Covid-19 Living Data

Trial NCT04392973
Publication Bosaeed M, Infect Dis Ther, 2021 (published paper)
Dates: 2020-05-21 to 2021-01-26
Funding: Public/non profit (King Abdullah International Medical Research Center, Saudi Arabia.)
Conflict of interest: No

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / Saudi Arabia Follow-up duration (days): 90
Inclusion criteria	Should be at least 18 years of age; Male or nonpregnant female; Diagnosed with COVID-19 by PCR confirmed SARS-coV-2 viral infection; Able to sign the consent form and agree to clinical samples collection (or their legal surrogates if subjects are or become unable to make informed decisions); Moderate or Severe COVID-19, defined as oxygen saturation (SaO2) of B 94% while breathing ambient air or significant clinical symptoms with chest x-ray changes; patients had to be enrolled within 10 days of disease onset
Exclusion criteria	Patients who are pregnant or breastfeeding; Will be transferred to a non-study site hospital or discharged from hospital within 72 hours; Known sensitivity/allergy to hydroxychloroquine or Favipiravir; Current use of hydroxychloroquine for another indication; Prior diagnosis of retinopathy; Prior diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency; Major comorbidities increasing the risk of study drug including: i. Hematologic malignancy, ii. Advanced (stage 4-5) chronic kidney disease or dialysis therapy, iii. Known history of ventricular arrhythmias, iv. Current use of drugs that prolong the QT interval, Severe liver damage (Child-Pugh score≥C, AST> 5 times the upper limit), HIV; The investigator believes that participating in the trial is not in the best interests of the patient, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues); Clinical prognostic non-survival, palliative care, or in deep coma and no have response to supportive treatment within three hours of admission; Patient with irregular rhythm; Patient with a history of heart attack (myocardial infarction); Patient with a family history of sudden death from heart attack before the age of 50; Take other drugs that can cause prolonged QT intervalelectrocardiogram (ECG) of > 490 ms; Patient who is receiving immunosuppressive therapy (cyclosporin) which cannot be switched to another agent or adjusted while using the investigational drug; Gout/history of Gout or hyperuricemia (above the ULN), hereditary xanthinuria or xanthine calculi of the urinary tract.
Interventions
	Treatment Favipiravir+Hydroxychloroquine Favipavir. Initial dose: 1800 mg orally 2 times a day for 1 day. Maintenance dose: 800 mg orally 2 times a day for 9 days. Hydroxychloroquine. Initial dose: 400 mg 2 times a day for 1 day. Maintenance dose: 200mg 2 times a day for 4 days.
	Control Standard care ( / ) Definition of Standard care: "Treatment that is accepted by medical experts as a proper treatment for Covid-19 disease. Standard care comprised of, as necessary, supplemental oxygen, noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, extracorporeal membrane oxygenation (ECMO), and antiviral therapy except Favipiravir. Also, it may include intravenous fluids and medications for symptoms relief", "The use of glucocorticoids, other immunomodulators, and antibiotic agents were allowed, and all were recorded throughout the hospitalisation. "
Participants
	Randomized 268 participants (n₁=132 / n₂= 136)
	Characteristics of participants N=268 Mean age : 52.6 103 males Severity : Mild: n=19 / Moderate: n=190/ Severe: n=39 Critical: n=6
Primary outcome
	In the register Clinical Improvement [ Time Frame: 28 days ] The primary endpoint is the time to clinical improvement, defined as the time from the randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first.
	In the report Time to clinical improvement, defined as the time from randomisation to an improvement of two points (from the status at randomisation) on a seven-category ordinal scale or live discharge from the hospital, whichever came first.
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated
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 the published/pre-print article, the study registry, statistical analysis plan and the protocol were used in data extraction and risk of bias assessment. The study did not achieved the target sample size specified in the trial registry. There is no change from the trial registration in the intervention and control treatments. The registry primary outcome reflects the reported primary outcome. Some outcomes from the report are not pre-specified in the registry (e.g. mortality, time to death). Adverse events were reported but not extracted. On 10th of August, 2021, this study was updated based on the published report.