Phase 3
Completed N=50
Efficacy and Safety of Imipenem+Cilastatin/Relebactam (MK-7655A) Versus Colistimethate Sodium+Imipenem+Cilastatin in Imipenem-Resistant Bacterial Infection (MK-7655A-013)
Source: ClinicalTrials.gov NCT02452047 ↗Enrolled (actual)
50
Serious AEs
24.0%
Results posted
Oct 2018
Primary outcomePrimary: Percentage of Participants With Favorable Overall Response (FOR) — 71.4; 70.0 Percentage of Participants
◆ Published Evidence
Highly cited
405citations · ~68 / year
RESTORE-IMI 1: A Multicenter, Randomized, Double-blind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections.
Summary
The study will evaluate the efficacy and safety of imipenem+cilastatin/relebactam (MK-7655A) versus colistimethate sodium+imipenem+cilastatin in the treatment of imipenem-resistant bacterial infections. Infections evaluated in the study will be hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), complicated intra-abdominal infection (cIAI), and complicated urinary tract infection (cUTI).
Linked Publications (3)
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RESTORE-IMI 1: A Multicenter, Randomized, Double-blind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections.
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Comparison of Treatment Outcomes between Analysis Populations in the RESTORE-IMI 1 Phase 3 Trial of Imipenem-Cilastatin-Relebactam versus Colistin plus Imipenem-Cilastatin in Patients with Imipenem-Nonsusceptible Bacterial Infections.
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Evaluation of Renal Safety Between Imipenem/Relebactam and Colistin Plus Imipenem in Patients With Imipenem-Nonsusceptible Bacterial Infections in the Randomized, Phase 3 RESTORE-IMI 1 Study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Favorable Overall Response (FOR) |
71.4; 70.0 | — |
| PRIMARY Percentage of Participants With ≥1 Adverse Events (AEs) |
71.0; 81.3; 100.0 | — |
| PRIMARY Percentage of Participants With ≥1 Serious Adverse Events (SAEs) |
9.7; 31.3; 100.0 | — |
| PRIMARY Percentage of Participants With ≥1 Drug-Related AEs |
16.1; 31.3; 33.3 | — |
| PRIMARY Percentage of Participants With ≥1 Drug-Related SAEs |
0.0; 0.0; 33.3 | — |
| PRIMARY Percentage of Participants Discontinuing From Study Therapy Due to ≥1 AEs |
0.0; 18.8; 33.3 | — |
| PRIMARY Percentage of Participants Discontinuing From Study Therapy Due to ≥1 Drug-Related AEs |
0.0; 12.5; 33.3 | — |
| PRIMARY Analysis of Specific AEs With an Incidence of ≥4 Participants in a Treatment Group |
12.9; 12.5; 0.0; 25.0 | — |
| PRIMARY Percentage of Participants With ≥1 Events of Clinical Interest (ECI) |
0.0; 12.5; 0.0; 12.5 | 0.047 sig |
| SECONDARY Percentage of Participants With ≥1 Events of Treatment-Emergent Nephrotoxicity |
10.3; 56.3 | 0.002 sig |
| SECONDARY Percentage of Participants With Favorable Clinical Response (FCR) at Day 28 |
71.4; 40.0 | — |
| SECONDARY Percentage of Participants With All-cause Mortality Up to Day 28 |
9.5; 30.0 | — |
| SECONDARY Percentage of Participants With FCR on Therapy (OTX) |
81.0; 40.0 | — |
| SECONDARY Percentage of Participants With FCR at End of Therapy (EOT) |
90.5; 60.0 | — |
| SECONDARY Percentage of Participants With FCR at EFU |
81.0; 50.0 | — |
| SECONDARY Percentage of cUTI Participants With Favorable Microbiological Response (FMR) at OTX |
100.0; 100.0 | — |
| SECONDARY Percentage of cUTI Participants With FMR at EOT |
100.0; 100.0 | — |
| SECONDARY Percentage of cUTI Participants With FMR at EFU |
72.7; 100.0 | — |
Eligibility Criteria
Inclusion Criteria
- Hospitalization that requires treatment with IV antibiotic therapy for a new, persistent or progressing bacterial infection involving at least 1 of 3 primary infection types (HABP, VABP, cIAI, or cUTI)
- Positive culture data from the primary infection-site specimen collected within 1 week of study entry. At least one of the suspected causative pathogens from the specimen meets all of the following: 1) identified as a Gram-negative bacterium, 2) culture-confirmed imipenem resistance (and colistin resistance for Group 3 only), 3) culture-confirmed susceptibility to imipenem/relebactam and to colistin (for Groups 1 and 2 only)
- Not of reproductive potential, or of reproductive potential and agrees to avoid becoming pregnant or impregnating a partner by complying with one of the following: 1) practice abstinence, or 2) use of acceptable contraception during heterosexual activity
Exclusion Criteria
- Concurrent infection (endocarditis, osteomyelitis, meningitis, prosthetic joint infection, disseminated fungal infection, or active pulmonary tuberculosis) that would interfere with evaluation of the response to the study antibiotics
- Received treatment with any form of systemic colistin for >24 hours within 72 hours before initiation of study drug (for Groups 1 and 2 only)
- HABP or VABP caused by an obstructive process
- cUTI which meets any of the following: 1) complete obstruction of any portion of the urinary tract, 2) known ileal loop, 3) intractable vesico-ureteral reflux, 4) presence of an indwelling urinary catheter which cannot be removed at study entry
- History of serious allergy, hypersensitivity, or any serious reaction to listed antibiotics (per-protocol)
- Female who is pregnant or is expecting to conceive (or a male partner of a female who is expecting to conceive), is breastfeeding, or plans to breastfeed before completion of the study
- Anticipated treatment with any of the following during the study: valproic acid or divalproex sodium, or concomitant systemic (e.g. IV, oral or inhaled) antimicrobial agents with known Gram-negative bacterial coverage
- Currently undergoing hemodialysis or peritoneal dialysis
- Participated or anticipates participating in any other clinical study involving administration of investigational medication up to 30 days before screening or during the course of the trial
Data sourced from ClinicalTrials.gov (NCT02452047) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.