Covid-19 Living Data

Trial ChiCTR2000030058
Publication Wang M, Clin Infect Dis, 2020 (published paper)
Dates: 2020-03-10 to 2020-04-12
Funding: Public/non profit (National Key Research and Development Plan for the Emergency Management of Novel Coronavirus Pneumonia, China; Wuhan Municipal Key Technology Project on Novel Coronavirus Pneumonia, China )
Conflict of interest: No

Methods
	RCT Blinding: Unblinded
	Location : Single center / China Follow-up duration (days): 77
Inclusion criteria	(1) aged 18-70 years with a diagnosis of COVID-19 conforming to the Chinese Guidelines; (2) hospitalized for prolonged post-symptomatic viral shedding; (3) able to orally take medication; (4) non-pregnant women; (5) effective contraception for 7 days after taking the last medication.
Exclusion criteria	(1) presence of any condition that would not allow the protocol to be followed, including known allergy to leflunomide, use of medications that are contraindicated with leflunomide and that could not be replaced or stopped during the trial period; (2) pregnant or breast-feeding; (3) known other serious comorbidities, such as liver, cardiovascular, cerebrovascular diseases, severe renal insufficiency or advanced cancer; (5) had received interferon before enrollment; (6) unwilling to participate in the study.
Interventions
	Treatment Leflunomide + Interferon alpha 2a Leflunomide: 50 mg orally every 12 hours 3 consecutive times, followed by 20 mg once a day for 8 days. (Total course of 10 days) Interferon alpha2a: 3 MIU nebulized twice a day for 10 days
	Control Interferon alpha 2a (3 million IU) Duration : 10 days
Participants
	Randomized 50 participants (n₁=26 / n₂= 24)
	Characteristics of participants N=50 Mean age : NR 22 males Severity : Mild: n=50 / Moderate: n=0/ Severe: n=0 Critical: n=0
Primary outcome
	In the register The days from positive to negative for viral nucleic acid testing
	In the report Duration of viral shedding (time from randomization to the first negative nucleic acid test of five consecutive RT-PCR results)
Documents available	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 of the article, the study registry was used in data extraction and risk of bias assessment. The study changed between registration and conduct from a multi-center, randomized, double-blind, controlled clinical trial to an open-label trial in a single center with a small sample of only convalescing patients with prolonged post-symptomatic viral shedding, due to the reduction in new COVID-19 patients in Wuhan, China after early March 2020. However, the authors have been transparent about this change. Outcomes reported are as per registration apart from duration of fever and pulmonary imaging remission as both these had resolved in all patients at time of enrollment. There is no change from the trial registration in the intervention and control treatments.