Dataset Information

Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial.

ABSTRACT:

Importance

Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed.

Objective

To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19.

Design, setting, and participants

This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients.

Interventions

Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237).

Main outcomes and measures

The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality.

Results

Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, -0.2% [95% CI, -5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]).

Conclusions and relevance

Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults.

Trial registration

ClinicalTrials.gov: NCT04332991.

SUBMITTER: Self WH

PROVIDER: S-EPMC7653542 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial.

Self Wesley H WH Semler Matthew W MW Leither Lindsay M LM Casey Jonathan D JD Angus Derek C DC Brower Roy G RG Chang Steven Y SY Collins Sean P SP Eppensteiner John C JC Filbin Michael R MR Files D Clark DC Gibbs Kevin W KW Ginde Adit A AA Gong Michelle N MN Harrell Frank E FE Hayden Douglas L DL Hough Catherine L CL Johnson Nicholas J NJ Khan Akram A Lindsell Christopher J CJ Matthay Michael A MA Moss Marc M Park Pauline K PK Rice Todd W TW Robinson Bryce R H BRH Schoenfeld David A DA Shapiro Nathan I NI Steingrub Jay S JS Ulysse Christine A CA Weissman Alexandra A Yealy Donald M DM Thompson B Taylor BT Brown Samuel M SM Steingrub Jay J Smithline Howard H Tiru Bogdan B Tidswell Mark M Kozikowski Lori L Thornton-Thompson Sherell S De Souza Leslie L Hou Peter P Baron Rebecca R Massaro Anthony A Aisiku Imoigele I Fredenburgh Lauren L Seethala Raghu R Johnsky Lily L Riker Richard R Seder David D May Teresa T Baumann Michael M Eldridge Ashley A Lord Christine C Shapiro Nathan N Talmor Daniel D O’Mara Thomas T Kirk Charlotte C Harrison Kelly K Kurt Lisa L Schermerhorn Margaret M Banner-Goodspeed Valerie V Boyle Katherine K Dubosh Nicole N Filbin Michael M Hibbert Kathryn K Parry Blair B Lavin-Parsons Kendall K Pulido Natalie N Lilley Brendan B Lodenstein Carl C Margolin Justin J Brait Kelsey K Jones Alan A Galbraith James J Peacock Rebekah R Nandi Utsav U Wachs Taylor T Matthay Michael M Liu Kathleen K Kangelaris Kirsten K Wang Ralph R Calfee Carolyn C Yee Kimberly K Hendey Gregory G Chang Steven S Lim George G Qadir Nida N Tam Andrea A Beutler Rebecca R Levitt Joseph J Wilson Jenny J Rogers Angela A Vojnik Rosemary R Roque Jonasel J Albertson Timothy T Chenoweth James J Adams Jason J Pearson Skyler S Juarez Maya M Almasri Eyad E Fayed Mohamed M Hughes Alyssa A Hillard Shelly S Huebinger Ryan R Wang Henry H Vidales Elizabeth E Patel Bela B Ginde Adit A Moss Marc M Baduashvili Amiran A McKeehan Jeffrey J Finck Lani L Higgins Carrie C Howell Michelle M Douglas Ivor I Haukoos Jason J Hiller Terra T Lyle Carolynn C Cupelo Alicia A Caruso Emily E Camacho Claudia C Gravitz Stephanie S Finigan James J Griesmer Christine C Park Pauline P Hyzy Robert R Nelson Kristine K McDonough Kelli K Olbrich Norman N Williams Mark M Kapoor Raj R Nash Jean J Willig Meghan M Ford Henry H Gardner-Gray Jayna J Ramesh Mayur M Moses Montefiore M Ng Gong Michelle M Aboodi Michael M Asghar Ayesha A Amosu Omowunmi O Torres Madeline M Kaur Savneet S Chen Jen-Ting JT Hope Aluko A Lopez Brenda B Rosales Kathleen K Young You Jee J Mosier Jarrod J Hypes Cameron C Natt Bhupinder B Borg Bryan B Salvagio Campbell Elizabeth E Hite R Duncan RD Hudock Kristin K Cresie Autumn A Alhasan Faysal F Gomez-Arroyo Jose J Duggal Abhijit A Mehkri Omar O Hastings Andrei A Sahoo Debasis D Abi Fadel Francois F Gole Susan S Shaner Valerie V Wimer Allison A Meli Yvonne Y King Alexander A Terndrup Thomas T Exline Matthew M Pannu Sonal S Robart Emily E Karow Sarah S Hough Catherine C Robinson Bryce B Johnson Nicholas N Henning Daniel D Campo Monica M Gundel Stephanie S Seghal Sakshi S Katsandres Sarah S Dean Sarah S Khan Akram A Krol Olivia O Jouzestani Milad M Huynh Peter P Weissman Alexandra A Yealy Donald D Scholl Denise D Adams Peter P McVerry Bryan B Huang David D Angus Derek D Schooler Jordan J Moore Steven S Files Clark C Miller Chadwick C Gibbs Kevin K LaRose Mary M Flores Lori L Koehler Lauren L Morse Caryn C Sanders John J Langford Caitlyn C Nanney Kristen K MdalaGausi Masiku M Yeboah Phyllis P Morris Peter P Sturgill Jamie J Seif Sherif S Cassity Evan E Dhar Sanjay S de Wit Marjolein M Mason Jessica J Goodwin Andrew A Hall Greg G Grady Abbey A Chamberlain Amy A Brown Samuel S Bledsoe Joseph J Leither Lindsay L Peltan Ithan I Starr Nathan N Fergus Melissa M Aston Valerie V Montgomery Quinn Q Smith Rilee R Merrill Mardee M Brown Katie K Armbruster Brent B Harris Estelle E Middleton Elizabeth E Paine Robert R Johnson Stacy S Barrios Macy M Eppensteiner John J Limkakeng Alexander A McGowan Lauren L Porter Tedra T Bouffler Andrew A Leahy J. Clancy JC deBoisblanc Bennet B Lammi Matthew M Happel Kyle K Lauto Paula P Self Wesley W Casey Jonathan J Semler Matthew M Collins Sean S Harrell Frank F Lindsell Christopher C Rice Todd T Stubblefield William W Gray Christopher C Johnson Jakea J Roth Megan M Hays Margaret M Torr Donna D Zakaria Arwa A Schoenfeld David D Thompson Taylor T Hayden Douglas D Ringwood Nancy N Oldmixon Cathryn C Ulysse Christine C Morse Richard R Muzikansky Ariela A Fitzgerald Laura L Whitaker Samuel S Lagakos Adrian A Brower Roy R Reineck Lora L Aggarwal Neil N Bienstock Karen K Freemer Michelle M Maclawiw Myron M Weinmann Gail G Morrison Laurie L Gillespie Mark M Kryscio Richard R Brodie Daniel D Zareba Wojciech W Rompalo Anne A Boeckh Michael M Parsons Polly P Christie Jason J Hall Jesse J Horton Nicholas N Zoloth Laurie L Dickert Neal N Diercks Deborah D

JAMA 20201201 21

<h4>Importance</h4>Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed.<h4>Objective</h4>To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19.<h4>Design, setting, and participants</h4>This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 ...[more]

PMID: 33165621

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Project description:Background The initial insights from the studies on COVID-19 had been disappointing, indicating the necessity of an aggravated search for alternative strategies. In this regard, the adjunct potential of yoga has been proposed for enhancing the effectiveness of the standard of care with respect to COVID-19 management. We tested whether a telemodel of yoga intervention could aid in better clinical management for hospitalized patients with mild-to-moderate COVID-19 when complemented with the standard of care. Methods This was a randomized controlled trial conducted at the Narayana Hrudyalaya, Bengaluru, India, on hospitalized patients with mild-to-moderate COVID-19 infection enrolled between 31 May and 22 July 2021. The patients (n = 225) were randomized in a 1:1 ratio [adjunct tele-yoga (n = 113) or standard of care]. The adjunct yoga group received intervention in tele-mode within 4-h post-randomization until 14 days along with the standard of care. The primary outcome was the clinical status on day 14 post-randomization, assessed with a seven-category ordinal scale. The secondary outcome set included scores on the COVID Outcomes Scale on day 7, follow-up for clinical status and all-cause mortality on day 28, post-randomization, duration of days at the hospital, 5th-day changes post-randomization for viral load expressed as cyclic threshold (Ct), and inflammatory markers and perceived stress scores on day 14. Results As compared with the standard of care alone, the proportional odds of having a higher score on the 7-point ordinal scale on day 14 were ~1.8 for the adjunct tele-yoga group (OR = 1.83, 95% CI, 1.11–3.03). On day 5, there were significant reductions in CRP (P = 0.001) and LDH levels (P = 0.029) in the adjunct yoga group compared to the standard of care alone. CRP reduction was also observed as a potential mediator for the yoga-induced improvement of clinical outcomes. The Kaplan–Meier estimate of all-cause mortality on day 28 was the adjusted hazard ratio (HR) of 0.26 (95% CI, 0.05–1.30). Conclusion The observed 1.8-fold improvement in the clinical status on day 14 of patients of COVID-19 with adjunct use of tele-yoga contests its use as a complementary treatment in hospital settings.

Project description:BackgroundHydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (Covid-19) on the basis of in vitro activity and data from uncontrolled studies and small, randomized trials.MethodsIn this randomized, controlled, open-label platform trial comparing a range of possible treatments with usual care in patients hospitalized with Covid-19, we randomly assigned 1561 patients to receive hydroxychloroquine and 3155 to receive usual care. The primary outcome was 28-day mortality.ResultsThe enrollment of patients in the hydroxychloroquine group was closed on June 5, 2020, after an interim analysis determined that there was a lack of efficacy. Death within 28 days occurred in 421 patients (27.0%) in the hydroxychloroquine group and in 790 (25.0%) in the usual-care group (rate ratio, 1.09; 95% confidence interval [CI], 0.97 to 1.23; P = 0.15). Consistent results were seen in all prespecified subgroups of patients. The results suggest that patients in the hydroxychloroquine group were less likely to be discharged from the hospital alive within 28 days than those in the usual-care group (59.6% vs. 62.9%; rate ratio, 0.90; 95% CI, 0.83 to 0.98). Among the patients who were not undergoing mechanical ventilation at baseline, those in the hydroxychloroquine group had a higher frequency of invasive mechanical ventilation or death (30.7% vs. 26.9%; risk ratio, 1.14; 95% CI, 1.03 to 1.27). There was a small numerical excess of cardiac deaths (0.4 percentage points) but no difference in the incidence of new major cardiac arrhythmia among the patients who received hydroxychloroquine.ConclusionsAmong patients hospitalized with Covid-19, those who received hydroxychloroquine did not have a lower incidence of death at 28 days than those who received usual care. (Funded by UK Research and Innovation and National Institute for Health Research and others; RECOVERY ISRCTN number, ISRCTN50189673; ClinicalTrials.gov number, NCT04381936.).

Project description:ImportanceRemdesivir 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.ObjectiveTo 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 participantsRandomized, 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.InterventionsPatients 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 measuresThe 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.ResultsAmong 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 relevanceAmong 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 registrationClinicalTrials.gov Identifier: NCT04292730.

Project description:BackgroundHydroxychloroquine has been widely administered to patients with Covid-19 without robust evidence supporting its use.MethodsWe examined the association between hydroxychloroquine use and intubation or death at a large medical center in New York City. Data were obtained regarding consecutive patients hospitalized with Covid-19, excluding those who were intubated, died, or discharged within 24 hours after presentation to the emergency department (study baseline). The primary end point was a composite of intubation or death in a time-to-event analysis. We compared outcomes in patients who received hydroxychloroquine with those in patients who did not, using a multivariable Cox model with inverse probability weighting according to the propensity score.ResultsOf 1446 consecutive patients, 70 patients were intubated, died, or discharged within 24 hours after presentation and were excluded from the analysis. Of the remaining 1376 patients, during a median follow-up of 22.5 days, 811 (58.9%) received hydroxychloroquine (600 mg twice on day 1, then 400 mg daily for a median of 5 days); 45.8% of the patients were treated within 24 hours after presentation to the emergency department, and 85.9% within 48 hours. Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloroquine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs. 360). Overall, 346 patients (25.1%) had a primary end-point event (180 patients were intubated, of whom 66 subsequently died, and 166 died without intubation). In the main analysis, there was no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32). Results were similar in multiple sensitivity analyses.ConclusionsIn this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed. (Funded by the National Institutes of Health.).

Project description:ImportanceOveractivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.ObjectiveTo determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.Design, setting, and participantsIn an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).InterventionsPatients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.Main outcomes and measuresThe primary outcome was organ support-free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.ResultsOn February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support-free days among critically ill patients was 10 (-1 to 16) in the ACE inhibitor group (n = 231), 8 (-1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support-free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).Conclusions and relevanceIn this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.Trial registrationClinicalTrials.gov Identifier: NCT02735707.

Dataset Information

Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Conclusions and relevance

Trial registration

Publications

Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial.

Similar Datasets

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