Evidence map›Paper›PMID 27503659›Full record

Trial reportAntimicrobial agents and chemotherapy2016

Phase 2, Dose-Ranging Study of Relebactam with Imipenem-Cilastatin in Subjects with Complicated Intra-abdominal Infection.

Christopher Lucasti, Liviu Vasile, Dorel Sandesc, Donatas Venskutonis, Patrick McLeroth, Mallika Lala, Matthew L Rizk, Michelle L Brown, Maria C Losada, Alison Pedley and 2 more

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

Trial report in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01506271 (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]), which is not on this map. Cited by 87 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed, 5 pooled it
9.2field-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.

NCT01506271 phase2completednot on this map

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]

TypeinterventionalSponsorMerck Sharp & Dohme LLCRan2012 to 2014Enrolled351ConditionsIntra-abdominal InfectionsArmsRelebactam 250 mg, Relebactam 125 mg, Imipenem/cilastatin, Matching placebo to relebactam
3 · Its place in the literature

Who cites it

87 citing papers in PubMed, 5 syntheses or guidelines pooled it, 178 citations in OpenAlex.

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27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 3 countries.

Christopher LucastiSouth Jersey Infectious Disease, Somers Point, New Jersey, USA.
Liviu VasileUniversity of Medicine & Pharmacy, Craiova, Romania.
Dorel SandescUniversity of Medicine & Pharmacy, Timisoara, Romania.
Donatas VenskutonisLithuanian University of Health Sciences, Medical Academy, Kaunas, Lithuania.
Patrick McLerothCovance Inc., Princeton, New Jersey, USA.
Mallika LalaMerck & Co., Inc., Kenilworth, New Jersey, USA.
Matthew L RizkMerck & Co., Inc., Kenilworth, New Jersey, USA.
Michelle L BrownMerck & Co., Inc., Kenilworth, New Jersey, USA.
Maria C LosadaMerck & Co., Inc., Kenilworth, New Jersey, USA.
Alison PedleyMerck & Co., Inc., Kenilworth, New Jersey, USA.
Nicholas A KartsonisMerck & Co., Inc., Kenilworth, New Jersey, USA.
Amanda PaschkeMerck & Co., Inc., Kenilworth, New Jersey, USA amanda.paschke@merck.com.
Merck & Co., Inc., Rahway, NJ, USA (United States) · USCovance (United States) · USLithuanian University of Health Sciences · LTUniversity of Medicine and Pharmacy of Craiova · ROVictor Babeș University of Medicine and Pharmacy Timișoara · RO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Relebactam (REL [MK-7655]) is a novel class A/C β-lactamase inhibitor intended for use with imipenem for the treatment of Gram-negative bacterial infections. REL restores imipenem activity against some resistant strains of Klebsiella and Pseudomonas In this multicenter, double-blind, controlled trial (NCT01506271), subjects who were ≥18 years of age with complicated intra-abdominal infection were randomly assigned (1:1:1) to receive 250 mg REL, 125 mg REL, or placebo, each given intravenously (i.v.) with 500 mg imipenem-cilastatin (IMI) every 6 h (q6h) for 4 to 14 days. The primary efficacy endpoint was the proportion of microbiologically evaluable (ME) subjects with a favorable clinical response at discontinuation of i.v. therapy (DCIV). A total of 351 subjects were randomized, 347 (99%) were treated, and 255 (73%) were ME at DCIV (55% male; mean age, 49 years). The most common diagnoses were complicated appendicitis (53%) and complicated cholecystitis (17%). Thirty-six subjects (13%) had imipenem-resistant Gram-negative infections at baseline. Both REL doses plus IMI were generally well tolerated and demonstrated safety profiles similar to that of IMI alone. Clinical response rates at DCIV were similar in subjects who received 250 mg REL plus IMI (96.3%) or 125 mg REL plus IMI (98.8%), and both were noninferior to IMI alone (95.2%; one-sided P < 0.001). The treatment groups were also similar with respect to clinical response at early and late follow-up and microbiological response at all visits. Pharmacokinetic/pharmacodynamic simulations show that imipenem exposure at the proposed dose of 500 mg IMI with 250 mg REL q6h provides coverage of >90% of carbapenem-resistant bacterial strains.

Indexed as

AdolescentAdultAgedAged, 80 and overAnti-Bacterial AgentsAzabicyclo CompoundsBacterial InfectionsCilastatinCilastatin, Imipenem Drug CombinationDouble-Blind MethodDrug CombinationsDrug Therapy, CombinationFemaleHumansImipenemIntraabdominal InfectionsAnti-Bacterial AgentsAzabicyclo CompoundsCilastatinCilastatin, Imipenem Drug CombinationDrug CombinationsImipenemrelebactam

Identifiers

PMID27503659
PMCPMC5038313
OpenAlexW2505961383

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.