Covid-19 living Data

Hydroxychloroquine + Azithromycin vs Standard care/Placebo (RCT)

Mild outpatients

FOREST PLOTS -2021-09-24

Studies description

Trial NCT04349592
Publication Q-PROTECT - Omrani A, EClinicalMedicine (2020) (published paper)
Dates: 2020-04-13 to 2020-08-01
Funding: Public/non profit (Hamad Medical Corporation (government health service of the State of Qatar))
Conflict of interest: No

Methods
	RCT Blinding:
	Location : Multicenter / Qatar Follow-up duration (days): 21
Inclusion criteria	Positive Covid test (PCR) used during routine care (i.e. not as part of Q-PROTECT) Patient is in HMC facility for Covid-positive quarantine patients of low acuity (i.e. not requiring hospitalization or antiviral therapy by current Ministry of Public Health guidelines) most cases are anticipated to be healthy young expatriates who cannot be home-quarantined Age at least 18
Exclusion criteria	Treating physician judges patient not appropriate for study participation for any reason Known retinal disease or macular degeneration Psoriasis On tamoxifen for breast cancer Age <18 Breastfeeding or pregnancy (patient-reported pregnancy status is sufficient) Hypersensitivity to chloroquine or HC or AZ History of or known QT prolongation EKG required before study entry and on each visit during the subject’s first seven days on protocol, during the time period HC is being taken Baseline QTc >480 if QRS width normal QTc >510 if QRS >120 Known G6PD deficiency, porphyria, or retinopathy Known hepatic or renal impairment/disease (or abnormality on liver/renal testing at study day 1) Low magnesium or low potassium (by testing on day 1) Current (pre-study) therapy with antimalarial or dapsone Current (pre-study) therapy with antiviral agents (e.g. oseltamivir) Tisdale38 score exceeding 6 as tallied below (based on ACC recommendations)
Interventions
	Treatment HCQ+AZM Hydroxychloroquine: 200 mg orally 3 times a day for 7 days. Azithromycin: 500 mg orally on day 1 followed by 250 mg orally once a day for the next 4 days. Hydroxychloroquine 200 mg orally 3 times a day for 7 days
	Control Placebo
Participants
	Randomized participants : HCQ+AZM=152 Hydroxychloroquine=152 Placebo=152
	Characteristics of participants N= 456 Mean age : NR 449 males Severity : Mild: n= 456/ Asymptomatic: n=0
Primary outcome
	In the register Proportion of virologically cured (PCR-negative status) as assessed on day six [ Time Frame: Day 6 ]
	In the report Virologic cure (PCR-negative status) as assessed on day six.
Documents avalaible	Protocol Yes. In English Statistical plan NR Data-sharing willing stated in the publication:
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 article, the trial registry and study protocol were used for data extraction and assessment of risk of bias. No statistical analysis plan was available. There were no substantive differences between the published article, the current trial registration and the study protocol in terms of procedures, population or treatments. The trial registry was changed near to end of recruitment to include outcomes not included in the original entry and the study protocol is not dated, but the data extracted are not affected. The study achieved its pre-stated sample size. Although open to both sexes and conducted in Qatar, the study population was overwhelmingly male and no Qataris were included, reflecting the country’s workforce.

Trial RBR-95yjmq
Publication Rodrigues C, Int J Antimicrob Age (2021) (published paper)
Dates: 2020-04-12 to 2020-05-13
Funding: Private (Diagnósticos da América S.A. (Dasa), Ímpar Serviços Hospitalares S.A., and DNA Capital Foundation.)
Conflict of interest: No

Methods
	RCT Blinding: double blinding
	Location : Single center / Brazil Follow-up duration (days): 21
Inclusion criteria	1) Aged between 18 and 65 years 2) mild symptoms suggestive of COVID-19 (two or more of the following: cough, fever, shortness of breath, nausea/vomiting, diarrhea, body aches, weakness/fatigue, headache, sore throat, runny nose/congestion, sudden gustatory or olfactory loss) with an interval from symptoms onset to enrollment of 2 to 5 days 3) detection of viral RNA in naso/oropharyngeal swabs through a real-time reverse-transcription polymerase chain reaction 4) Not requiring hospital admittance 5) Consenting to study participation
Exclusion criteria	1) known hypersensitivity to HCQ or azithromycin (AZT) 2) pre-existing pulmonary disease, history of immunosuppression, active cancer diagnosis 3) pregnancy or lactation 4) history of cardiac abnormalities or QTc prolongation (QTc > 480 ms) 5) known glucose-6-phosphate dehydrogenase (G6PD) deficiency 6) patients requiring hospital admittance 7) patients with inadequate hematological parameters, heart, renal, or liver function
Interventions
	Treatment HCQ+AZM HCQ: two 200 mg capsules twice a day for seven days + AZM: Initial dose: one 500 mg capsule on day 1 - Maintenance dose: one 250m mg capsule/day for 4 days
	Control Placebo
Participants
	Randomized participants : HCQ+AZM=42 Placebo=42
	Characteristics of participants N= 84 Mean age : NR 50 males Severity : Mild: n= 84/ Asymptomatic: n=0
Primary outcome
	In the register Time to negative viral load from the beginning of treatment and up to 9 days
	In the report Time (days) to viral clearance within a 9-day evaluation period following enrollment following the onset of symptoms and the study enrollment dates.
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Not reported
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 article, the retrospective study registry was used in data extraction and risk of bias assessment. Neither protocol nor statistical analysis plan was available There is no change from the trial registration in the intervention and control treatments. The primary outcome indicated in registry reflects the primary outcome reported in the paper. Some secondary outcomes in the registry (radiographic response, concomitant medication to manage symptoms, adverse events) were not reported or not fully reported. The study achieved the target sample size declared in the methods (n = 84), but not that in the registry (n = 108). Risk of bias assessment was updated on May 15th 2022 after quality control.