Covid-19 Living Data

Trial DRKS00022203
Publication Yakoot M, medRxiv (2022) (preprint)
Dates: 2020-06-20 to 2020-09-30
Funding: Private (PHARCO CORPORATE)
Conflict of interest: Yes

Methods
	RCT Blinding: Unblinded
	Location : Single center / Egypt Follow-up duration (days): 21
Inclusion criteria	Between 18 and 75 years of age presented with laboratory-confirmed COVID-19 infection as determined by polymerase chain reaction (PCR) assay in any specimen collected within 72 hours prior to randomization symptomatic at screening presenting with clinical manifestations under one of three severity categories - Mild, Moderate or Severe disease. Mild was defined as having mild symptoms with no picture of pneumonia in Computerized Tomography scan (CT-scan). Moderate was defined as having moderate fever and respiratory symptoms plus evidence of pneumonic lesions in CT-scan. The severe disease (but Not Critical) included patients with laboratory confirmed COVID-19, presenting at baseline by any of the following criteria: respiratory distress and respiratory rate (RR)≥30 times/min Finger oxygen saturation ≤93% in rest state Arterial partial pressure of oxygen / concentration of fractional inspired oxygen (PaO2/FiO2) ≤300mmHg and > 200mmHg under oxygen inhalation not necessitating ICU admission or mechanical ventilation
Exclusion criteria	Refusal or inability to sign the informed consent form pneumonia due to other etiology patients with acute respiratory distress syndrome requiring invasive mechanical ventilation at screening late presentation of patient after 10 days from the appearance of symptoms severe concomitant illness that affects survival or course of the disease including uncontrolled malignancy, HIV, active bleeding, shock/or multiple organ failure at screening pregnancy or lactating females hypersensitivity or contraindication to any of the experimental drugs used in the study (Prolonged QT syndrome, G6PD deficiency, psoriasis, retinal damage or others) decompensated liver cirrhosis or abnormal liver enzyme tests above three times the upper limit values (alanine aminotransferase – (ALT) and aspartate aminotransferase (AST) renal dysfunction (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73m2)
Interventions
	Treatment Sofosbuvir-Daclatasvir 400 mg sofosbuvir + 60 mg daclatasvir orally once a day for 10 days
	Control Standard care
Participants
	Randomized participants : Sofosbuvir-Daclatasvir=44 Standard care=45
	Characteristics of participants N= 89 Mean age : NR 38 males Severity : Mild: n=12 / Moderate: n=61 / Severe: n=16 Critical: n=0 Number of vaccinated participants: 0
Primary outcome
	In the register 1. Proportion of clinical recovery (composite) within 14 & 21 days (Normalization of fever (≤37.2 °C oral), Respiratory rate (≤24/minute on room air), Oxygen saturation (≥94% on room air)), sustained for at least 24 hours (using Exact test with Boot-Strapping) ; 2. Time to clinical recovery (composite) [Time frame: 21 days after randomization (using Kaplan Meier curve and Cox-regression) ; 3. Time to viral negativity assessed twice 48 hours apart (log10 viral load assessed by reverse transcription-PCR) during hospital stay (Kaplan Meier curve and Cox-regression) ; 4. Mean change in Clinical status using 8 point ordinal scale [Day 3 through Day 14, 21 (using Repeated measure Factorial ANOVA test]: 1) Death; 2) Hospitalized, on invasive ventilation or ECMO; 3) Hospitalized, on NIV or HFO2; 4) Hospitalized with oxygen supplement; 5) Hospitalized, not requiring oxygen but need medical care; 6) Hospitalized, not requiring supplemental oxygen or ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized with normal activity.
	In the report 1) Proportions-of and 2) time-to-clinical recovery within the 21day time-frame following enrolment
Documents available	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Yes
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 pre-print article, the trial registry, protocol, statistical analysis plan and supplementary appendices were used in data extraction and assessment of risk of bias. In the registry the study had three arms (sofosbuvir/daclatasvir + SOC, hydroxychloroquine + SOC, and SOC alone), but the article reports on two arms (sofosbuvir/daclatasvir + SOC, and SOC alone, with both arms receiving hydroxychloroquine as part of SOC). The primary outcome indicated in registry reflects the primary outcome reported in the paper.