Trial NCT04369742
Publication Ulrich RJ, Open Forum Infect Di, 2020 (published paper)
Dates: 2020-04-17 to 2020-05-12
Funding: Public/non profit (NYU Grossman School of Medicine; National Center for Advancing Translational Sciences, National Institutes of Health)
Conflict of interest: No
| Methods | |
| RCT Blinding: double blinding | |
| Location :
Multicenter / USA Follow-up duration (days): 30 | |
| Inclusion criteria | Hospitalized patients with positive SARS-CoV-2 RT-PCR...In addition to a positive RT-PCR within 72 hours of enrollment, at least one COVID-19 symptom (e.g., fever, cough, dyspnea, nausea, diarrhea, myalgia, anosmia, dysgeusia) and the subject’s (or legally authorized representative’s) written informed consent |
| Exclusion criteria | Admitted to the ICU, mechanical ventilation, extracorporeal membrane oxygenation, and/or vasopressor use at enrollment, had received any doses of hydroxychloroquine or chloroquine within 30 days, were unable to take oral medications, were allergic to HCQ or CQ, had a baseline corrected QT interval >500 milliseconds, were on concomitant therapy with antiarrhythmic medications (flecainide, amiodarone, digoxin, procainamide, propafenone, thioridazine, or pimozide), had a history of cardiac arrest, retinal disease, or glucose-6-phosophate dehydrogenase deficiency |
| Interventions | |
| Treatment
Hydroxychloroquine 400 mg (2 tablets) twice daily (day 1) and 200 mg (1 tablet) twice daily (days 2-5) |
|
| Control
Placebo (calcium citrate 200 mg) Duration : 5 days | |
| Participants | |
| Randomized 128 participants (n1=67 / n2= 61) | |
| Characteristics of participants N=128 Mean age : 66.2 76 males Severity : Mild: n=45 / Moderate: n=62/ Severe: n=21 Critical: n=0 | |
| Primary outcome | |
| In the register Cumulative incidence of SAEs through day 30; Cumulative incidence of grade 3 or 4 AEs through day 30; Incidence of discontinuation of therapy (for any reason); Severe disease progression composite outcome | |
| In the report Proportion of subjects meeting a severe COVID-19 progression composite endpoint (death, ICU admission, mechanical ventilation, ECMO, and/or vasopressor use) at day 14; Cumulative incidence of SAE, grade 3 or 4 AE, and/or discontinuation of therapy at day 30. | |
| Documents avalaible |
Protocol NR Statistical plan NR Data-sharing stated Yes |
| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Some concerns |
| General comment | In addition to the accepted manuscript, the study registry was used in data extraction and risk of bias assessment. The protocol and data analysis plan were not available. The report stated the existence of the protocol in the supplementary materials but this could be found. The report stated that the protocol was amended to allow for co-enrollment in other COVID-19 therapeutic trials and for the enrollment of children and pregnant women. The study was registered retrospectively. The authors states that the study team initiated registration prospectively, but a separate office submitted the registration later due to administrative delays during COVID-19. The study was terminated early by the investigators due to a decrease in COVID-19 admissions and consequently did not achieve the target sample size. There was no change from the trial registration in the intervention and control treatments. The primary outcomes indicated in registry reflected the primary outcomes reported in the paper. |