Trial ISRCTN83971151; NCT04315948
Publication SOLIDARITY (HCQ) - Pan H, N Engl J Med (2020) (published paper)
Dates: 2020-03-22 to 2020-10-04
Funding: Mixed (World Health Organization; Mylan (drug donation))
Conflict of interest: No

Methods
RCT
Blinding: Unblinded
Location : Multicenter / Multinational (30)
Follow-up duration (days): 28
Inclusion criteria
  • Age ≥18 years, hospitalized with a diagnosis of COVID-19, not known to have received any study drug, without anticipated transfer elsewhere within 72 hours, and, in the physician’s view, with no contra-indication to any study drug.
Exclusion criteria
  • The only exclusions were patients without clear consent to follow-up
Interventions
Treatment
Hydroxychloroquine
200 mg tablets orally: four tablets at hour 0, four tablets at hour 6, and, starting at hour 12, two tablets twice daily for 10 days
Control
Standard care

Participants
Randomized
participants :
Hydroxychloroquine=954
Standard care=909
Characteristics of participants
N= 1863
Mean age : NR
1109 males
Severity : Mild: n=686 / Moderate: n=* / Severe: n=* Critical: n=*
Number of vaccinated participants: NR
Primary outcome
In the register
All-cause mortality, subdivided by the severity of disease at the time of randomization, measured using patient records throughout the study
In the report
In-hospital mortality
Documents
available

Protocol

Yes. In English

Statistical plan

NR

Data-sharing willing stated in the publication:

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
Low
General comment In addition to all available versions of the published manuscript, the pre-print article, the study registry and protocol were used in data extraction and risk of bias assessment. This was a report of interim results of an adaptive trial evaluating 4 drugs: Remdesivir, Hydroxychloroquine, Lopinavir, and Interferon-β1a. No target sample size was pre-specified.
Quote: "The protocol stated “The larger the number entered the more accurate the results will be, but numbers entered will depend on how the epidemic develops… it may be possible to enter several thousand hospitalised patients with relatively mild disease and a few thousand with severe disease, but realistic, appropriate sample sizes could not be estimated at the start of the trial.” The Executive Group, blind to any findings, decided the timing of release of interim results."
Quote: "The hydroxychloroquine, lopinavir, and interferon regimens were discontinued for futility on, respectively, June 19, July 4, and October 16, 2020."
There was no change from the trial registration in the intervention and control treatments, nor in the primary and secondary outcomes.
Discrepancy between exclusion criteria in the protocol and in the paper. Lack of clarity on why/how Hydrochloroquine was administered to ventilated patients(for lopinavir, it is stated: Other formulations were not provided, so ventilated patients received no study Lopinavir while unable to swallow).
This study was updated on December 9th using data from the published manuscript.