Leflunomide + Interferon alpha2a vs Interferon alpha2a (RCT)

Hospitalized patients

FOREST PLOTS -2021-06-18

Studies description

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
LEF+IFN alpha2a
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 alpha 2a: 3 MIU nebulized twice a day for 10 days
Control
Interferon alpha-2a
3 MIU nebulized twice a day for 10 days

Participants
Randomized
participants :
Interferon alpha-2a=24
LEF+IFN alpha2a=26
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
avalaible

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

Not reported
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.