| Besarab 2015 |
| Random sequence generation |
Low risk |
Treatment was assigned according to a randomization code provided by the statistical contract research organization |
| Allocation concealment |
Low risk |
Study drugs were not dispensed in containers identifiable by subject as containing active or placebo capsules |
| Blinding of participants and personnel |
High risk |
The study was single-blinded. Drugs were administered to subjects in a manner that did not reveal treatment assignment to the subjects |
| Blinding of outcome assessment |
High risk |
The study was single-blinded, and the dose varied during the study |
| Incomplete outcome data |
Low risk |
The details of incomplete outcome have been stated |
| Selective reporting |
Low risk |
All parameters have been reported |
| Other bias |
High risk |
The study was supported by pharmaceutical company |
| Chen 2017 |
| Random sequence generation |
Unclear risk |
Not reported |
| Allocation concealment |
Unclear risk |
Not reported |
| Blinding of participants and personnel |
Low risk |
The study was a double-blinded trial, and no breaking of randomization was reported |
| Blinding of outcome assessment |
Unclear risk |
Not reported |
| Incomplete outcome data |
Low risks |
Five patients withdrew consent. Three patients dropped out because of adverse events. Two patients lacked of efficacy were excluded |
| Selective reporting |
Low risk |
All collected parameters have been reported |
| Other bias |
High risk |
The study was supported by pharmaceutical company |
| Akizawa 2019 |
| Random sequence generation |
Unclear risk |
It is unclear how were the random sequence generated |
| Allocation concealment |
Low risk |
Dynamic allocation was conducted using a biased-coin minimization approach |
| Blinding of participants and personnel |
Low risk |
The study was double-blinded, and no breaking of randomization was reported |
| Blinding of outcome assessment |
Unclear risk |
Not reported |
| Incomplete outcome data |
Low risk |
All dropped-out patients have been reported |
| Selective reporting |
Low risk |
All the results were reported |
| Other bias |
High risk |
The study was supported by pharmaceutical company |
