Evidence map›Paper›PMID 31400759›Full record

Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2020

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.

Johann Motsch, Cláudia Murta de Oliveira, Viktor Stus, Iftihar Köksal, Olexiy Lyulko, Helen W Boucher, Keith S Kaye, Thomas M File, Michelle L Brown, Ireen Khan and 8 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02452047 (A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Clinical Trial to Estimate the Efficacy and Safety of Imipenem/Cilastatin/Relebactam), which is not on this map. Cited by 207 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
207citing papers in PubMed, 7 pooled it
15.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02452047 phase3completednot on this map

A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Clinical Trial to Estimate the Efficacy and Safety of Imipenem/Cilastatin/Relebactam (MK-7655A) Versus Colistimethate Sodium + Imipenem/Cilastatin in Subjects With Imipenem-Resistant Bacterial Infection

TypeinterventionalSponsorMerck Sharp & Dohme LLCRan2015 to 2017Enrolled50ConditionsBacterial InfectionsArmsImipenem+Cilastatin/Relebactam, Colistimethate sodium (CMS), Imipenem+Cilastatin, Placebo to CMS
3 · Its place in the literature

Who cites it

207 citing papers in PubMed, 7 syntheses or guidelines pooled it, 385 citations in OpenAlex.

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  16. Addressing therapeutic options for KPC-3-producing ST307-Antimicrobial agents and chemotherapy · 2026
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147 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 8 institutions in 4 countries.

Johann MotschUniversitätsklinikum Heidelberg, Germany.
Cláudia Murta de OliveiraSanta Casa de Misericórdia, Belo Horizonte, Brazil.
Viktor StusDnipropetrovsk Medical Academy, Dnipro, Ukraine.
Iftihar KöksalKaradeniz Technical University School of Medicine, Trabzon, Turkey.
Olexiy LyulkoDepartment of Urology, Zaporozhye State Medical University, Zaporozhye, Ukraine.
Helen W BoucherTufts Medical Center, Boston, Massachusetts.
Keith S KayeUniversity of Michigan, Ann Arbor, Michigan.
Thomas M FileSumma Health, Akron, Ohio.
Michelle L BrownMerck & Co., Inc., Kenilworth, New Jersey.
Ireen KhanMerck & Co., Inc., Kenilworth, New Jersey.
Jiejun DuMerck & Co., Inc., Kenilworth, New Jersey.
Hee-Koung JoengMerck & Co., Inc., Kenilworth, New Jersey.
Robert W TippingMerck & Co., Inc., Kenilworth, New Jersey.
Angela AggreyMerck & Co., Inc., Kenilworth, New Jersey.
Katherine YoungMerck & Co., Inc., Kenilworth, New Jersey.
Nicholas A KartsonisMerck & Co., Inc., Kenilworth, New Jersey.
Joan R ButtertonMerck & Co., Inc., Kenilworth, New Jersey.
Amanda PaschkeMerck & Co., Inc., Kenilworth, New Jersey.
Merck & Co., Inc., Rahway, NJ, USA (United States) · USDnipropetrovsk State Medical Academy · UAHeidelberg University · DEKaradeniz Technical University · TRSumma Health System · USTufts Medical Center · USUniversity of Michigan–Ann Arbor · USZaporizhia State Medical University · UA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe β-lactamase inhibitor relebactam can restore imipenem activity against imipenem-nonsusceptible gram-negative pathogens. We evaluated imipenem/relebactam for treating imipenem-nonsusceptible infections.

methodsRandomized, controlled, double-blind, phase 3 trial. Hospitalized patients with hospital-acquired/ventilator-associated pneumonia, complicated intraabdominal infection, or complicated urinary tract infection caused by imipenem-nonsusceptible (but colistin- and imipenem/relebactam-susceptible) pathogens were randomized 2:1 to 5-21 days imipenem/relebactam or colistin+imipenem. Primary endpoint: favorable overall response (defined by relevant endpoints for each infection type) in the modified microbiologic intent-to-treat (mMITT) population (qualifying baseline pathogen and ≥1 dose study treatment). Secondary endpoints: clinical response, all-cause mortality, and treatment-emergent nephrotoxicity. Safety analyses included patients with ≥1 dose study treatment.

resultsThirty-one patients received imipenem/relebactam and 16 colistin+imipenem. Among mITT patients (n = 21 imipenem/relebactam, n = 10 colistin+imipenem), 29% had Acute Physiology and Chronic Health Evaluation II scores >15, 23% had creatinine clearance <60 mL/min, and 35% were aged ≥65 years. Qualifying baseline pathogens: Pseudomonas aeruginosa (77%), Klebsiella spp. (16%), other Enterobacteriaceae (6%). Favorable overall response was observed in 71% imipenem/relebactam and 70% colistin+imipenem patients (90% confidence interval [CI] for difference, -27.5, 21.4), day 28 favorable clinical response in 71% and 40% (90% CI, 1.3, 51.5), and 28-day mortality in 10% and 30% (90% CI, -46.4, 6.7), respectively. Serious adverse events (AEs) occurred in 10% of imipenem/relebactam and 31% of colistin+imipenem patients, drug-related AEs in 16% and 31% (no drug-related deaths), and treatment-emergent nephrotoxicity in 10% and 56% (P = .002), respectively.

conclusionsImipenem/relebactam is an efficacious and well-tolerated treatment option for carbapenem-nonsusceptible infections. CLINICAL TRIALS REGISTRATION: NCT02452047.

Indexed as

Bacterial InfectionsImipenemAnti-Bacterial AgentsAzabicyclo CompoundsColistinHumansMicrobial Sensitivity TestsAnti-Bacterial AgentsAzabicyclo CompoundsColistinImipenemrelebactamcarbapenem resistantcIAIcUTIKPCnosocomial pneumonia

Identifiers

PMID31400759
PMCPMC7156774
OpenAlexW2968244461

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.