, HAP/VAP, or BSI with gram-negative pathogens.
- Require hospitalization and IV antibiotic treatment.
Who cannot join
- Participants with any of the following characteristics/conditions will be excluded:
- Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
- Gram-negative species not expected to respond to ATM AVI ≤14 days.
- Pregnant or breastfeeding; fertile male/female unwilling/unable to use effective contraception for at ≥7 days (males) or ≥28 days (females) after last ATM-AVI infusion.
- (HAP/VAP only):
- Microbiologically known or high likelihood of monomicrobial infection with a gram-positive organism, lung abscess, pleural empyema, or post-obstructive pneumonia, lung or heart transplant.
Show all 11Show fewer
- Received >24 hours of systemic antibiotics during the 48 hours before randomization unless participant has documented treatment failure after at least 48 hours of antibiotic therapy.
- Current use of any prohibited concomitant medication(s) or unwilling/unable (Cockayne Syndrome patients with cIAI are excluded) to use MTZ or having received previous investigational drug(s) or vaccine ≤30 days or 5 half-lives before randomization (whichever is longer).
- CrCL ≤15 mL/min/1.73 m2 (eCrCl or eGFR calculation based on age).
- Non-infectious related screening ALT or AST >3 x ULN, ALP >3 x ULN and/or TBili >2 x ULN (> 3 x ULN for Gilbert's syndrome).
- Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
Trial locations and contacts
23 sites in 8 countries. Contact the study team or a site near you to ask about taking part.
23 sites in 8 countries
Spain5 sites, 5 recruiting
- Recruiting
Hospital Germans Trias i Pujol
Badalona, Barcelona [barcelona], 08916
- Recruiting
Hospital Universitari Vall d'Hebron
Barcelona, 08035
- Recruiting
Hospital Sant Joan de Déu
Esplugues de Llobregat, Barcelona [barcelona], 08950
- Recruiting
Hospital Universitario La Paz
Madrid, Madrid, Comunidad de, 28046
- Recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
United States3 sites, 3 recruiting
- Recruiting
Weill Cornell Medicine-New York Presbyterian Hospital
New York, New York, 10021
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
- Recruiting
Rady Children's Hospital
San Diego, California, 92123
China3 sites, 3 recruiting
- Recruiting
Beijing Children's Hospital, Capital Medical University
Beijing, Beijing Municipality, 100045
- Recruiting
Guangzhou Women and Children's Medical Center
Guangzhou, Guangdong, 510623
- Recruiting
Shanghai Children's Medical Center
Shanghai, 200127
India3 sites, 3 recruiting
- Recruiting
RajaRajeswari Medical College and Hospital
Bangalore, Karnataka, 560074
- Recruiting
Institute of Child Health
Kolkata, West Bengal, 700017
- Recruiting
Medanta Hospital Lucknow
Lucknow, Uttar Pradesh, 226030
Taiwan3 sites, 3 recruiting
- Recruiting
Hsinchu Municipal Mackay Children's Hospital
Hsinchu, Hsinchu, 300046
- Recruiting
National Taiwan University Hospital
Taipei, 100225
- Recruiting
Chang Gung Medical Foundation-Linkou Branch
Taoyuan, 333
Greece2 sites, 2 recruiting
- Recruiting
University General Hospital of Heraklion
Heraklion, Irakleío, 715 00
- Recruiting
Ippokrateio General Hospital of Thessaloniki
Thessaloniki, Kentrikí Makedonía, 546 42
Hungary2 sites, 2 recruiting
- Recruiting
Semmelweis Egyetem
Budapest, 1083
- Recruiting
Semmelweis Egyetem
Budapest, 1094
Turkey (Türkiye)2 sites
- Active, not recruiting
Istanbul Universitesi Istanbul Tıp Fakultesi Hastanesi
Istanbul, İ̇stanbul, 34093
- Active, not recruiting
Cukurova Universty
Sarçam, Adana, 01250
About this study
Official title: A PHASE 2A MULTICENTER, OBSERVER-BLINDED, RANDOMIZED 2 ARM STUDY TO INVESTIGATE PHARMACOKINETICS, SAFETY, TOLERABILITY AND EFFICACY OF INTRAVENOUS AZTREONAM-AVIBACTAM ± METRONIDAZOLE COMPARED TO BEST AVAILABLE THERAPY (BAT) IN PEDIATRIC PARTICIPANTS 9 MONTHS TO LESS THAN 18 YEARS OF AGE WITH SERIOUS GRAM-NEGATIVE BACTERIAL INFECTIONS INCLUDING COMPLICATED INTRA-ABDOMINAL INFECTION
The purpose of this study is to evaluate how Aztreonam (ATM) and Avibactam (AVI) are processed in pediatric participants. This study also aims to understand participant safety and effects in pediatric participants.
The study is seeking participants who are:
- 9 months to less than 18 years of age
- Hospitalized
- Suspected/known to have a gram-negative infection
- Receiving intravenous (iv, given directly into a vein) antibiotics
- Being treated for complicated infections of various body parts that includes the abdomen, urinary tract, blood stream, and lungs.
- Participants will receive either ATM-AVI or best available therapy (BAT).
- Both therapies will be given through a vein.
- Participants with complicated abdominal infections will also receive iv Metronidazole (MTZ). Patients with cIAI and Cockayne Syndrome are excluded due to a risk of severe hepatotoxicity with the use of MTZ. - Participants on ATM-AVI treatment who have anaerobic infections will also receive iv MTZ at the study doctor's discretion.
- The iv dose of ATM-AVI will be based on the participant's weight and kidney function.
- The study doctor will determine the iv dose of BAT.
- During the first 2 study days, participants on ATM-AVI therapy will have 5 blood draws in small quantities.
- Starting on day 4, the study doctor will decide if participants may be switched to oral therapy.
- Participants will receive a maximum of 14 days of ATM-AVI treatment.
- After discharge from the hospital, 1 study visit may be required.
- Depending on the participant's response, the study duration will be from 33 to 50 days.
- The investigator will contact participants by phone 28 to 35 days after the last study treatment to check participants health status.
Read the detailed description
- Following informed consent, potential participants who are hospitalized, receiving IV antibiotics for less than 24 hours within 48 hours of randomization or failed antibiotic therapy for greater than 48 hours and have suspected/known gram-negative bacterial infections with a complex intra-abdominal infection (cIAI), complex urinary tract (cUTI), blood stream infection (BSI), hospital acquired pneumonia or ventilator associated pneumonia (HAP/VAP) will be screened.
- Although cultures are required, isolation of the causative pathogen is not a criteria for enrollment. - cUTI participants requiring systemic prophylactic antibiotics for any reason at screening are allowed to enter the study provided they discontinue this medication prior to first study drug dose.
- If the participant satisfies the inclusion and exclusion requirements, the participant will be randomly enrolled in a ratio of 3 iv ATM-AVI for each iv BAT.
- A total of 48 participants at approximately 33 sites will be randomized using interactive response technology (IRT).
- The study will be multicenter, international and open label with a single blinded observer assigned by each investigational site.
- There will be 4 cohorts with ages 12 to less than 18 years (Cohort 1), 6 to less than 12 years (Cohort 2), 2 to less than 6 years (Cohort 3) and 9 months to less than 2 years (Cohort 4).
- Each cohort will have 12 participants for a total of 48 participants.
- Cohorts 1 and 2 will be enrolled simultaneously. - - Cohort 3 will begin enrollment after the first 4 participants complete Cohort 2 and PK data and safety have been reviewed by the sponsor and an external data monitoring committee (DMC). Then ATM-AVI dose may be adjusted as needed.
- Cohort 4 will begin enrollment after the first 4 participants completed Cohort 3 and the PK data have been reviewed by the sponsor and the DMC. Then the ATM-AVI dose may be adjusted as needed.
- After 4 participants complete Cohort 4 the PK data will be review by the sponsor and DMC and then the ATM-AVI dose may be adjusted as needed.
- Enrollment will not be paused during the PK data reviews of the first 4 ATM-AVI participants in a cohort. If the ATM-AVI dose requires adjustment, the cohort 4 number will be increased to 20 with 15 receiving ATM-AVI and 5 BAT.
- All participants in the ATM-AVI group will receive an initial ATM-AVI loading dose and then maintenance doses every 6 or 8 hours depending on the participant's weight and kidney function.
- ATM-AVI will be infused over 3 hours.
- Those with cIAI will receive metronidazole (MTZ). Patients with cIAI and Cockayne Syndrome are excluded due to a risk of severe hepatotoxicity with the use of MTZ. - At the investigator's discretion MTZ will be administered to those with BSI, cUTI or HAP/VAP and an associated anaerobic infection.
- MTZ will be administered iv over 20 to 30 minutes starting.
- Optional gram-positive coverage with vancomycin, teicoplanin and linezolid is permitted. Daptomycin is only permitted for cIAI and BSI participants.
- Coverage with iv aminoglycoside is permitted for Pseudomonas aeruginosa.
- Concerning concomitant medications, participants with cUTI may not take prophylactic therapy during study drug treatment.
- Systemic antibiotics are not permitted unless the study drug failed, or it is for a remote site infection essential for participant's safety.
- Systemic iv antivirals are permitted.
- Systemic antifungals should be avoided unless indicated.
- Meropenem/carbapenem-type antibiotics cannot be given concomitantly with ATM-AVI.
- Probenecid and inhaled antibiotics are to be avoided from informed consent until the end of iv treatment (EOIV).
- Antibiotic peritoneal lavage is not permitted. Non-antibiotic lavage is permitted.
- The primary endpoints are pharmacokinetics (PK) and safety.
- Five PK micro-blood samples of at least 0.1 mL will be drawn. The initial 2 PK micro blood samples will be drawn at 2 hours and 5 hours after the first infusion. The next 3 PK micro-blood samples will be drawn at 15 minutes before, 5 hours and 5 3/4 hours after the 5th infusion or a later infusion.
- ATM and AVI clearance (CL), maximum (Cmax) and minimum (Cmin) venous blood concentration, area under the curve (AUC) and half-life (t1/2) will be analyzed.
- A blinded observer (BO), assigned by each investigational site, will clinically assess the participants every day.
- The BO will evaluate causality of all adverse events (AEs) and serious adverse events (SAEs) while the participant is in the hospital, within 24 hours of the end of iv study drug (EOIV), and within 48 hours of end of treatment for those switched to oral therapy.
- For the secondary endpoint of efficacy, the BO will clinically assess the test of cure (TOC) within 7 to 14 days of the last antibiotic treatment. Potential for liver function abnormalities and acute kidney injury will be specifically monitored in addition to standard of care assessments.
- Cure is defined as signs and symptoms improved with no further antimicrobial treatment required except for adjunctive gram-positive therapy or for Pseudomonas aeruginosa.
- In addition, for cIAI participants, no unplanned drainage or surgical intervention is necessary since the initial surgical procedure. Only for those switched to oral therapy before 14 days, improvement is afebrile with absence of new signs or symptoms and improvement of 1 or more symptoms or signs with no worsening of signs or symptoms.
- Failure is defined as death, requirement of antibiotics for the index infection, or discontinuation due to an AE(s). cIAI participants have additional failure criteria of requiring surgical intervention and/or have an infected post-surgical wound(s).
- Participant may choose to permanently discontinue and are free to discontinue treatment without further treatment prejudice. Possible reasons for permanent discontinuation are:
- Condition under investigation resolved prior to minimum treatment period
- AE or any other condition posing a risk to a participant or jeopardizing safety
- Investigator, national coordinators, medical monitor, and/or Sponsor decided it is in the best interest of the participant's safety
- Positive pregnancy test during the treatment period
- Absence of explanation for liver injury and/or increase in liver function tests or acute kidney toxicity
- Discontinuation of intervention does not represent withdrawal from the study and participants should remain in the study until the end of the study (EOS).
- Conditions
- Gram-negative Bacterial Infections
- Being tested
- ATM-AVI, BAT
- Keywords
- Gram-negative bacterial infections
- Medical subject headings
- Gram-Negative Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATM-AVIDrug
Also called aztreonam plus avibactam
A drug specifically designed to treat resistant gam-negative bacterial infections
BATDrug
Also called Best available therapy
BAT will be selected by the investigator and administered iv as appropriate for the selected drug(s)
| Study group | Role | What they receive |
|---|---|---|
| ATM-AVI | Experimental | ATM-AVI administered iv every 6 or 8 hours and dosed according to participant's weight and kidney function for up to 14 days depending on response. At the investigator's discretion, the participant may be switched to oral therapy after 3 days of iv ATM-AVI therapy Receives: Drug: ATM-AVI |
| Best available therapy (BAT) | Active comparator | BAT will be selected by the investigator and administered iv. At the investigator's discretion, the participant may be switched to oral therapy after 3 days of iv BAT Receives: Drug: BAT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Predicted Plasma Concentration (Cmax) of ATM and AVI
Cmax is the maximum plasma concentration of ATM and AVI as population pharmacokinetic (popPK) analysis predicts.
Measured: Up to 15 Days
Minimum Predicted Trough Plasma Concentration (Cmin) of ATM and AVI
Cmin is the minimum trough plasma concentration of ATM and AVI as popPK analysis predicts.
Measured: Up to 15 Days
Area under the Concentration-Time Curve (AUC) of ATM-AVI
AUC is a measure of the plasma concentration of ATM and AVI overtime as popPK analysis predicts.
Measured: Up to 15 Days
Plasma Decay Half-Life (t1/2)
Half-life is the time measured for the plasma concentration of ATM and AVI to decrease by one half as popPK analysis predicts.
Measured: Up to 15 Days
Apparent Clearance (CL)
ATM and AVI clearance is a quantitative measure of the rate at which ATM and AVI are removed from the blood (rate at which ATM and AVI are metabolized or eliminated by normal biological processes). Clearance obtained after intravenous infusion dose (apparent clearance) is influenced by the fraction of the dose absorbed.
Measured: Up to 15 Days
Proportion of Participants reporting Adverse Events (AE)
Proportion of participant AE reports of vital signs, physical examinations, and clinical laboratory tests overall and by age cohort. For each AE the last assessment made prior to the first dose of study drug will be defined as the baseline.
Measured: Baseline up to Day 50
Proportion of Participants reporting Serious Adverse Events (SAE)
Proportion of participant SAE reports of vital signs, physical examinations, and clinical laboratory tests overall and by age cohort. For each SAE the last assessment made prior to the first dose of study drug will be defined as the baseline.
Measured: Baseline up to Day 50
Proportion of Participants reporting AEs leading to discontinuation
Proportion of Participants reporting AEs leading to discontinuation from baseline. For each discontinuation the last assessment made prior to the first dose of study drug will be defined as the baseline
Measured: Baseline up to Day 50
Proportion of Participants reporting AEs resulting in death
Proportion of Participants reporting AE resulting in death from baseline. For each death the last assessment made prior to the first dose of study drug will be defined as the baseline
Measured: Baseline up to Day 50
Proportion of Participants reporting liver injury and acute kidney injury of ATM-AVI relative to Best Available Therapy (BAT)
Proportion of Participants reporting liver injury and acute kidney injury of ATM-AVI relative to Best Available Therapy (BAT) from baseline. For each report of liver and acute kidney injury the last assessment made prior to the first dose of study drug will be defined as the baseline
Measured: Baseline up to Day 50
Secondary outcomes (6)
Perentage of participants with favorable clinical response (CR) at end of iv study treatment (EOIV)
EOIV favorable CR is baseline signs and symptoms have improved such that with in 24hours after iv study treatment stopped, or premature discontinuation of the study drug or early withdrawal from the study no further antimicrobial treatment for the index infection is required. In addition, for cIAI participants, no unplanned drainage or surgical intervention is necessary since the initial procedure.
Measured: Up to 15 days after iv study drug treatment
Percentage of Participants With Favorable Clinical Response (CR) at End of Treatment (EOT)
EOT is only for those that were switched to oral therapy a favorable CR is baseline signs and symptoms have improved such that after study treatment, no further antimicrobial treatment for the index infection is required. In addition for cIAI participants, no unplanned drainage or surgical intervention is necessary since the initial procedure.
Measured: EOT within 48 hours after last dose of oral switch therapy or at time of premature discontinuation of study drug or early withdrawal from study
Percentage of Participants With Favorable Clinical Response (CR) at Test of Cure (TOC)
A TOC favorable CR is baseline signs and symptoms have improved such that after up to 14 days of study treatment, no further antimicrobial treatment for the index infection is required. In addition for cIAI participants, no unplanned drainage or surgical intervention is necessary since the initial procedure.
Measured: Up to 15 Days after last study treatment
Percentage of participants with Favorable Microbiological Response at end of iv study drug treatment (EOIV)
Eradication (or urine quantification <103 CFU/mL for cUTI participants) of causative pathogen from an appropriately obtained specimen at the site of infection and presumed eradication specific to cIAI and HAP/VAP participants when repeat culture of specimens were not performed or clinically indicated in a participant who had a clinical response of cure
Measured: EOIV within 24 hours after last iv study drug infusion
Percentage of Participants with Favorable Microbiological Response at End of Treatment (EOT)
Eradication (or urine quantification <103 CFU/mL for cUTI participants) of causative pathogen from an appropriately obtained specimen at the site of infection and presumed eradication specific to cIAI and HAP/VAP participants when repeat culture of specimens were not performed or clinically indicated in a participant who had a clinical response of cure in participants who were switched to oral therapy
Measured: EOT within 48 hours after last dose of oral switch therapy or at time of premature discontinuation of study drug or early withdrawal from study
Percentage of Participants with Favorable Microbiological Response at test of cure (TOC)
Eradication (or urine quantification <103 CFU/mL for cUTI participants) of causative pathogen from an appropriately obtained specimen at the site of infection and presumed eradication specific to cIAI and HAP/VAP participants when repeat culture of specimens were not performed or clinically indicated in a participant who had a clinical response of cure.
Measured: Up to 15 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2022
- Study start18 Apr 2023
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gram-negative Bacterial InfectionsStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, open-label, parallel study comparing ATM-AVI with or without metronidazole (MTZ) compared to BAT for the treatment of serious gram-negative bacterial infections. For every 3 participants assigned to ATM-AVI therapy one will be assigned to BAT.
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05639647
- Sponsor's protocol ID
- C3601008
- Other IDs
- 2022-501575-12-00
- Status last verified
- Jun 2026
- First submitted
- 24 Oct 2022
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PHASE 2A MULTICENTER, OBSERVER-BLINDED, RANDOMIZED 2 ARM STUDY TO INVESTIGATE PHARMACOKINETICS, SAFETY, TOLERABILITY AND EFFICACY OF INTRAVENOUS AZTREONAM-AVIBACTAM ± METRONIDAZOLE COMPARED TO BEST AVAILABLE THERAPY (BAT) IN PEDIATRIC PARTICIPANTS 9 MONTHS TO LESS THAN 18 YEARS OF AGE WITH SERIOUS GRAM-NEGATIVE BACTERIAL INFECTIONS INCLUDING COMPLICATED INTRA-ABDOMINAL INFECTION
- ClinicalTrials.gov ID
- NCT05639647
- Acronym / sponsor ID
- C3601008
- Conditions
- Gram-negative Bacterial Infections
- Keywords
- Gram-negative bacterial infections
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 18 Apr 2023 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 6 Dec 2022 (actual)
- Results
- Not posted in the source record
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 how Aztreonam (ATM) and Avibactam (AVI) are processed in pediatric participants. This study also aims to understand participant safety and effects in pediatric participants.
The study is seeking participants who are:
- 9 months to less than 18 years of age
- Hospitalized
- Suspected/known to have a gram-negative infection
- Receiving intravenous (iv, given directly into a vein) antibiotics
- Being treated for complicated infections of various body parts that includes the abdomen, urinary tract, blood stream, and lungs.
- Participants will receive either ATM-AVI or best available therapy (BAT).
- Both therapies will be given through a vein.
- Participants with complicated abdominal infections will also receive iv Metronidazole (MTZ). Patients with cIAI and Cockayne Syndrome are excluded due to a risk of severe hepatotoxicity with the use of MTZ. - Participants on ATM-AVI treatment who have anaerobic infections will also receive iv MTZ at the study doctor's discretion.
- The iv dose of ATM-AVI will be based on the participant's weight and kidney function.
- The study doctor will determine the iv dose of BAT.
- During the first 2 study days, participants on ATM-AVI therapy will have 5 blood draws in small quantities.
- Starting on day 4, the study doctor will decide if participants may be switched to oral therapy.
- Participants will receive a maximum of 14 days of ATM-AVI treatment.
- After discharge from the hospital, 1 study visit may be required.
- Depending on the participant's response, the study duration will be from 33 to 50 days.
- The investigator will contact participants by phone 28 to 35 days after the last study treatment to check participants health status.
Detailed description
- Following informed consent, potential participants who are hospitalized, receiving IV antibiotics for less than 24 hours within 48 hours of randomization or failed antibiotic therapy for greater than 48 hours and have suspected/known gram-negative bacterial infections with a complex intra-abdominal infection (cIAI), complex urinary tract (cUTI), blood stream infection (BSI), hospital acquired pneumonia or ventilator associated pneumonia (HAP/VAP) will be screened.
- Although cultures are required, isolation of the causative pathogen is not a criteria for enrollment. - cUTI participants requiring systemic prophylactic antibiotics for any reason at screening are allowed to enter the study provided they discontinue this medication prior to first study drug dose.
- If the participant satisfies the inclusion and exclusion requirements, the participant will be randomly enrolled in a ratio of 3 iv ATM-AVI for each iv BAT.
- A total of 48 participants at approximately 33 sites will be randomized using interactive response technology (IRT).
- The study will be multicenter, international and open label with a single blinded observer assigned by each investigational site.
- There will be 4 cohorts with ages 12 to less than 18 years (Cohort 1), 6 to less than 12 years (Cohort 2), 2 to less than 6 years (Cohort 3) and 9 months to less than 2 years (Cohort 4).
- Each cohort will have 12 participants for a total of 48 participants.
- Cohorts 1 and 2 will be enrolled simultaneously. - - Cohort 3 will begin enrollment after the first 4 participants complete Cohort 2 and PK data and safety have been reviewed by the sponsor and an external data monitoring committee (DMC). Then ATM-AVI dose may be adjusted as needed.
- Cohort 4 will begin enrollment after the first 4 participants completed Cohort 3 and the PK data have been reviewed by the sponsor and the DMC. Then the ATM-AVI dose may be adjusted as needed.
- After 4 participants complete Cohort 4 the PK data will be review by the sponsor and DMC and then the ATM-AVI dose may be adjusted as needed.
- Enrollment will not be paused during the PK data reviews of the first 4 ATM-AVI participants in a cohort. If the ATM-AVI dose requires adjustment, the cohort 4 number will be increased to 20 with 15 receiving ATM-AVI and 5 BAT.
- All participants in the ATM-AVI group will receive an initial ATM-AVI loading dose and then maintenance doses every 6 or 8 hours depending on the participant's weight and kidney function.
- ATM-AVI will be infused over 3 hours.
- Those with cIAI will receive metronidazole (MTZ). Patients with cIAI and Cockayne Syndrome are excluded due to a risk of severe hepatotoxicity with the use of MTZ. - At the investigator's discretion MTZ will be administered to those with BSI, cUTI or HAP/VAP and an associated anaerobic infection.
- MTZ will be administered iv over 20 to 30 minutes starting.
- Optional gram-positive coverage with vancomycin, teicoplanin and linezolid is permitted. Daptomycin is only permitted for cIAI and BSI participants.
- Coverage with iv aminoglycoside is permitted for Pseudomonas aeruginosa.
- Concerning concomitant medications, participants with cUTI may not take prophylactic therapy during study drug treatment.
- Systemic antibiotics are not permitted unless the study drug failed, or it is for a remote site infection essential for participant's safety.
- Systemic iv antivirals are permitted.
- Systemic antifungals should be avoided unless indicated.
- Meropenem/carbapenem-type antibiotics cannot be given concomitantly with ATM-AVI.
- Probenecid and inhaled antibiotics are to be avoided from informed consent until the end of iv treatment (EOIV).
- Antibiotic peritoneal lavage is not permitted. Non-antibiotic lavage is permitted.
- The primary endpoints are pharmacokinetics (PK) and safety.
- Five PK micro-blood samples of at least 0.1 mL will be drawn. The initial 2 PK micro blood samples will be drawn at 2 hours and 5 hours after the first infusion. The next 3 PK micro-blood samples will be drawn at 15 minutes before, 5 hours and 5 3/4 hours after the 5th infusion or a later infusion.
- ATM and AVI clearance (CL), maximum (Cmax) and minimum (Cmin) venous blood concentration, area under the curve (AUC) and half-life (t1/2) will be analyzed.
- A blinded observer (BO), assigned by each investigational site, will clinically assess the participants every day.
- The BO will evaluate causality of all adverse events (AEs) and serious adverse events (SAEs) while the participant is in the hospital, within 24 hours of the end of iv study drug (EOIV), and within 48 hours of end of treatment for those switched to oral therapy.
- For the secondary endpoint of efficacy, the BO will clinically assess the test of cure (TOC) within 7 to 14 days of the last antibiotic treatment. Potential for liver function abnormalities and acute kidney injury will be specifically monitored in addition to standard of care assessments.
- Cure is defined as signs and symptoms improved with no further antimicrobial treatment required except for adjunctive gram-positive therapy or for Pseudomonas aeruginosa.
- In addition, for cIAI participants, no unplanned drainage or surgical intervention is necessary since the initial surgical procedure. Only for those switched to oral therapy before 14 days, improvement is afebrile with absence of new signs or symptoms and improvement of 1 or more symptoms or signs with no worsening of signs or symptoms.
- Failure is defined as death, requirement of antibiotics for the index infection, or discontinuation due to an AE(s). cIAI participants have additional failure criteria of requiring surgical intervention and/or have an infected post-surgical wound(s).
- Participant may choose to permanently discontinue and are free to discontinue treatment without further treatment prejudice. Possible reasons for permanent discontinuation are:
- Condition under investigation resolved prior to minimum treatment period
- AE or any other condition posing a risk to a participant or jeopardizing safety
- Investigator, national coordinators, medical monitor, and/or Sponsor decided it is in the best interest of the participant's safety
- Positive pregnancy test during the treatment period
- Absence of explanation for liver injury and/or increase in liver function tests or acute kidney toxicity
- Discontinuation of intervention does not represent withdrawal from the study and participants should remain in the study until the end of the study (EOS).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
- Model description
- Randomized, open-label, parallel study comparing ATM-AVI with or without metronidazole (MTZ) compared to BAT for the treatment of serious gram-negative bacterial infections. For every 3 participants assigned to ATM-AVI therapy one will be assigned to BAT.
| Arm | Type | Receives |
|---|---|---|
| ATM-AVI | Experimental | Drug: ATM-AVIATM-AVI administered iv every 6 or 8 hours and dosed according to participant's weight and kidney function for up to 14 days depending on response. At the investigator's discretion, the participant may be switched to oral therapy after 3 days of iv ATM-AVI therapy |
| Best available therapy (BAT) | Active comparator | Drug: BATBAT will be selected by the investigator and administered iv. At the investigator's discretion, the participant may be switched to oral therapy after 3 days of iv BAT |
Who may qualify
- Ages
- 9 months to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Participants must meet the following key inclusion criteria to be eligible for enrollment into the study:
- Participants ≥9 months to <18 years of age at Screening; Female (post-menarchal) participants must have a negative serum/urine pregnancy test (β hCG sensitivity ≥25 mIU/mL).
- Suspected/confirmed cIAI, cUTI, HAP/VAP, or BSI with gram-negative pathogens.
- Require hospitalization and IV antibiotic treatment.
Key exclusion criteria (11 listed)
- Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
- Gram-negative species not expected to respond to ATM AVI ≤14 days.
- Pregnant or breastfeeding; fertile male/female unwilling/unable to use effective contraception for at ≥7 days (males) or ≥28 days (females) after last ATM-AVI infusion.
- Microbiologically known or high likelihood of monomicrobial infection with a gram-positive organism, lung abscess, pleural empyema, or post-obstructive pneumonia, lung or heart transplant.
- Received >24 hours of systemic antibiotics during the 48 hours before randomization unless participant has documented treatment failure after at least 48 hours of antibiotic therapy.
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 |
|---|---|---|
| ATM-AVIAlso: aztreonam plus avibactamA drug specifically designed to treat resistant gam-negative bacterial infections | Drug | ATM-AVI |
| BATAlso: Best available therapyBAT will be selected by the investigator and administered iv as appropriate for the selected drug(s) | Drug | Best available therapy (BAT) |
Primary outcome
Maximum Predicted Plasma Concentration (Cmax) of ATM and AVI
Time frame: Up to 15 Days
Cmax is the maximum plasma concentration of ATM and AVI as population pharmacokinetic (popPK) analysis predicts.
Minimum Predicted Trough Plasma Concentration (Cmin) of ATM and AVI
Time frame: Up to 15 Days
Cmin is the minimum trough plasma concentration of ATM and AVI as popPK analysis predicts.
Area under the Concentration-Time Curve (AUC) of ATM-AVI
Time frame: Up to 15 Days
AUC is a measure of the plasma concentration of ATM and AVI overtime as popPK analysis predicts.
Plasma Decay Half-Life (t1/2)
Time frame: Up to 15 Days
Half-life is the time measured for the plasma concentration of ATM and AVI to decrease by one half as popPK analysis predicts.
Apparent Clearance (CL)
Time frame: Up to 15 Days
ATM and AVI clearance is a quantitative measure of the rate at which ATM and AVI are removed from the blood (rate at which ATM and AVI are metabolized or eliminated by normal biological processes). Clearance obtained after intravenous infusion dose (apparent clearance) is influenced by the fraction of the dose absorbed.
Proportion of Participants reporting Adverse Events (AE)
Time frame: Baseline up to Day 50
Proportion of participant AE reports of vital signs, physical examinations, and clinical laboratory tests overall and by age cohort. For each AE the last assessment made prior to the first dose of study drug will be defined as the baseline.
Proportion of Participants reporting Serious Adverse Events (SAE)
Time frame: Baseline up to Day 50
Proportion of participant SAE reports of vital signs, physical examinations, and clinical laboratory tests overall and by age cohort. For each SAE the last assessment made prior to the first dose of study drug will be defined as the baseline.
Proportion of Participants reporting AEs leading to discontinuation
Time frame: Baseline up to Day 50
Proportion of Participants reporting AEs leading to discontinuation from baseline. For each discontinuation the last assessment made prior to the first dose of study drug will be defined as the baseline
Proportion of Participants reporting AEs resulting in death
Time frame: Baseline up to Day 50
Proportion of Participants reporting AE resulting in death from baseline. For each death the last assessment made prior to the first dose of study drug will be defined as the baseline
Proportion of Participants reporting liver injury and acute kidney injury of ATM-AVI relative to Best Available Therapy (BAT)
Time frame: Baseline up to Day 50
Proportion of Participants reporting liver injury and acute kidney injury of ATM-AVI relative to Best Available Therapy (BAT) from baseline. For each report of liver and acute kidney injury the last assessment made prior to the first dose of study drug will be defined as the baseline
6 secondary outcomes
Perentage of participants with favorable clinical response (CR) at end of iv study treatment (EOIV)
Time frame: Up to 15 days after iv study drug treatment
Percentage of Participants With Favorable Clinical Response (CR) at End of Treatment (EOT)
Time frame: EOT within 48 hours after last dose of oral switch therapy or at time of premature discontinuation of study drug or early withdrawal from study
Percentage of Participants With Favorable Clinical Response (CR) at Test of Cure (TOC)
Time frame: Up to 15 Days after last study treatment
Percentage of participants with Favorable Microbiological Response at end of iv study drug treatment (EOIV)
Time frame: EOIV within 24 hours after last iv study drug infusion
Percentage of Participants with Favorable Microbiological Response at End of Treatment (EOT)
Time frame: EOT within 48 hours after last dose of oral switch therapy or at time of premature discontinuation of study drug or early withdrawal from study
Percentage of Participants with Favorable Microbiological Response at test of cure (TOC)
Time frame: Up to 15 Days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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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.
Pfizer CT.gov Call Center study director
Pfizer
23 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ATM-AVI and BAT in people with Gram-negative Bacterial Infections, run by Pfizer at 23 sites in 8 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 11 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: looking for participants now, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Spain, United States, China, India, Taiwan and 3 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Pfizer CT.gov Call Center (1-800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Predicted Plasma Concentration (Cmax) of ATM and AVI (time frame: Up to 15 Days). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Jul 2026.