Publication Tang W, BMJ, 2020 (published paper)
Dates: 11feb2020 to 29feb2020
Funding: Mixed (Emergent Projects of National Science and Technology; National Natural Science Foundation of China; National Key Research and Development Program of China; Shanghai Municipal Key Clinical Specialty; National Innovative Research Team of High-level Loc)
Conflict of interest: No
Multicenter / China |
Follow-up duration (days): 20
|Inclusion criteria||1) age >18 years; |
2) with ongoing SARS–CoV–2 infection confirmed in upper or lower respiratory tract specimens with real–time reverse–transcriptase–polymerase–chain–reaction (RT–PCR);
3) willingness to participate;
4) consent not to be enrolled by other clinical trials during the study period.
|Exclusion criteria||1) age <18 years; |
2) with severe conditions including malignancies, heart/liver/kidney disease or poorly controlled metabolic diseases;
3) not suitable to be administrated through the gastrointestinal tract;
4) pregnant or lactation;
5) allergy to HCQ;
6) unable to cooperate with investigators due to cognitive impairments or poor mental status;
7) with severe liver disease (e.g. Child Pugh grade C, alanine aminotransferase >5 fold of times upper limit);
8) with severe renal impairment (estimated glomerular filtration rate <30 mL/min/1.73 m2) or receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis. In the original protocol, patients with severe COVID–19 were excluded. Considering the anti–inflammatory property of HCQ might favor disease regression, we decided to include patients with severe COVID–19. (change approved by the Ethics Committee on February 17, 2020).
Hydroxychloroquine (1200mg for 3 days, then 800mg)
Co-Intervention: Standard care
Duration : 14 d mild. 21 d
Definition of Standard care: Standard care according to "the updating National clinical practice guidelines for COVID-19 in China"
150 participants (n1=75 / n2= 75)
|Characteristics of participants|
Mean age : 46.1
Severity : Mild: n=22 / Moderate: n=126/ Severe: n=2 Critical: n=0
|In the register|
|In the report|
The primary outcome for this trial was whether patients had a negative conversion of SARS–CoV–2 by 28 days and whether patients with severe COVID–19 had a clinical improvement by 28 days.
Yes. In English
|Risk of bias
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
|General comment||In addition to all available versions of the published/pre-print article, the study registry, protocol, and statistical analysis plan were used in data extraction and risk of bias assessment. The study was terminated early by the IDMC after interim review of safety and efficacy data. The study did not achieve the target sample size specified in the trial registry. The primary outcome included clinical improvement, however the authors do not report this. They provide an explanation for this change: "since the trial was stopped early and only 2 patients with severe disease were enrolled, results on clinical improvement are not presented". There is no change from the trial registration in the intervention and control treatments. Some outcomes (e.g., all cause mortality) are reported in the paper, but were not pre-specified in the trial registry. They are, however, pre-specified in the protocol. On July 15th 2020, we received additional information from authors on this study.|