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 |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe 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.MethodsThis 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.ResultsAs 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).ConclusionThe 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.).

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