Trial NCT04381936
Publication Horby P, N Engl J Med, 2020 (published paper)
Dates: 25mar2020 to 05jun2020
Funding: Mixed (University of Oxford from UK Research and Innovation/National Institute for Health Research (NIHR); NIHR Oxford Biomedical Research Centre; Wellcome; Bill and Melinda Gates Foundation; Department for International Development; Health Data Research UK)
Conflict of interest: No
| Methods | |
| RCT Blinding: Unblinded | |
| Location :
Multicenter / UK Follow-up duration (days): 28 | |
| Inclusion criteria | Hospitalized patients were eligible for the study if they had clinically suspected or laboratory confirmed SARS-CoV-2 infection and no medical history that might, in the opinion of the attending clinician, put the patient at significant risk if they were to participate in the trial. Initially, recruitment was limited to patients aged at least 18 years but from 9 May 2020, the age limit was removed. |
| Exclusion criteria | Patients with known prolonged electrocardiograph QTc interval were ineligible for the hydroxychloroquine arm. Co-administration with medications that prolong the QT interval was not an absolute contraindication but attending clinicians were advised to check the QT interval by performing an electrocardiogram. |
| Interventions | |
| Treatment
Hydroxychloroquine 200 mg tablet orally: 4 tablets at baseline and at 6 hours, then 2 tablets starting at 12 hours after initial dose and then every 12 hours for the next 9 days |
|
| Control
Standard care Definition of Standard care: * | |
| Participants | |
| Randomized 4716 participants (n1=1561 / n2= 3155) | |
| Characteristics of participants N=4716 Mean age : 65.3 2934 males Severity : Mild: n=1112 / Moderate: n=*/ Severe: n=* Critical: n=793 | |
| Primary outcome | |
| In the register All-cause mortality [ Time Frame: Within 28 days after randomisation ] | |
| In the report 28-day mortality | |
| Documents available |
Protocol Yes. In English Statistical plan Yes 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 published article, the pre-print preliminary report and supplementary appendix, the study registry, protocol, and statistical analysis plan were also used in data extraction and risk of bias assessment. There is no change from the trial registration in the intervention and control treatments nor primary and secondary outcomes.
On 4 June, in response to a request from the MHRA, the independent Data Monitoring Committee conducted a review of the data and recommended the chief investigators review the unblinded data on the hydroxychloroquine arm of the trial. The Chief Investigators and Trial Steering Committee concluded that the data showed no beneficial effect of hydroxychloroquine in patients hospitalized with COVID-19. The decision to stop enrolment of participants to the hydroxychloroquine arm was made on June 5 and investigators were advised that any patients currently taking hydroxychloroquine as part of the study should discontinue the treatment. |