Treating COVID-19 With Hydroxychloroquine (TEACH): A Multicenter, Double-Blind Randomized Controlled Trial in Hospitalized Patients

Abstract

Background Effective therapies to combat COVID-19 are urgently needed. Hydroxychloroquine (HCQ) has in vitro antiviral activity against SARS-CoV-2, but the clinical benefit of HCQ in treating COVID-19 is unclear. Randomized controlled trials are needed to determine the safety and efficacy of HCQ for the treatment of hospitalized patients with COVID-19. Methods We conducted a multicenter, double-blind, randomized clinical trial of HCQ among patients hospitalized with laboratory confirmed COVID-19. Subjects were randomized in a 1:1 ratio to HCQ or placebo for five days and followed for 30 days. The primary efficacy outcome was a severe disease progression composite endpoint (death, ICU admission, mechanical ventilation, ECMO, and/or vasopressor use) at day 14. Results A total of 128 patients were included in the intention-to-treat analysis. Baseline demographic, clinical, and laboratory characteristics were similar between HCQ (N=67) and placebo (N=61) arms. At day 14, 11 (16.4%) subjects assigned to HCQ and 6 (9.8%) subjects assigned to placebo met the severe disease progression endpoint, but this did not achieve statistical significance (P=.350). There were no significant differences in COVID-19 clinical scores, number of oxygen-free days, SARS-CoV-2 clearance, or adverse events between HCQ and placebo. HCQ was associated with a slight increase in mean corrected QT interval, an increased D-dimer, and a trend towards an increased length of stay. Conclusions In hospitalized patients with COVID-19, our data suggest that HCQ does not prevent severe outcomes or improve clinical scores. However, our conclusions are limited by a relatively small sample size, and larger randomized controlled trials or pooled analyses are needed.

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19: an international collaborative meta-analysis of randomized trials

“…We included 28 trials (14 unpublished trials, eight publications, and six preprints; of these, one publication and two preprints were identified for the first time in our search update). 13,[23][24][25][26][27][28][29][30][31][32][33][34][35] Individual trial characteristics are presented in Table 1 (28 included trials) and Supplement Table S1 (35 potentially eligible but unavailable). Overall, trial characteristics were not different between included and unavailable trials ( Table 2).…”

Interventions for treatment of COVID-19: second edition of a living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)

“…The identified trials compared the following interventions: 10 trials compared corticosteroids versus standard care [52,56,87,89,96–99] or placebo [68, 88]; four trials compared remdesivir versus standard care [86, 110] or placebo [43, 65]; 13 trials compared hydroxychloroquine versus standard care [34,35,42,48,54,55,58,59,105,110], or placebo [53, 108]; five trials compared lopinavir-ritonavir versus standard care [32,40,106,110] or a co-intervention alone [45]; two trials compared interferon beta-1a versus standard care [36, 110]; four trials compared convalescent plasma versus standard care [39,51,78,91]; three trials compared azithromycin versus standard care [83] or co-interventions with standard care [54] or without standard care [82]; three trials compared colchicine versus standard care [49], placebo plus standard care [92], or placebo plus a co-intervention [107]; two trials compared immunoglobulin versus standard care [57] or placebo [95]; six trials compared tocilizumab versus standard care [93,111–113], placebo with standard care [90] or favipiravir alone as co-intervention [114];two trials compared bromhexine versus standard care [94, 104]; and three trials compared favipiravir versus standard care [41, 67] or a co-intervention alone [114].…”

Immunomodulatory therapies for SARS-CoV-2 infection: a systematic literature review to inform EULAR points to consider

“…Of the nine RCTs on hydroxychloroquine (HCQ) in severe COVID-19, three studies at high RoB did not report any information regarding the proportions of patients requiring oxygen therapy/ NIMV/IMV, [13][14][15] two studies reported NIMV/IMV as exclusion criterion 16 17 and four studies detailed the proportion of enrolled patients received either oxygen therapy, NIMV or IMV. [18][19][20][21] The studies assessing mortality, 13 16 18-20 three at unclear and one at high RoB, agreed that the addition of HCQ to SOC did not provide any beneficial effect. As far as clinical severity is concerned, HCQ did not reduce the need of IMV, 13 16 19 but one RCT at unclear RoB demonstrated a higher risk of progression to IMV in patients treated with HCQ+SOC compared with SOC only 18 (tables 1 and 2).…”