Urinary Tract InfectionsPhase 2NCT01505634
Safety, Tolerability, and Efficacy of MK-7655 (Relebactam) + Imipenem/Cilastatin Versus Imipenem/Cilastatin Alone for Treating Complicated Urinary Tract Infection (cUTI) (MK-7655-003)
A Phase 2 study testing Relebactam 250 mg, Relebactam 125 mg and imipenem/cilastatin 500 mg in people with Urinary Tract Infections and Pyelonephritis, run by Merck Sharp & Dohme LLC.
Trial summary
The purpose of this study is to evaluate the efficacy, safety and tolerability of adding 125 mg or 250 mg doses of MK-7655 (relebactam) to imipenem/cilastatin in adults 18 years or older with complicated urinary tract infection (cUTI). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urinary Tract Infections, Pyelonephritis
- What is being tested?
- Relebactam 250 mg, Relebactam 125 mg and imipenem/cilastatin 500 mg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 302 participants
- Where
- No sites listed yet
- Study dates
- 16 May 2012to 28 Jul 2015
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinically suspected and/or bacteriologically documented cUTI or acute
- pyelonephritis judged by the investigator to be serious (requiring hospitalization and treatment with IV antibiotic therapy)
- Pyuria, determined by a midstream clean-catch (MSCC) or catheterized
- (indwelling or straight catheter) urine specimen with greater than or equal to 10 white blood cells (WBCs) per high-power field (hpf) on standard examination of urine sediment or greater than or equal to 10 WBCs/mm3 in unspun urine
- One positive urine culture within 48 hours of enrollment
Who cannot join
- Complete obstruction of any portion of the urinary tract (requiring a
- permanent indwelling urinary catheter or instrumentation), a known ileal loop, or intractable vesico-ureteral reflux
- A temporary indwelling urinary catheter is in place and cannot be removed at study entry.
- Perinephric or intrarenal abscess or known or suspected prostatitis
- Uncomplicated UTI
- Any history of recent accidental trauma to the pelvis or urinary tract
Show all 35Show fewer
- Any amount of effective antibiotic therapy after obtaining the urine culture for admission to this study and prior to the administration of the first dose of IV study therapy
- An infection which has been treated with greater than 24 hours of systemic antibiotic therapy known to be effective against the presumed or documented etiologic pathogen(s) within the 72-hour period immediately prior to consideration for entry into the study
- History of serious allergy, hypersensitivity (e.g., anaphylaxis), or any
- serious reaction to carbapenem antibiotics, any cephalosporins, penicillins, or other beta (β)-lactam agents
- History of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to other beta-lactam inhibitors (e.g., tazobactam, sulbactam, clavulanic acid)
- History of a seizure disorder
- Currently being treated with valproic acid or has received treatment with
- valproic acid in the 2 weeks prior to screening.
- Rapidly progressive or terminal illness unlikely to survive the approximately 6 to 8 week study period
- Pregnant or expecting to conceive, breast feeding, or plans to breast feed
- during the study
- A response to all study therapy (IV study therapy or subsequent oral
- ciprofloxacin) within the timeframe of treatment specified in this protocol is
- considered unlikely.
- Concurrent infection that would interfere with evaluation of response to
- the study antibiotics
- Need for concomitant systemic antimicrobial agents in addition to those
- designated in the various study treatment groups (use of vancomycin, daptomycin, or linezolid is allowed for certain infections)
- cUTI due to a confirmed fungal pathogen
- Currently receiving immunosuppressive therapy, including use of high-dose
- corticosteroids
- Prior recipient of a renal transplantation
- Laboratory abnormalities as specified in protocol
- History of any other illness that, in the opinion of the investigator, might
- confound the results of the study or pose additional risk in administering the study drug
- Currently participating in, or has participated in, any other clinical study
- involving the administration of investigational or experimental medication (not
- licensed by regulatory agencies) at the time of presentation or during the previous 30 days prior to screening or is anticipated to participate in such a clinical study during the course of this trial
- Estimated or actual creatinine clearance of <5 mL/minute, or is currently undergoing hemodialysis
About this study
Official title: A Phase II, Randomized, Active Comparator-Controlled Clinical Trial to Study the Safety, Tolerability, and Efficacy of MK-7655 + Imipenem/Cilastatin Versus Imipenem/Cilastatin Alone in Patients With Complicated Urinary Tract Infection (cUTI)
The purpose of this study is to evaluate the efficacy, safety and tolerability of adding 125 mg or 250 mg doses of MK-7655 (relebactam) to imipenem/cilastatin in adults 18 years or older with complicated urinary tract infection (cUTI). The primary hypothesis is that the relebactam + imipenem/cilastatin treatment regimen is non-inferior to imipenem/cilastatin with respect to the proportion of participants with a favorable microbiological response at completion of intravenous (IV) study therapy.
- Conditions
- Urinary Tract Infections, Pyelonephritis
- Being tested
- Relebactam 250 mg, Relebactam 125 mg, imipenem/cilastatin 500 mg, Placebo to relebactam, Ciprofloxacin
- Keywords
- Relebactam; MK-7655; Imipenem; Urinary Tract Infections; Pyelonephritis; Urologic Diseases; beta-Lactamase Inhibitors; Anti-Bacterial and Anti-Infective Agent
- Medical subject headings
- Urinary Tract Infections, Pyelonephritis, Urologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Relebactam 250 mgDrug
Also called MK-7655
Participants randomized to receive relebactam 250 mg will be administered a 250 mg dose of relebactam IV in a blinded fashion once every 6 hours with each dose infused over a 30-minute interval.
Relebactam 125 mgDrug
Also called MK-7655
Participants randomized to receive relebactam 125 mg will be administered a 125 mg dose of relebactam IV in a blinded-treatment fashion once every 6 hours with each dose infused over a 30-minute interval.
imipenem/cilastatin 500 mgDrug
Also called PRIMAXIN®, TIENAM®
A 500 mg dose of imipenem/cilastatin will be administered IV in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval.
Placebo to relebactamDrug
Participants randomized to receive imipenem/cilastatin alone will receive a placebo-matching infusion of IV normal saline (0.9%) once every 6 hours.
CiprofloxacinDrug
After at least 96 hours of IV treatment, participants may be switched, at the discretion of the investigator, to 500 mg ciprofloxacin, administered orally, twice daily
| Study group | Role | What they receive |
|---|---|---|
| Relebactam 250 mg with imipenem/cilastatin | Experimental | Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days. Receives: Drug: Relebactam 250 mg; Drug: imipenem/cilastatin 500 mg; Drug: Ciprofloxacin |
| Relebactam 125 mg with imipenem/cilastatin | Experimental | Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days. Receives: Drug: Relebactam 125 mg; Drug: imipenem/cilastatin 500 mg; Drug: Ciprofloxacin |
| Relebactam placebo with imipenem/cilastatin | Placebo comparator | Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days. Receives: Drug: imipenem/cilastatin 500 mg; Drug: Placebo to relebactam; Drug: Ciprofloxacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy
Microbiological response (MR) was assessed based on results of bacterial cultures obtained at completion of IV study medication relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the Microbiologically Evaluable (ME) population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
Measured: At time of last IV dose of study drug (up to post-randomization day 14)
Percentage of Participants With an Elevated Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) Laboratory Value That Was Greater Than or Equal to 5 Times the Upper Limit of Normal (ULN)
All randomized participants who received ≥1 dose of study treatment had AST and ALT levels measured up to 14 days following completion of all study medication. Participants who had 2 confirmed elevations of either AST or ALT that were 5 times ULN or greater were recorded.
Measured: Up to 14 days following completion of all study therapy (up to 28 days)
Percentage of Participants With Elevated AST or ALT Laboratory Values ≥ 3 Times the ULN, as Well as Elevated Total Bilirubin ≥ 2 Times the ULN, and Alkaline Phosphatase Values That Were < 2 Times the ULN
All randomized participants who received ≥1 dose of study treatment had AST, ALT, total bilirubin, and Alkaline Phosphatase (ALP) levels measured up to 14 days following completion of all study medication. Participants who had elevations of AST or ALT that were ≥3 times ULN, total bilirubin measurements that were ≥2 times ULN and, at the same time, an ALP measurement of < 2X ULN were recorded.
Measured: Up to 14 days following completion of all study therapy (up to 28 days)
Percentage of Participants With at Least 1 Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.
Measured: Up to 14 days following completion of all study therapy (up to 28 days)
Percentage of Participants With Any Serious Adverse Event (SAE)
A SAE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event.
Measured: Up to 14 days following completion of all study therapy (up to 28 days)
Percentage of Participants With Any Drug-related AE
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. A drug-related (DR) AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product that the investigator determined to be possibly, probably, or definitely related to the treatment.
Measured: Up to 14 days following completion of all study therapy (up to 28 days)
Percentage of Participants With a Drug-related SAE
A serious, drug-related (DR) AE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event. The SAE was determined to be possibly, probably, or definitely related to the treatment by the investigator.
Measured: Up to 42 days following completion of all study therapy (up to 56 days)
Percentage of Participants Who Discontinued IV Study Therapy Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a pre-existing condition temporally associated with the use of the product was also an AE.
Measured: Up to 14 days
Percentage of Participants Who Discontinued IV Study Therapy Due to a Drug-related AE
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. A drug-related AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product that the investigator determined to be possibly, probably, or definitely related to the treatment.
Measured: Up to 14 days
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. Analysis includes specific adverse events with an incidence of ≥4 participants in one treatment group or system organ class.
Measured: Up to 14 days following completion of all study therapy (up to 28 days)
Secondary outcomes (6)
Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy Who Had Imipenem-resistant, Gram-negative cUTI Infections.
Microbiological response was assessed based on results of bacterial cultures obtained at completion of IV study medication relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the Microbiologically Evaluable (ME) population that included participants with a urine culture confirmed to be positive for imipenem-resistant gram-negative or anaerobic infections at baseline. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
Measured: At time of last IV dose of study drug (up to post-randomization day 14)
Percentage of Participants With a Favorable Microbiological Response at Early Follow-up
Microbiological response was assessed based on results of bacterial cultures obtained up to 9 days following completion of all study medication (IV and oral) relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
Measured: Up to 9 days following completion of all study IV and oral therapy (up to Day 23)
Percentage of Participants With a Favorable Clinical Response at Completion of IV Study Therapy
Clinical response was assessed as favorable (cured or improved) or unfavorable (failure) relative to baseline. Response determination was based on physical findings including fever (or history of fever), chills or rigors (accompanied by fever), flank pain, costovertebral angle tenderness, dysuria, urinary urgency, urinary frequency, suprapubic or pelvic pain, nausea, or vomiting. Clinical response was assessed in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI.
Measured: At time of last IV dose of study drug (up to postrandomization day 14)
Percentage of Participants With a Favorable Clinical Response at Early Follow-up
Clinical response was assessed as favorable (cured or improved) or unfavorable (failure) relative to baseline. Response determination was based on physical findings including fever (or history of fever), chills or rigors (accompanied by fever), flank pain, costovertebral angle tenderness, dysuria, urinary urgency, urinary frequency, suprapubic or pelvic pain, nausea, or vomiting. Clinical response was assessed in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI.
Measured: Up to 9 days following completion of all study IV and oral therapy (up to Day 23)
Percentage of Participants With a Favorable Clinical Response at Late Follow-up
Clinical response was assessed as favorable (cured or improved) or unfavorable (failure) relative to baseline. Response determination was based on physical findings including fever (or history of fever), chills or rigors (accompanied by fever), flank pain, costovertebral angle tenderness, dysuria, urinary urgency, urinary frequency, suprapubic or pelvic pain, nausea, or vomiting. Clinical response was assessed in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI.
Measured: Up to 42 days following completion of all study IV and oral therapy (up to Day 56)
Percentage of Participants With a Favorable Microbiological Response at Late Follow-up
Microbiological response was assessed based on results of bacterial cultures obtained up to 42 days following completion of all study medication (IV and oral) relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
Measured: Up to 42 days following completion of all study IV and oral therapy (up to Day 56)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2012 (estimated)
- Study start16 May 2012
- Primary completion28 Jul 2015
- Study completion28 Jul 2015
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 (1)Papers the sponsor has linked to this study.
- Other trials for Urinary Tract InfectionsStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe 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
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 302 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01505634
- Sponsor's protocol ID
- 7655-003
- Other IDs
- 2011-005707-32, MK-7655-003
- Status last verified
- Apr 2019
- First submitted
- 4 Jan 2012
- Last updated
- 24 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Sims M, Mariyanovski V, McLeroth P, Akers W, Lee YC, Brown ML, Du J, Pedley A, Kartsonis NA, Paschke A. Prospective, randomized, double-blind, Phase 2 dose-ranging study comparing efficacy and safety of imipenem/cilastatin plus relebactam with imipenem/cilastatin alone in patients with complicated urinary tract infections. J Antimicrob Chemother. 2017 Sep 1;72(9):2616-2626. doi: 10.1093/jac/dkx139.
PubMed 28575389
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized, Active Comparator-Controlled Clinical Trial to Study the Safety, Tolerability, and Efficacy of MK-7655 + Imipenem/Cilastatin Versus Imipenem/Cilastatin Alone in Patients With Complicated Urinary Tract Infection (cUTI)
- ClinicalTrials.gov ID
- NCT01505634
- Acronym / sponsor ID
- 7655-003
- Conditions
- Urinary Tract Infections, Pyelonephritis
- Keywords
- Relebactam; MK-7655; Imipenem; Urinary Tract Infections; Pyelonephritis; Urologic Diseases; beta-Lactamase Inhibitors; Anti-Bacterial and Anti-Infective Agent
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 302 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 16 May 2012 (actual)
- Primary completion
- 28 Jul 2015 (actual)
- Study completion
- 28 Jul 2015 (actual)
- First posted
- 6 Jan 2012 (estimated)
- Results
- Posted 24 May 2019
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 efficacy, safety and tolerability of adding 125 mg or 250 mg doses of MK-7655 (relebactam) to imipenem/cilastatin in adults 18 years or older with complicated urinary tract infection (cUTI). The primary hypothesis is that the relebactam + imipenem/cilastatin treatment regimen is non-inferior to imipenem/cilastatin with respect to the proportion of participants with a favorable microbiological response at completion of intravenous (IV) study therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Relebactam 250 mg with imipenem/cilastatin | Experimental | Drug: Relebactam 250 mg, Drug: imipenem/cilastatin 500 mg, Drug: CiprofloxacinRelebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days. |
| Relebactam 125 mg with imipenem/cilastatin | Experimental | Drug: Relebactam 125 mg, Drug: imipenem/cilastatin 500 mg, Drug: CiprofloxacinRelebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days. |
| Relebactam placebo with imipenem/cilastatin | Placebo comparator | Drug: imipenem/cilastatin 500 mg, Drug: Placebo to relebactam, Drug: CiprofloxacinMatching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Clinically suspected and/or bacteriologically documented cUTI or acute
- pyelonephritis judged by the investigator to be serious (requiring hospitalization and treatment with IV antibiotic therapy)
- Pyuria, determined by a midstream clean-catch (MSCC) or catheterized
- (indwelling or straight catheter) urine specimen with greater than or equal to 10 white blood cells (WBCs) per high-power field (hpf) on standard examination of urine sediment or greater than or equal to 10 WBCs/mm3 in unspun urine
- One positive urine culture within 48 hours of enrollment
Key exclusion criteria (35 listed)
- Complete obstruction of any portion of the urinary tract (requiring a
- permanent indwelling urinary catheter or instrumentation), a known ileal loop, or intractable vesico-ureteral reflux
- A temporary indwelling urinary catheter is in place and cannot be removed at study entry.
- Perinephric or intrarenal abscess or known or suspected prostatitis
- Uncomplicated UTI
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 |
|---|---|---|
| Relebactam 250 mgAlso: MK-7655Participants randomized to receive relebactam 250 mg will be administered a 250 mg dose of relebactam IV in a blinded fashion once every 6 hours with each dose infused over a 30-minute interval. | Drug | Relebactam 250 mg with imipenem/cilastatin |
| Relebactam 125 mgAlso: MK-7655Participants randomized to receive relebactam 125 mg will be administered a 125 mg dose of relebactam IV in a blinded-treatment fashion once every 6 hours with each dose infused over a 30-minute interval. | Drug | Relebactam 125 mg with imipenem/cilastatin |
| imipenem/cilastatin 500 mgAlso: PRIMAXIN®, TIENAM®A 500 mg dose of imipenem/cilastatin will be administered IV in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval. | Drug | Relebactam 125 mg with imipenem/cilastatin, Relebactam 250 mg with imipenem/cilastatin, Relebactam placebo with imipenem/cilastatin |
| Placebo to relebactamParticipants randomized to receive imipenem/cilastatin alone will receive a placebo-matching infusion of IV normal saline (0.9%) once every 6 hours. | Drug | Relebactam placebo with imipenem/cilastatin |
| CiprofloxacinAfter at least 96 hours of IV treatment, participants may be switched, at the discretion of the investigator, to 500 mg ciprofloxacin, administered orally, twice daily | Drug | Relebactam 125 mg with imipenem/cilastatin, Relebactam 250 mg with imipenem/cilastatin, Relebactam placebo with imipenem/cilastatin |
Primary outcome
Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy
Time frame: At time of last IV dose of study drug (up to post-randomization day 14)
Microbiological response (MR) was assessed based on results of bacterial cultures obtained at completion of IV study medication relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the Microbiologically Evaluable (ME) population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
Percentage of Participants With an Elevated Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) Laboratory Value That Was Greater Than or Equal to 5 Times the Upper Limit of Normal (ULN)
Time frame: Up to 14 days following completion of all study therapy (up to 28 days)
All randomized participants who received ≥1 dose of study treatment had AST and ALT levels measured up to 14 days following completion of all study medication. Participants who had 2 confirmed elevations of either AST or ALT that were 5 times ULN or greater were recorded.
Percentage of Participants With Elevated AST or ALT Laboratory Values ≥ 3 Times the ULN, as Well as Elevated Total Bilirubin ≥ 2 Times the ULN, and Alkaline Phosphatase Values That Were < 2 Times the ULN
Time frame: Up to 14 days following completion of all study therapy (up to 28 days)
All randomized participants who received ≥1 dose of study treatment had AST, ALT, total bilirubin, and Alkaline Phosphatase (ALP) levels measured up to 14 days following completion of all study medication. Participants who had elevations of AST or ALT that were ≥3 times ULN, total bilirubin measurements that were ≥2 times ULN and, at the same time, an ALP measurement of < 2X ULN were recorded.
Percentage of Participants With at Least 1 Adverse Event (AE)
Time frame: Up to 14 days following completion of all study therapy (up to 28 days)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.
Percentage of Participants With Any Serious Adverse Event (SAE)
Time frame: Up to 14 days following completion of all study therapy (up to 28 days)
A SAE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event.
Percentage of Participants With Any Drug-related AE
Time frame: Up to 14 days following completion of all study therapy (up to 28 days)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. A drug-related (DR) AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product that the investigator determined to be possibly, probably, or definitely related to the treatment.
Percentage of Participants With a Drug-related SAE
Time frame: Up to 42 days following completion of all study therapy (up to 56 days)
A serious, drug-related (DR) AE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event. The SAE was determined to be possibly, probably, or definitely related to the treatment by the investigator.
Percentage of Participants Who Discontinued IV Study Therapy Due to an AE
Time frame: Up to 14 days
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a pre-existing condition temporally associated with the use of the product was also an AE.
Percentage of Participants Who Discontinued IV Study Therapy Due to a Drug-related AE
Time frame: Up to 14 days
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. A drug-related AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product that the investigator determined to be possibly, probably, or definitely related to the treatment.
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group
Time frame: Up to 14 days following completion of all study therapy (up to 28 days)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. Analysis includes specific adverse events with an incidence of ≥4 participants in one treatment group or system organ class.
6 secondary outcomes
Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy Who Had Imipenem-resistant, Gram-negative cUTI Infections.
Time frame: At time of last IV dose of study drug (up to post-randomization day 14)
Percentage of Participants With a Favorable Microbiological Response at Early Follow-up
Time frame: Up to 9 days following completion of all study IV and oral therapy (up to Day 23)
Percentage of Participants With a Favorable Clinical Response at Completion of IV Study Therapy
Time frame: At time of last IV dose of study drug (up to postrandomization day 14)
Percentage of Participants With a Favorable Clinical Response at Early Follow-up
Time frame: Up to 9 days following completion of all study IV and oral therapy (up to Day 23)
Percentage of Participants With a Favorable Clinical Response at Late Follow-up
Time frame: Up to 42 days following completion of all study IV and oral therapy (up to Day 56)
Percentage of Participants With a Favorable Microbiological Response at Late Follow-up
Time frame: Up to 42 days following completion of all study IV and oral therapy (up to Day 56)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28575389Sims M, Mariyanovski V, McLeroth P, Akers W, Lee YC, Brown ML, Du J, Pedley A, Kartsonis NA, Paschke A. Prospective, randomized, double-blind, Phase 2 dose-ranging study comparing efficacy and safety of imipenem/cilastatin plus relebactam with imipenem/cilastatin alone in patients with complicated urinary tract infections. J Antimicrob Chemother. 2017 Sep 1;72(9):2616-2626. doi: 10.1093/jac/dkx139.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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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. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Relebactam 250 mg, Relebactam 125 mg and imipenem/cilastatin 500 mg in people with Urinary Tract Infections and Pyelonephritis, run by Merck Sharp & Dohme LLC.
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 5 inclusion and 35 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 24 May 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 24 May 2019). 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?
Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy (time frame: At time of last IV dose of study drug (up to post-randomization day 14)). 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?
On the ClinicalTrials.gov record for NCT01505634, which also lists 1 linked publication.
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 24 May 2019.