Conv. Plasma
Nigella Sativa

All HCQ studies
Meta analysis
study COVID-19 treatment researchHCQHCQ (more..)
Melatonin Meta
Metformin Meta
Antihistamines Meta
Azvudine Meta Molnupiravir Meta
Bromhexine Meta
Budesonide Meta
Colchicine Meta Nigella Sativa Meta
Conv. Plasma Meta Nitazoxanide Meta
Curcumin Meta Paxlovid Meta
Famotidine Meta Quercetin Meta
Favipiravir Meta Remdesivir Meta
Fluvoxamine Meta Thermotherapy Meta
Hydroxychlor.. Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

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

Arabi et al., Intensive Care Medicine, REMAP-CAP, NCT02735707
Jul 2021  
  Source   PDF   All Studies   Meta AnalysisMeta
Mortality -44% Improvement Relative Risk HCQ  REMAP-CAP  ICU PATIENTS  RCT Is very late treatment with HCQ beneficial for COVID-19? RCT 402 patients in multiple countries Higher mortality with HCQ (p=0.015) Arabi et al., Intensive Care Medicine, Jul 2021 FavorsHCQ Favorscontrol 0 0.5 1 1.5 2+
HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
*, now with p < 0.00000000001 from 411 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments.
Very late stage RCT with 50 ICU patients treated with HCQ, 255 lopinavir-ritonavir patients, and 27 combined therapy patients, showing higher mortality with all treatments.
Authors do not report results for patients in the "moderate" state.
"Moderate" was hospitalized patients not receiving organ support in the ICU.
Severe was patients requiring organ support in the ICU.
Note: the longer term followup results reported in Higgins et al. are included in meta analysis.
risk of death, 44.5% higher, RR 1.44, p = 0.01, treatment 17 of 49 (34.7%), control 106 of 353 (30.0%), adjusted per study, inverted to make RR<1 favor treatment, odds ratio converted to relative risk, multivariable.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Arabi et al., 12 Jul 2021, Randomized Controlled Trial, multiple countries, peer-reviewed, 1 author, trial NCT02735707 (history) (REMAP-CAP).
This PaperHCQAll
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, Lindsay R Berry, Zahra Bhimani, Marc J M Bonten, Charlotte A Bradbury, Frank M Brunkhorst, Meredith Buxton, Adrian Buzgau, Allen Cheng, Menno De Jong, Michelle A Detry, Eamon J Duffy, Lise J Estcourt, Mark Fitzgerald, Rob Fowler, Timothy D Girard, Ewan C Goligher, Herman Goossens, Rashan Haniffa, Alisa M Higgins, Thomas E Hills, Christopher M Horvat, David T Huang, Andrew J King, Francois Lamontagne, Patrick R Lawler, Roger Lewis, Kelsey Linstrum, Edward Litton, Elizabeth Lorenzi, Salim Malakouti, Daniel F Mcauley, Anna Mcglothlin, Shay Mcguinness, Bryan J Mcverry, Stephanie K Montgomery, Susan C Morpeth, Paul R Mouncey, Katrina Orr, Rachael Parke, Jane C Parker, Asad E Patanwala, Kathryn M Rowan, Marlene S Santos, Christina T Saunders, Christopher W Seymour, Manu Shankar-Hari, Steven Y C Tong, Alexis F Turgeon, Anne M Turner, Frank Leo Van De Veerdonk, Ryan Zarychanski, Cameron Green, Scott Berry, John C Marshall, Colin Mcarthur, Derek C Angus, Steven A Webb, Farah Al-Beidh, Derek C Angus, Djillali Annane, Yaseen M Arabi, Abi Beane, Wilma Van Bentum-Puijk, Scott Berry, Zahra Bhimani, Marc J M Bonten, Charlotte A Bradbury, Frank M Brunkhorst, Meredith Buxton, Allen Cheng, Lennie P G Derde, Lise J Estcourt, Herman Goossens, Anthony C Gordon, Cameron Green, Rashan Haniffa, Francois Lamontagne, Patrick R Lawler, Edward Litton, John C Marshall, Colin Mcarthur, Daniel F Mcauley, Shay Mcguinness, Bryan J Mcverry, Stephanie K Montgomery, Paul R Mouncey, Srinivas Murthy, Alistair D Nichol, Rachael Parke, Jane C Parker, Kathryn M Rowan, Marlene S Santos, Christopher W Seymour, Alexis F Turgeon, Anne M Turner, Frank Leo Van De Veerdonk, Steve Webb, Ryan Zarychanski, Yaseen M Arabi, Lewis Campbell, Allen Cheng, Lennie P G Derde, Andrew Forbes, David Gattas, Cameron Green, Stephane Heritier, Peter Kruger, Edward Litton, Colin Mcarthur, Shay Mcguinness, Alistair D Nichol, Rachael Parke, Jane C Parker, Sandra Peake, Jeffrey Presneill, Ian Seppelt, Tony Trapani, Anne M Turner, Steve Webb, Paul Young, Zahra Bhimani, Brian Cuthbertson, Rob Fowler, Francois Lamontagne, John C Marshall, Venika Manoharan, Srinivas Murthy, Marlene S Santos, Alexis F Turgeon, Ryan Zarychanski, Diptesh Aryal, Abi Beane, Arjen M Dondrop, Cameron Green, Rashan Haniffa, Madiha Hashmi, Issrah Jawad, Deva Jayakumar, John C Marshall, Colin Mcarthur, Srinivas Murthy, Timo Tolppa, Vanessa Singh, Steve Webb, Farah Al-Beidh, Derek C Angus, Djillali Annane, Wilma Van Bentum-Puijk, Scott Berry, Marc J M Bonten, Frank M Brunkhorst, Maurizio Cecconi, Lennie P G Derde, Stephan Ehrmann, Herman Goossens, Anthony C Gordon, Colin Mcarthur, Paul R Mouncey, Alistair D Nichol, Lorraine Parker, Mathias Pletz, Pedro Póvoa, Gernot Rohde, Kathryn M Rowan, Steve Webb, Brian Alexander, Derek C Angus, Kim Basile, Meredith Buxton, Timothy D Girard, Christopher M Horvat, David T Huang, Kelsey Linstrum, Florian Mayr, Bryan J Mcverry, Stephanie K Montgomery, Christopher W Seymour, Richard Beasley, Marc J M Bonten, Allen Cheng, Nick Daneman, Lennie P G Derde, Robert Fowler, David Gattas, Anthony C Gordon, Cameron Green, Peter Kruger, Colin Mcarthur, Steve Mcgloughlin, Susan C Morpeth, Srinivas Murthy, Alistair D Nichol, Mathias Pletz, David Paterson, Gernot Rohde, Steve Webb, Derek C Angus, Wilma Van Bentum-Puijk, Lennie P G Derde, Anthony C Gordon, Peter Kruger, Edward Litton, John C Marshall, Colin Mcarthur, Srinivas Murthy, Alistair D Nichol, Bala Venkatesh, Steve Webb, Derek C Angus, Scott Berry, Marc J M Bonten, Allen Cheng, Lennie P G Derde, Herman Goossens, Menno De Jong, John C Marshall, Colin Mcarthur, Srinivas Murthy, Tim Uyeki, Steve Webb, Derek C Angus, Yaseen M Arabi, Kenneth Baillie, Richard Beasley, Scott Berry, Marc J M Bonten, Allen Cheng, Menno De Jong, Lennie P G Derde, Eamon J Duffy, Rob Fowler, Herman Goossens, Anthony C Gordon, Cameron Green, Thomas E Hills, Colin Mcarthur, Susan C Morpeth, Srinivas Murthy, Alistair D Nichol, Katrina Orr
Intensive Care Medicine, doi:10.1007/s00134-021-06448-5
Purpose: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 . Methods: Critically 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. Results: We 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,
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1007/ s00134-021-06448-5. Author contributions For conceptualization: YMA, ACG, LPGD, ADN, SM, FAB, DA, LAS, AB, RB, ZB, MJMB, CAB, FMB, MB, AC, ADJ, EJD, LJE, RF, TDG, HG, RH, TEH, CMH, DTH, AJK, FL, PRL, KL, E Litton, DFM, AM, SMC, BJM, SKM, SCM, PRM, KO, RP, JCP, AEP, KMR, MSS, SWS, MSH, SYCT, AFT, AMT, FVV, RZ, CG, SB, JCM, CM, DA, SAW. Data curation: AB, AMH, CMH, KL, SSM, PRM, JCP, AMT, CG, CM. Formal analysis: LRB, MAD, MF, RJL, E Lorenzi, AM, CTS, SB, DA, SAW. Funding acquisition: ACG, LPGD, ADN, SM, MJMB, MB, KMR, JCM, CM, DA, SAW. Ethics approval The trial was approved by the relevant ethics committees in all regions. Consent to participate Written or verbal informed consent, in accordance with regional legislation, was obtained from all patients or from their surrogates. Consent for publication All authors approved the manuscript for submission. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Alexandra, Portsmouth ; David Pogson, Msc, Rose, Bsc et al., None
Ali Umrani, Siddiq; Mohiuddin, Shaikh, None
András, Hospital, Nyíregyháza ; Gábor, Szigligeti, Leszkoven et al., Auckland City Hospital, Cardiothoracic and Vascular ICU
Angus, Berry, Lewis, Al-Beidh, Arabi et al., The REMAP-CAP (randomized embedded multifactorial adaptive platform for community-acquired pneumonia) study. rationale and design, Ann Am Thorac Soc
Angus, Derde, Al-Beidh, Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19: the REMAP-CAP COVID-19 corticosteroid domain randomized clinical trial, Jama
Arabi, Asiri, Assiri, Balkhy, Bshabshe et al., Interferon beta-1b and lopinavir-ritonavir for middle east respiratory syndrome, N Engl J Med
Arabi, Fowler, Hayden, Critical care management of adults with community-acquired severe respiratory viral infection, Intensive Care Med
Arshad, Pertinez, Box, Tatham, Rajoli et al., Prioritization of Anti-SARS-Cov-2 drug repurposing opportunities based on plasma and target site concentrations derived from their established human pharmacokinetics, Clin Pharmacol Ther
Axfors, Schmitt, Janiaud, Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials, Nat Commun
Bay, Health Board ; Suresh, Pillai, Harford, Ivatt et al., Watford General Hospital
Best, Capparelli, Diep, Rossi, Farrell et al., Pharmacokinetics of lopinavir/ritonavir crushed versus whole tablets in children, J Acquir Immune Defic Syndr
Bhattarai, None
Bouadma, Lescure, Lucet, Yazdanpanah, Timsit, Severe SARS-CoV-2 infections: practical considerations and management strategy for intensivists, Intensive Care Med
Brompton, Patel, Dempster, Gummadi, Dormand et al., The Royal Free Hospital
Chan, Yao, Yeung, Deng, Bao et al., Treatment with lopinavir/ritonavir or interferon-beta1b improves outcome of MERS-CoV infection in a nonhuman primate model of common marmoset, J Infect Dis
Charles, Hospital, Schweikert, Wibrow, Anstey et al., John of God Midland Public and Private Hospitals
Choy, Wong, Kaewpreedee, Sia, Chen et al., Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro, Antiviral Res
Chu, Cheng, Hung, Wong, Chan et al., Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings, Thorax
Clwyd, Pugh, Menzies, Lean, Mbchb et al., None
Cmh, Lorenzi, Ssm, Skm, Jcp et al., Writing-review & editing: YMA
Cortes, Garcia-Salido, Pascual, Barrio, De et al., Patients SSGoS-C-iCIP (2020) A multicenter national survey of children with SARS-CoV-2 infection admitted to Spanish Pediatric Intensive Care Units, Intensive Care Med
Dagens, Sigfrid, Cai, Lipworth, Cheng et al., Scope, quality, and inclusivity of clinical guidelines produced early in the covid-19 pandemic: rapid review, BMJ
De Wilde, Jochmans, Posthuma, Zevenhoven-Dobbe, Van Nieuwkoop et al., Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture, Antimicrob Agents Chemother
Dodd, Freidlin, Korn, Platform trials-beware the noncomparable control group, N Engl J Med
Drayss, Md, Goebeler, Flor, Fragner et al., Almási Balogh
Ebenezer, Krishnamurthy, Lakshmi Ranganathan Phd, Manisha, Md et al., Nepal Grande International Hospital : Sushil Khanal, BSc
Edelstein, Venkatachalam, Dong, Autophagy inhibition by chloroquine and hydroxychloroquine could adversely affect acute kidney injury and other organ injury in critically ill patients with COVID-19, Kidney Int
Elizabeth, Hospital, Glasgow, Malcolm, Sim et al., None
Forest, Trust, Ratnam, Gill, Kirk et al., South Tyneside District Hospital: Christian Frey
General Hospital, Hollos, Coburn, Pgcert, Williams et al., Dhinesh Sundaran
Great, Hospitals, Trust, Watters, Mbbch et al., James Cook University Hospital: Jeremy Henning
Hamburg ; Stefan Kluge, Nierhaus, Md, Jarczak, Md et al., None
Health, Shehabi, Phd, Al-Bassam, Mbchb et al., None
Health, Trust, Touma, Holland, Hodge et al., None
Hey, Children's NHS Foundation Trust, BSc
Horie, Mcnicholas, Rezoagli, Pham, Curley et al., Emerging pharmacological therapies for ARDS: COVID-19 and beyond, Intensive Care Med
Hospital ; Pauline Austin, Mbchb, Chapman, Mbchb, Cabrelli et al., MSc; Pilgrim Hospital Boston
Hospital, French, Bates, Rn Gdipcritcare, Towns et al., Launceston General Hospital: Matthew Brain
Hospital, Gwenhael Colin, Zinzoni, Maquigneau, Henri-Lagarrigue et al., University Hospital of Leipzig
Hospital, Henrik Reschreiter, FFICM, Julie Camsooksai
Hospital, Kelsall, Mbchb, Cowley, Wild et al., None, BSc
Hospital, Knott, Hons, Mclined, Fracp et al., App.Sc.(Ag), Megan Ford, BSc
Hospital, Mcarthur, Hills, Dphil, Newby et al., None
Hospital, Peter, Alexander, Felton, Ferguson et al., York Teaching Hospital
Hospital, Thomas, Worner, Faulkner, Gendall et al., s Hospital
Hospital, Vasanth Mariappa, Smith, Pgcert, University et al., McGill University Health Centre
Hospital, Victoria Infirmary, Robinson, Msc, Patel et al., Newcastle upon Tyne
Hospital, Williams, Bmedsc, Kazemi, Bmedsc et al., None, PGCert
Hospital, Yusuff, Isgro, Brightling, Phd et al., None, BSc
Hospitalier, Veil, Beauvais: David, Luis, Mercier et al., Shidasp Siami
Investigators, Gordon, Mouncey, Interleukin-6 receptor antagonists in critically ill patients with covid-19, N Engl J Med
John, He, Bayesian analysis: a practical approach to interpret clinical trials and create clinical practice guidelines, Circ Cardiovasc Qual Outcomes
Kent Hospitals, Turki, Mbbch, Elsefi, Mrcp et al., Queen Elizabeth the Queen Mother Hospital
King's College, Hopkins, Smith, Noble, Theresa Depante et al., Lancashire Teaching Hospitals NHS Foundation Trust: Shondipon Laha
Kruger, Phd, Walsham, Mr, Meyer et al., The Prince Charles Hospital
Laterre, Berry, Blemings, Carlsen, Francois et al., Effect of selepressin vs placebo on ventilatorand vasopressor-free days in patients with septic shock: the SEPSIS-ACT randomized clinical trial, JAMA
Lazaro, Newman, None, MSc
Manchester, Infirmary, Felton, Bannard-Smith, Henry et al., Milton Keynes University Hospital
Marzolini, Stader, Stoeckle, Franzeck, Egli et al., Effect of systemic inflammatory response to SARS-CoV-2 on lopinavir and hydroxychloroquine plasma concentrations, Antimicrob Agents Chemother
Mcclintock, Msc, Warnock, Mpharm, Campbell Bsc et al., The Christie NHS Foundation Trust: Vidya Kasipandian
Mcintyre, Wilcox, Del Sorbo, Abdelhady, Romagnuolo et al., University Health Network
Memorial, Limb, Cowton, Bsc, Hons et al., Derriford Hospital
Mid, Essex Nhs Foundation Trust ; Aneta, Oborska, Maeda, Mbbs et al., None
Mineall, Mn; Lyell, Hospital, Fischer, Biradar et al., Logan Hospital, PGCert
Montgomery, Mouncey, Murthy, Nichol, Parke et al., MORU. Domain-Specific Working Groups: Antibiotic and Macrolide Duration Domain-Specific Working Group
Painvin, Guillot, Verdier, Gacouin, Maamar, Hydroxychloroquine pharmacokinetic in COVID-19 critically ill patients: an observational cohort study, Intensive Care Med
Pan, Peto, Henao-Restrepo, Repurposed antiviral drugs for covid-19-Interim WHO Solidarity Trial Results, N Engl J Med
Panjwani, Md, None
Park, Yu, Kim, Kim, Kim et al., Antiviral efficacies of FDA-approved drugs against SARS-CoV-2 infection in ferrets, mBio
Pastick, Okafor, Wang, Lofgren, Skipper et al., Review: hydroxychloroquine and chloroquine for treatment of SARS-CoV-2 (COVID-19), Open Forum Infect Dis
Perner, Vijayaraghavan, Venkatesh, How likely are COVID-19 interventions to benefit the sickest patients?, Intensive Care Med
Poincaré Hospital: Djillali Annane, Moine, Heming, Md, Maxime et al., None
Pourcine, Monchi, None
Queen's Hospital, Katary, Bell, Bsc, Wilcox et al., DREEAM Research Team; The Rotherham NHS Foundation Trust: Anil Hormis
Queen, Hospital, Birmingham: Dhruv, Parekh, Phd et al., None
Quintana, Viele, Lewis, Bayesian analysis: using prior information to interpret the results of clinical trials, JAMA
Recovery Collaborative Group, Horby, Mafham, Linsell, Bell et al., Effect of hydroxychloroquine in hospitalized patients with covid-19, N Engl J Med
Repatriation, Hospital, Cheung, Mbchb, Kol et al., None, BSc
Royal Infirmary ; Kathryn Puxty, Cathcart, Bsc, Mc Govern, Mbchb et al., None, BSc
Royal, Hospital, Rooney, Mbchb, Rodden et al., Royal Bournemouth and Christchurch Hospitals
Royal, Roy, Mbchb, Rostron, Phd et al., None, BSc
Salahuddin, Md, Masood, Croatia, General et al., University Hospital of Infectious Diseases
Sandwell, Birmingham, Trust, Hulme, Kannan et al., None
Shore, Everitt, Russell, Hons, Hacking et al., Clinical Hospital of Infectious and Tropical Diseases Bucharest
Siemieniuk, Bartoszko, Ge, Drug treatments for covid-19: living systematic review and network meta-analysis, BMJ
St, Mary's Hospital ; Anthony Gordon, Banach, Bsc, Fernández De Pinedo Artaraz et al., Stepping Hill Hospital
St, Vincent ; Critcare, Homes, Pgcert(critcare, Smith et al., 's Hospital (VIC)
Staff, Correction: COVID-19 prevention and treatment: a critical analysis of chloroquine and hydroxychloroquine clinical pharmacology, PLoS Med
Tenon, Muriel Fartoukh, Courtin, Labbe, Voiriot et al., None
Tu, Cao, Yu, Hu, Liu, Clinicolaboratory study of 25 fatal cases of COVID-19 in Wuhan, Intensive Care Med
University, Szakmany, Phd, Cherian, Bsc et al., None, MSc
Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res
Wang, Zhang, Yu, Tao, Xie, 15-day mortality and associated risk factors for hospitalized patients with COVID-19 in Wuhan, China: an ambispective observational cohort study, Intensive Care Med
Western, Hospital, Edinburgh, Rhodes, Phd et al., Wirral University Teaching Hospital NHSFT: Craig Denmade
Williams, Addip, Birch, Ba, Wiseman et al., Dorset County Hospital: Mark Pulletz
Worcester, Hospital ; Stephen Digby, Cowley, Wild, Bsc et al., Hospitals NHS Foundation Trust
Yao, Ye, Zhang, Cui, Huang et al., In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clin Infect Dis
Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop