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Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial.
JAMA. 2020 Sep 15; 324(11):1048-1057.JAMA

Abstract

IMPORTANCE

Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown.

OBJECTIVE

To determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment.

DESIGN, SETTING, AND PARTICIPANTS

Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020.

INTERVENTIONS

Patients were randomized in a 1:1:1 ratio to receive a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d.

MAIN OUTCOMES AND MEASURES

The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group.

RESULTS

Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 [interquartile range, 46-66] years; 227 [39%] women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care.

CONCLUSIONS AND RELEVANCE

Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT04292730.

Links

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Authors+Show Affiliations

Spinner CD
Technical University of Munich, School of Medicine, University Hospital Rechts der Isar, Munich, Germany.
Gottlieb RL
Baylor University Medical Center, Dallas, Texas.
Criner GJ
Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.
Arribas López JR
Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain.
Cattelan AM
Azienda Ospedaliera di Padova, Padova, Italy.
Soriano Viladomiu A
Hospital Clinic of Barcelona, IDIBAPS, Barcelona, Spain.
Ogbuagu O
Yale School of Medicine, New Haven, Connecticut.
Malhotra P
North Shore University Hospital, Manhasset, New York.
Mullane KM
University of Chicago, Chicago, Illinois.
Castagna A
IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy.
Chai LYA
National University Health System, Singapore.
Roestenberg M
Leiden University Medical Center, Leiden, the Netherlands.
Tsang OTY
Princess Margaret Hospital, Hong Kong, China.
Bernasconi E
Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
Le Turnier P
University of Nantes, Nantes, France.
Chang SC
National Taiwan University Hospital, Taipei, Taiwan.
SenGupta D
Gilead Sciences, Foster City, California.
Hyland RH
Gilead Sciences, Foster City, California.
Osinusi AO
Gilead Sciences, Foster City, California.
Cao H
Gilead Sciences, Foster City, California.
Blair C
Gilead Sciences, Foster City, California.
Wang H
Gilead Sciences, Foster City, California.
Gaggar A
Gilead Sciences, Foster City, California.
Brainard DM
Gilead Sciences, Foster City, California.
McPhail MJ
King's College, London, England.
Bhagani S
Royal Free Hospital, London, England.
Ahn MY
Seoul Medical Center, Seoul, South Korea.
Sanyal AJ
Virginia Commonwealth University, Richmond.
Huhn G
Cook County Health, Chicago, Illinois.
Marty FM
Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
GS-US-540-5774 Investigators
No affiliation info available

MeSH

Adenosine MonophosphateAdministration, IntravenousAgedAlanineAntiviral AgentsBetacoronavirusCOVID-19Coronavirus InfectionsDrug Administration ScheduleFemaleHospitalizationHumansMaleMiddle AgedOdds RatioPandemicsPatient AcuityPneumonia, ViralSARS-CoV-2Treatment OutcomeCOVID-19 Drug Treatment

Pub Type(s)

Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32821939

Clinical Trial Links

Clinical trial which this article describes
Baricitinib in Hospitalized Covid-19 Patients With Diabetes Mellitus

Citation

Spinner, Christoph D., et al. "Effect of Remdesivir Vs Standard Care On Clinical Status at 11 Days in Patients With Moderate COVID-19: a Randomized Clinical Trial." JAMA, vol. 324, no. 11, 2020, pp. 1048-1057.
Spinner CD, Gottlieb RL, Criner GJ, et al. Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2020;324(11):1048-1057.
Spinner, C. D., Gottlieb, R. L., Criner, G. J., Arribas López, J. R., Cattelan, A. M., Soriano Viladomiu, A., Ogbuagu, O., Malhotra, P., Mullane, K. M., Castagna, A., Chai, L. Y. A., Roestenberg, M., Tsang, O. T. Y., Bernasconi, E., Le Turnier, P., Chang, S. C., SenGupta, D., Hyland, R. H., Osinusi, A. O., ... Marty, F. M. (2020). Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial. JAMA, 324(11), 1048-1057. https://doi.org/10.1001/jama.2020.16349
Spinner CD, et al. Effect of Remdesivir Vs Standard Care On Clinical Status at 11 Days in Patients With Moderate COVID-19: a Randomized Clinical Trial. JAMA. 2020 Sep 15;324(11):1048-1057. PubMed PMID: 32821939.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial. AU - Spinner,Christoph D, AU - Gottlieb,Robert L, AU - Criner,Gerard J, AU - Arribas López,José Ramón, AU - Cattelan,Anna Maria, AU - Soriano Viladomiu,Alex, AU - Ogbuagu,Onyema, AU - Malhotra,Prashant, AU - Mullane,Kathleen M, AU - Castagna,Antonella, AU - Chai,Louis Yi Ann, AU - Roestenberg,Meta, AU - Tsang,Owen Tak Yin, AU - Bernasconi,Enos, AU - Le Turnier,Paul, AU - Chang,Shan-Chwen, AU - SenGupta,Devi, AU - Hyland,Robert H, AU - Osinusi,Anu O, AU - Cao,Huyen, AU - Blair,Christiana, AU - Wang,Hongyuan, AU - Gaggar,Anuj, AU - Brainard,Diana M, AU - McPhail,Mark J, AU - Bhagani,Sanjay, AU - Ahn,Mi Young, AU - Sanyal,Arun J, AU - Huhn,Gregory, AU - Marty,Francisco M, AU - ,, PY - 2020/8/22/pubmed PY - 2020/9/30/medline PY - 2020/8/22/entrez SP - 1048 EP - 1057 JF - JAMA JO - JAMA VL - 324 IS - 11 N2 - IMPORTANCE: Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown. OBJECTIVE: To determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020. INTERVENTIONS: Patients were randomized in a 1:1:1 ratio to receive a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d. MAIN OUTCOMES AND MEASURES: The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group. RESULTS: Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 [interquartile range, 46-66] years; 227 [39%] women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care. CONCLUSIONS AND RELEVANCE: Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04292730. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/32821939/Effect_of_Remdesivir_vs_Standard_Care_on_Clinical_Status_at_11_Days_in_Patients_With_Moderate_COVID_19:_A_Randomized_Clinical_Trial_ DB - PRIME DP - Unbound Medicine ER -