Clinical trial NCT01506271: Study of the Safety, Tolerability, and Efficacy of Relebactam (MK-7655) + Imipenem/Cilastatin Versus Imipenem/Cilastatin Alone to Treat Complicated Intra-Abdominal Infection [cIAI] (MK-7655-004)
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 Intra-Abdominal Infection [cIAI]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Intra-abdominal Infections
Keywords: Complicated Intra-abdominal Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-01-09
Enrollment: 351
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy, safety and tolerability of adding 125 mg or 250 mg doses of relebactam (MK-7655) to imipenem/cilastatin in adults 18 years or older with Complicated Intra-Abdominal Infection (cIAI). The primary hypothesis is that the relebactam + imipenem/cilastatin treatment regimen is non-inferior to treatment with imipenem/cilastatin alone with respect to the percentage of participants with a favorable clinical response at completion of intravenous (IV) study therapy.


Eligibility criteria: Inclusion Criteria:

* Clinically suspected and/or bacteriologically documented cIAI requiring hospitalization and treatment with IV antibiotic therapy.
* Enrolled intraoperatively or postoperatively on the basis of operative findings OR enrolled preoperatively on the basis of compelling preoperative clinical findings.

Exclusion Criteria:

* Infection which should be managed by Staged Abdominal Repair (STAR) or open abdomen technique.
* Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 30.
* Any amount of effective antibiotic therapy after obtaining the 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 \>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 β-lactam agents.
* History of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to other β-lactamase inhibitors (e.g., tazobactam, sulbactam, clavulanic acid).
* History of a seizure disorder (requiring ongoing treatment with anticonvulsive therapy or prior treatment with anti-convulsive therapy in the last 3 years).
* Currently being treated with valproic acid or has used 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, breastfeeding, or plans to breast feed within 1 month of completion of the study.
* Participant in whom a response to IV study therapy 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.
* cIAI due to a confirmed fungal pathogen.
* Currently receiving immunosuppressive therapy, including use of high-dose corticosteroids.
* Prior recipient of a renal transplantation.
* Estimated or actual creatinine clearance of \<50 mL/minute.
* 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 to the patient.
* Laboratory abnormalities as specified in protocol.
* 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 the trial.

Primary outcomes:
measure: Percentage of Participants With a Favorable Clinical Response at Completion of IV Study Therapy
timeFrame: 4 to 14 days post initiation of intravenous (IV) study therapy (up to postrandomization Day 14)
measure: Percentage of Participants With an Elevated Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) Laboratory Values That Are Greater Than or Equal to 5X the Upper Limit of Normal (ULN)
timeFrame: Up to 14 days following completion of all study therapy (up to Day 28)
measure: Percentage of Participants With Elevated AST or ALT Laboratory Values >= 3X the ULN, Total Bilirubin >= 2X the ULN, and Alkaline Phosphatase Values < 2X the ULN
timeFrame: Up to 14 days following completion of all study therapy (up to Day 28)
measure: Percentage of Participants With Any Adverse Event (AE)
timeFrame: Up to 14 days following completion of all study therapy (up to Day 28)
measure: Percentage of Participants With Any Serious Adverse Event (SAE)
timeFrame: Up to 14 days following completion of all study therapy (up to Day 28)
measure: Percentage of Participants With Any Drug-related AE
timeFrame: Up to 14 days following completion of all study therapy (up to Day 28)
measure: Percentage of Participants With Any Drug-related SAE
timeFrame: Up to 42 days following completion of all study therapy (up to Day 56)
measure: Percentage of Participants Who Discontinued IV Study Therapy Due to an AE
timeFrame: Up to 14 days post initiation of IV study therapy (up to 14 days)
measure: Percentage of Participants Who Discontinued IV Study Therapy Due to a Drug-related AE
timeFrame: Up to 14 days post initiation of IV study therapy (up to 14 days)
measure: Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group
timeFrame: Up to 42 days following completion of all study therapy (up to Day 56)
measure: Percentage of Participants With Predefined Limit of Change (PDLC) With Incidence of >= 4 Participants in One Treatment Group
timeFrame: Up to 42 days following completion of all study therapy (up to Day 56)
measure: Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group
timeFrame: Up to 42 days following completion of all study therapy (up to Day 56)
Secondary outcomes:
measure: Percentage of Participants With a Favorable Clinical Response at Completion of IV Study Therapy in Participants Who Have Imipenem-resistant, Gram-negative cIAI Infections.
timeFrame: 4 to 14 days post initiation of IV study therapy (up to postrandomization day 14).
measure: Percentage of Participants With a Favorable Clinical Response at Early Follow-up
timeFrame: Up to 9 days following completion of all study therapy (up to Day 23)
measure: Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy
timeFrame: Up to 14 days post initiation of IV study therapy (up to postrandomization day 14)
measure: Percentage of Participants With a Favorable Microbiological Response at Early Follow-up
timeFrame: Up to 9 days following completion of all study therapy (up to Day 23)
measure: Percentage of Participants With a Favorable Clinical Response at Late Follow-up
timeFrame: Up to 42 days following completion of all study therapy (up to Day 56)
measure: Percentage of Participants With a Favorable Microbiological Response at Late Follow-up
timeFrame: Up to 42 days following completion of all study therapy (up to Day 56)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Lucasti C, Vasile L, Sandesc D, Venskutonis D, McLeroth P, Lala M, Rizk ML, Brown ML, Losada MC, Pedley A, Kartsonis NA, Paschke A. Phase 2, Dose-Ranging Study of Relebactam with Imipenem-Cilastatin in Subjects with Complicated Intra-abdominal Infection. Antimicrob Agents Chemother. 2016 Sep 23;60(10):6234-43. doi: 10.1128/AAC.00633-16. Print 2016 Oct.