Trial NCT04273763
Publication Li T, Clin Transl Sci , 2020 (published paper)
Funding: Public/non profit ( Special Project for Significant New Drug Research and Development in the Major National Science and Technology Projects of China )
Conflict of interest: No
| Methods | |
| RCT Blinding: Unblinded | |
| Location :
Single center / China Follow-up duration (days): 21 | |
| Inclusion criteria | Age ≥ 18 years but ≤ 80 years;
2) confirmed or clinically suspected mild or moderate coronavirus pneumonia (COVID-19) based on China’s Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Provisional 5th Edition); 3) signed informed consent. |
| Exclusion criteria | 1) alanine aminotransferase (ALT) ≥5× the upper limit of normal (ULN), total bilirubin level ≥3× ULN, or creatinine (Cr) ≥1.5× ULN;
2) severe liver disease; 3) severe or critical cases; 4) previous history of severe gastrointestinal diseases such as gastric ulcers or bleeding; 5) lactose intolerance; 6) allergic to BRH or ingredients including starch, lactose, and magnesium stearate; 7) pregnant or breastfeeding women. |
| Interventions | |
| Treatment
Bromhexine 32 mg orally 3 times a day for 14 days |
|
| Control
Standard care Definition of Standard care: Antiviral drugs, including arbidol hydrochloride granules (0.1g-0.2g tid) and recombinant human interferon α2b spray (0.083 ml tid), on the doctors’ discretion according to China’s Novel Coronavirus Pneumonia Diagnosis and Treatment Plan. | |
| Participants | |
| Randomized 18 participants (n1=12 / n2= 6) | |
| Characteristics of participants N=18 Mean age : NR 14 males Severity : Mild: n=* / Moderate: n=*/ Severe: n=0 Critical: n=0 | |
| Primary outcome | |
| In the register Time to clinical recovery after treatment and Rate of aggravation [Time Frame: within 14 days from the start of medication] | |
| In the report Clinical recovery and the deterioration rate after initiation of medications | |
| Documents avalaible |
Protocol NR Statistical plan NR Data-sharing stated No |
| 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 pre-print article, the study registry was used in data extraction and risk of bias assessment. This is a report of the pilot study of a randomized controlled trial.
Quote: "The number of patients finally included was less than expected due to the successful containment of disease in China." There were some differences from the trial registration in the secondary outcomes. The trial registry reported the intervention treatments as Bromhexine Hydrochloride Tablets, Arbidol Hydrochloride Granules, Recombinant Human Interferon α2b Spray; and the control as Arbidol Hydrochloride Granules and Recombinant Human Interferon α2b Spray. The accepted manuscript reported the intervention arm as Bromhexine Hydrochloride group and the control group as standard of care. All patients received antiviral drugs including arbidol hydrochloride granules and recombinant human interferon α2b spray. A total of 9 patients, 8 from the Bromhexine Hydrochlorid group and 1 from the control group, had treatment duration of less than 14 days because of early cessation with disease recovery. No patient in either group deteriorated during the observation period; all patients in both groups achieved clinical remission and negative SARS-CoV-2 results. |