Evidence map›Paper›PMID 34251506›Full record

Trial reportIntensive care medicine2021

Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial.

Yaseen M Arabi, Anthony C Gordon, Lennie P G Derde, Alistair D Nichol, Srinivas Murthy, Farah Al Beidh, Djillali Annane, Lolowa Al Swaidan, Abi Beane, Richard Beasley and 58 more

Open access · bronzeAbstract readRandomized Controlled TrialAdaptive Clinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Intensive care medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 8 pooled it
5.4field-weighted citation impact, top 3% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 8 syntheses or guidelines pooled it, 96 citations in OpenAlex.

  1. Pooled it
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  3. Antiviral drug treatment for nonsevere COVID-19: a systematic review and network meta-analysis.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2022
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  12. Simvastatin in Critically Ill Patients with Covid-19.The New England journal of medicine · 2023
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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

68 authors at 20 institutions in 11 countries.

Yaseen M ArabiIntensive Care Department, Ministry of the National Guard-Health Affairs, ICU 1425, P.O. Box 22490, Riyadh, 11426, Kingdom of Saudi Arabia. arabi@ngha.med.sa.ORCID http://orcid.org/0000-0001-5735-6241
Anthony C GordonDivision of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London, UK.
Lennie P G DerdeIntensive Care Center, University Medical Center Utrecht, Utrecht, The Netherlands.
Alistair D NicholUniversity College Dublin Clinical Research Centre At St Vincents University Hospital, Dublin, Ireland.
Srinivas MurthyDepartment of Pediatrics, University of British Columbia, Vancouver, Canada.
Farah Al BeidhDivision of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London, UK.
Djillali AnnaneDepartment of Intensive Care, Hôpital Raymond Poincaré (APHP), 92380, Garches, France.
Lolowa Al SwaidanKing Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia.
Abi BeaneNuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
Richard BeasleyMedical Research Institute of New Zealand, Wellington, New Zealand.
Lindsay R BerryBerry Consultants, Austin, TX, USA.
Zahra BhimaniSt. Michael's Hospital Unity Health Toronto, Toronto, Canada.
Marc J M BontenJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
Charlotte A BradburyFaculty of Health Sciences, University of Bristol, Bristol, UK.
Frank M BrunkhorstAnesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
Meredith BuxtonGlobal Coalition for Adaptive Research, San Francisco, CA, USA.
Adrian BuzgauMonash University, Melbourne, Australia.
Allen ChengMonash University, Melbourne, Australia.
Menno De JongDepartment of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
Michelle A DetryBerry Consultants, Austin, TX, USA.
Eamon J DuffyInfectious Disease, Auckland City Hospital, Auckland, New Zealand.
Lise J EstcourtNHS Blood and Transplant, Oxford, UK.
Mark FitzgeraldBerry Consultants, Austin, TX, USA.
Rob FowlerUniversity of Toronto, Toronto, ON, Canada.
Timothy D GirardUPMC Health System, Pittsburgh, PA, USA.
Ewan C GoligherInterdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada.
Herman GoossensUniversity of Antwerp, Wilrijk, Belgium.
Rashan HaniffaNational Intensive Care Surveillance-Mahidol Oxford Research Unit, Colombo, Sri Lanka.
Alisa M HigginsThe Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia.
Thomas E HillsMedical Research Institute of New Zealand, Wellington, New Zealand.
Christopher M HorvatUPMC Health System, Pittsburgh, PA, USA.
David T HuangUPMC Health System, Pittsburgh, PA, USA.
Andrew J KingUniversity of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Francois LamontagneUniversité de Sherbrooke, Sherbrooke, Canada.
Patrick R LawlerUniversity of Toronto, Toronto, ON, Canada.
Roger LewisBerry Consultants, Austin, TX, USA.
Kelsey LinstrumUPMC Health System, Pittsburgh, PA, USA.
Edward LittonIntensive Care Unit, Fiona Stanley Hospital, Perth, Australia.
Elizabeth LorenziBerry Consultants, Austin, TX, USA.
Salim MalakoutiComputer Science, University of Pittsburgh, Pittsburgh, PA, USA.
Daniel F McAuleyWellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK.
Anna McGlothlinBerry Consultants, Austin, TX, USA.
Shay McguinnessMedical Research Institute of New Zealand, Wellington, New Zealand.
Bryan J McVerryUPMC Health System, Pittsburgh, PA, USA.
Stephanie K MontgomeryUPMC Health System, Pittsburgh, PA, USA.
Susan C MorpethMicrobiology Laboratory, Middlemore Hospital, Auckland, New Zealand.
Paul R MounceyClinical Trials Unit, Intensive Care National Audit and Research Centre, London, UK.
Katrina OrrPharmacy Department, Fiona Stanley Hospital, Perth, Australia.
Rachael ParkeMedical Research Institute of New Zealand, Wellington, New Zealand.
Jane C ParkerThe Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia.
Asad E PatanwalaSchool of Pharmacy, University of Sydney, Sydney, Australia.
Kathryn M RowanIntensive Care National Audit and Research Centre (ICNARC), London, UK.
Marlene S SantosSt. Michael's Hospital Unity Health Toronto, Toronto, Canada.
Christina T SaundersBerry Consultants, Austin, TX, USA.
Christopher W SeymourUPMC Health System, Pittsburgh, PA, USA.
Manu Shankar-HariCritical Care Medicine, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Steven Y C TongVictorian Infectious Diseases Service, The Royal Melbourne Hospital, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Alexis F TurgeonDivision of Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Laval University, Quebec City, QC, Canada.
Anne M TurnerMedical Research Institute of New Zealand, Wellington, New Zealand.
Frank Leo Van de VeerdonkDepartment of Internal Medicine, Radboudumc, Nijmegen, The Netherlands.
Ryan ZarychanskiCritical Care Department, University of Manitoba, Winnipeg, Canada.
Cameron GreenThe Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia.
Scott BerryBerry Consultants, Austin, TX, USA.
John C MarshallSt. Michael's Hospital Unity Health Toronto, Toronto, Canada.
Colin McArthurDepartment of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand.
Derek C AngusUPMC Health System, Pittsburgh, PA, USA.
Steven A WebbThe Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia.
REMAP-CAP Investigators
University of Pittsburgh · USBerry & Associates (United States) · USSt. Michael's Hospital · CAAustralian and New Zealand Intensive Care Society · AUUniversity College Dublin · IEAuckland City Hospital · NZImperial College Healthcare NHS Trust · GBSt John of God Subiaco Hospital · AUMedical Research Institute of New Zealand · NZUniversity Medical Center Utrecht · NLUniversity of Manitoba · CASt John of God Hospital · AUUniversity of British Columbia · CAMiddlemore Hospital · NZUtrecht University · NLAuckland District Health Board · NZIntensive Care National Audit & Research Centre · GBQueen's University Belfast · GBKing Saud bin Abdulaziz University for Health Sciences · SAUniversity Health Network · CA

Funding

Translational Training Program in Pulmonary Biology and MedicineT32HL007563 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Melanie Koenigshoff · 1985 to 2026
$12.3M
Sepsis subtypes: biology, treatment, and bedside applicationR35GM119519 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Christopher W. Seymour · 2016 to 2026
$4.9M
The Gut Microbiome in Carbapenem-Resistant Enterobacteriaceae Colonization, Persistence, Infection, and Tolerance after Lung or Liver TransplantationK23AI154546 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HAIDAR, GHADY · 2021 to 2025
$896k
NHLBI NIH HHS T32 HL007563NIGMS NIH HHS R35 GM119519
6 · The paper itself

Abstract

purposeTo study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19).

methodsCritically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable.

resultsWe randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (- 1 to 15), 0 (- 1 to 9) and-1 (- 1 to 7), respectively, compared to 6 (- 1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥ 99.0%), and high probabilities of harm (98.0%, 99.9% and > 99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively).

conclusionAmong critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.

Indexed as

COVID-19 Drug TreatmentRitonavirAdultAntiviral AgentsBayes TheoremCritical IllnessDrug CombinationsHumansHydroxychloroquineLopinavirSARS-CoV-2Antiviral AgentsDrug CombinationsHydroxychloroquineLopinavirRitonavirAdaptive platform trialCOVID-19HydroxychloroquineIntensive careLopinavir-ritonavirPandemicPneumonia

Identifiers

PMID34251506
PMCPMC8274471
OpenAlexW3182129217

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.