Therapeutic Application of Chloroquine in Clinical Trials for COVID-19

Divya RSJB Rana; Santosh Dulal

is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.22.20040964 doi: medRxiv preprint T 0 4 3 0 3 2 9 9 8 H C Q : A r m 1 : 8 0 0 m g / d a y , 1 0 d a y s w i t h d i f f e r e n t a n t i v i r a l s ; A r m 2 , 6 , 7 : Most of the trials used oral chloroquine (68.2%, 15/33) or hydroxychloroquine (68.2%, 15/33) singly as treatment options, followed by chloroquine in combination with other antivirals ((13.6%, 3/33), hydroxychloroquine with azithromycin (9.1%, 2/33), chloroquine as aerosols (9.1%, 2/33), chloroquine with azithromycin (4.5%, 1/33) and hydroxychloroquine with other antivirals (4.5%, 1/33) ( Table 1 ). The maximum quantity of chloroquine given was 12 g in a period of 10 days (NCT04323527) and the lowest reported was 2.1 g aerosolized chloroquine (ChiCTR2000029975) in a duration on 7 days. Similarly, the maximum quantity of hydroxychloroquine given was 12.4 gm in a duration of 14 days (ChiCTR2000029868) and the lowest amount was 2 gm in a period of 5 days (NCT04261517). Only one of the two trials using aerosolized chloroquine phosphate stated the dosage. It was 2.1 gm in a period of 7 days (ChiCTR2000029975). All 12894 study patients are planned to be enrolled in 33 trials. Twelve trials registered in the US registry didn't have details about sample size allocation into individual intervention arms. For the remaining 5842 individuals in 21 trials with information of sample sizes, 1199 patients are to get chloroquine alone, 1050 are to get hydroxychloroquine alone 159 got chloroquine with other drugs, 25 are to get aerosolized chloroquines, 1320 are to get conventional treatments or placebo, and 2089 are to get other antivirals. All of the active or placebo interventions also get conventional treatments or the standard care. Out of the 33 clinical trials, 4 reported that they were not designed to be randomized, two were single arm studies and didn't require randomization and 27 reported using some kind of randomization. Out of total, three-fourth (91%, 30/33) studies set 18 years old as lower age limit for inclusion criteria while two trials used 16 years, and one trial used 30 years. Similarly, upper age limit ranged from 65 to 100 years of age. All trials reported enrolling both genders in the study.