Note: The risk of bias by domain corresponds to the highest risk of bias among outcomes by domain.
The overall risk of bias corresponds to the overall highest risk of bias assessed among outcomes.
| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
Quote: “Patients were randomly assigned into two arms of the study by permuted block randomization method. Six quadruple blocks including AABB, ABAB, ABBA, BBAA, BABA, and BAAB were determined, and a random number table was utilized to select one of the six predefined blocks for each of the four patients. According to the order specified in each block, two patients received treatment A (treatment with LVM) and two patients received treatment B (treatment without LVM). The appropriate number of vials of open-label study drugs were assigned to the patient. Sites did not
have access to the randomization list and were unaware of the treatments sequence. At the health center, study medication was distributed according to the random number allocated to each participant. The research pharmacies held this list, and statisticians verified that the randomization sequence was followed.”
Comment: Allocation sequence random. Allocation sequence concealed Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Low |
Quote: “open-label”
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. In the outpatient setting, we consider no important cointerventions of interest. Hence, no deviation arose because of the trial context. Our analysis for the binary outcome is an intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcomes: Hospitalization or death. Mortality (D28). Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: 507 participants randomized; 365 participants analyzed.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 68/74 patients were excluded post-randomization from the treatment/control arms; 16/18 didn't start the treatment (6/7 withdrew consent, 5/4 had a protocol violation); 52/56 had a negative COVID-19 PCR result; 9/10 stopped treatment early (4/5 lost to follow up, 1/0 adverse event, 2/4 hospitalization, 2/1 nonadherence). Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome because of similar proportions of missing data between arms. Risk assessed to be some concerns for the outcomes: Hospitalization or death. Mortality (D28). Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Unblinded study (outcome assessor) MORTALITY Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). HOSPITALIZATION OR DEATH For this outcome, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment. Risk assessed to be low for the outcomes: Hospitalization or death. SERIOUS ADVERSE EVENTS The authors reported on serious adverse events that may contain both clinically- and laboratory-detected events, which can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcomes: Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The registry (dated March 28, 2021) was available.
Outcome not pre-specified: the measurement of the primary outcome was to be by Visual Analogue Scale (VAS), however Visual Numeric Scale (VNS) was reported in the paper. The time point of the primary and secondary outcomes were listed as days 1,2,3,4,14,28 in the registry but reported on days 3,5,7,9,14,28 in the paper. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial not analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Hospitalization or death. Mortality (D28). Serious adverse events. |
| Overall risk of bias |
Some concerns |