Imipenem/Relebactam/Cilastatin Versus Piperacillin/Tazobactam for Treatment of Participants With Bacterial Pneumonia (MK-7655A-014)
Summary
This study aims to compare treatment with a fixed-dose combination (FDC) of imipenem/relebactam/cilastatin (IMI/REL) with a FDC of piperacillin/tazobactam (PIP/TAZ) in participants with hospital-acquired or ventilator-associated bacterial pneumonia (HABP or VAPB, respectively). The primary hypothesis is that IMI/REL is non-inferior to PIP/TAZ in the incidence rate of all-cause mortality.
Timeline
- Start
- 2015-11-24
- Primary completion
- 2019-04-03
- Completion
- 2019-04-03
Outcome
Met primary endpoint
paper Imipenem/cilastatin/relebactam was noninferior (P < .001) to piperacillin/tazobactam for both endpoints: day 28 all-cause mortality was 15.9% with imipenem/cilastatin/relebactam and 21.3% PMID 32785589 ↗
release “today announced that the pivotal Phase 3 RECARBRIO™ (imipenem 500 mg, cilastatin 500 mg, and relebactam 250 mg) RESTORE-IMI 2 trial met its primary endpoint.” merck.com ↗
release “RESTORE-IMI 2 trial met its primary endpoint” merck.com ↗
release “demonstrated noninferiority of RECARBRIO compared to piperacillin and tazobactam (PIP/TAZ), the active comparator, in the primary and key secondary endpoints of the study” merck.com ↗
Publications
- Patel M, Nieddu G, DeRyke CA, Young K, Chen LF, Paschke A, Rizk ML, Gheyas F. Imipenem/cilastatin/relebactam dosing regimen justification using exposure-efficacy analyses in participants with hospital-acquired bacterial pneumonia or ventilator-associated bacterial pneumonia in the RESTORE-IMI 2 phase 3 study. Antimicrob Agents Chemother. 2026 Mar 4;70(3):e0131325. doi: 10.1128/aac.01313-25. Epub 2026 Jan 26.
- Martin-Loeches I, Shorr AF, Kollef MH, Du J, Losada MC, Paschke A, DeRyke CA, Wong M, Jensen EH, Chen LF. Participant- and Disease-Related Factors as Independent Predictors of Treatment Outcomes in the RESTORE-IMI 2 Clinical Trial: A Multivariable Regression Analysis. Open Forum Infect Dis. 2023 May 4;10(6):ofad225. doi: 10.1093/ofid/ofad225. eCollection 2023 Jun.
- Patel M, Bellanti F, Daryani NM, Noormohamed N, Hilbert DW, Young K, Kulkarni P, Copalu W, Gheyas F, Rizk ML. Population pharmacokinetic/pharmacodynamic assessment of imipenem/cilastatin/relebactam in patients with hospital-acquired/ventilator-associated bacterial pneumonia. Clin Transl Sci. 2022 Feb;15(2):396-408. doi: 10.1111/cts.13158. Epub 2021 Oct 27.
- Titov I, Wunderink RG, Roquilly A, Rodriguez Gonzalez D, David-Wang A, Boucher HW, Kaye KS, Losada MC, Du J, Tipping R, Rizk ML, Patel M, Brown ML, Young K, Kartsonis NA, Butterton JR, Paschke A, Chen LF. A Randomized, Double-blind, Multicenter Trial Comparing Efficacy and Safety of Imipenem/Cilastatin/Relebactam Versus Piperacillin/Tazobactam in Adults With Hospital-acquired or Ventilator-associated Bacterial Pneumonia (RESTORE-IMI 2 Study). Clin Infect Dis. 2021 Dec 6;73(11):e4539-e4548. doi: 10.1093/cid/ciaa803.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Cilastatin | Small molecule | 500 mg | Intravenous |
| Subject | IMIPENEM ANHYDROUS | Small molecule | 500 mg | Intravenous |
| Comparator | Piperacillin | Small molecule | 4000 mg | — |
| Subject | Relebactam | Small molecule | 250 mg | Intravenous |
| Comparator | Tazobactam | Small molecule | 500 mg | — |
| Background | Linezolid | Other / unclassified | 600 mg | Intravenous |