Trial NCT04276688
Publication Hung IF-N, Lancet, 2020 (published paper)
Dates: 10feb2020 to 20mar2020
Funding: Public/non profit (The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine)
Conflict of interest: No

Methods
RCT
Blinding: Unblinded
Location : Multicenter / Hong Kong
Follow-up duration (days): 30
Inclusion criteria
1. Recruited subjects include all adult patients ≥18 years hospitalised for virologically confirmed SARS-CoV-2 infection.
2. NEWS ≥1 upon recruitment
3. Auditory temperature ≥38°C or other symptoms including cough, sputum production, sore-throat, nasal discharge, myalgia, headache, fatigue or diarrhoea upon admission
4. Symptom duration ≤14 days
5. All subjects give written informed consent. For patients who are critically ill, requiring ICU, ventilation or confused, informed consent will be obtained from spouse, next-of-kin or legal guardians.
6. Subjects must be available to complete the study and comply with study procedures. Willingness to allow for serum samples to be stored beyond the study period, for potential additional future testing to better characterize immune response.
Exclusion criteria
1. Inability to comprehend and to follow all required study procedures.
2. Allergy or severe reactions to the study drugs
3. Patients with known prolonged QTc syndrome, ventricular cardiac arrhythmias, including torsade de pointes, second or third degree heart block, QTc interval ≥480ms
4. Patients taking medication that will potentially interact with lopinavir/ritonavir, ribavirin or interferon b-1b
5. Patients with known history of severe depression
6. Pregnant or lactating women
7. Received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to recruitment in this study or expect to receive an experimental agent during this study.
8. To participate in an unrelated trial during the current clinical trial. Nevertheless, the patients have the right to withdraw from the current clinical trial to join another clinical trial.
9. Have a history of alcohol or drug abuse in the last 5 years.
10. Have any condition that the investigator believes may interfere with successful completion of the study.
Interventions
Treatment
LPV/r+RBV+IFN beta1
Lopinavir/ritonavir: 400 mg/100 mg orally twice a day. Ribavirin: 400 mg twice a day. IFN beta-1b: 8 MIU subcutaneously, 3 doses maximum (Not given to patients recruited and treated between days 7 and 14). Treatments are given on alternate days for 14 days
Control
Lopinavir-Ritonavir (400mg/100mg)
Duration : 14 days
Participants
Randomized
127 participants (n1=86 / n2= 41)
Characteristics of participants
N=127
Mean age : 49
68 males
Severity : Mild: n=125 / Moderate: n=2/ Severe: n=0 Critical: n=0
Primary outcome
In the register
Time to negative nasopharyngeal swab (NPS) 2*19-n-CoV coronavirus viral RT-PCR
In the report
Time to achieve a negative RT-PCR result for SARS-CoV-2 in a nasopharyngeal swab sample.
Documents
avalaible

Protocol

Yes. In English

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 all available versions of the published/pre-print article, the study registry and the protocol were used in data extraction and risk of bias assessment. Some outcomes (e.g., clinical improvement defined as SOFA of 0) are reported in the paper, but not pre-specified in the trial registry/protocol. Treatment with interferon beta-1b depended on the time from symptom onset: participants recruited and treated between days 7 and 14 from symptom onset did not receive interferon beta-1b, whereas participants recruited and treated up to day 7 received interferion beta-1b. Randomization was not stratified. The sample size calculation seems to be based on mortality, which is not the primary outcome of the study. The authors do not explain their decision to use Mann Whitney U test to compare continuous variables, whereas Kruskal-Wallis H test was initially planned according to the protocol. The authors provided additional information about the study upon request on 22 July 2020.