Trial DRKS00022203
Publication Yakoot M, SSRN, 2020 (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 | Men or women aged 18-75 years; Subjects or their legal representatives have signed the informed consent form (ICF); laboratory-confirmed Symptomatic COVID-19 (SARS-CoV-2 infection) as determined by polymerase chain reaction (PCR) assay in any specimen collected < 72 hours prior to randomization and any clinical severity category of the following: A. Mild: mild clinical symptoms with no picture of pneumonia in CT, but positive 2019-nCoV2 in throat/nasal swabs. B. Moderate: fever, respiratory symptoms, etc., pneumonia visible in CT. C. Severe (Not Critical): meeting any of the following criteria: (a) Respiratory distress, RR≥30 times/min; (b) Finger oxygen saturation ≤93% in rest state; (c) Arterial partial pressure of oxygen / concentration of fractional inspired oxygen (PaO2/FiO2) ≤400mmHg and > 200mmHg under oxygen inhalation. |
Exclusion criteria | Patients with pneumonia due to other etiology; Critically severe COVID19 ARDS cases Requiring invasive mechanical ventilation at screening; Patients who have severe concomitant illness that affects survival or course of the disease, including uncontrolled malignant tumor, HIV, blood dyscrasia, active bleeding or patients with shock/or multiple organ failure at screening; Pregnant 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); Patients with 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 SOF/DCV: 400/60 mg orally once daily for 10 days |
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Control
Standard care Definition of Standard care: Standard of care (as per the Egyptian Ministry of Health (MOH) protocol which was given to all patients included: Plaquenil (Hydroxychloroquine) which was given in a dose of 4 tablets of 200 mg, on Day 1 followed by 2 tablets daily from day 2 through day 5. Azithromycin was given in a daily dose of 500 mg for 5 days. Full nutritional support with balanced diet and multivitamin and zinc supplements with vitamin C and D were offered to all patients. Other drugs were given according to each patient clinical condition and included: analgesic-antipyretic (acetaminophen 500 mg as needed); cough mixtures: either or a cough suppressant with low dose dextromethorphan (for irritating dry cough) or a mixture of a mucolytic (ambroxol) combined with a small theophylline dose (Farcosolvin) aiming to provide enhancing effect on muco-ciliary escalation and surfactant release from type-2 alveolar cells. Conservative IV fluid management if indicated and oxygen therapy by face mask, nasal cannula with treatment escalation to high flow rate Oxygen, up to mechanical ventilation were offered promptly as needed when any case deteriorated in accordance with the ministry of health protocol for critically severe cases. Parenteral antibiotics were allowed to be added for any patient with suspected superadded bacterial infection according to the MOH protocol for serious/critical infections. Heparin/low molecular weight heparin/ or novel oral anticoagulants in a low prophylactic dose were offered for any patient with significantly high D-Dimer > 500 microgram/Liter, and allowed to be escalated to full therapeutic anticoagulant dose for any case with high clinical or imaging probability of thromboembolism. Duration : 10 days | |
Participants | |
Randomized 89 participants (n1=44 / n2= 45) | |
Characteristics of participants N=89 Mean age : NR 38 males Severity : Mild: n=12 / Moderate: n=61/ Severe: n=16 Critical: n=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. 2. Time to clinical recover | |
In the report Clinical recovery within 21 days following enrolment | |
Documents available |
Protocol NR Statistical plan NR Data-sharing stated NR |
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 was used in data extraction and assessment of risk of bias. Neither the study protocol nor statistical analysis plan was available. There were no substantive differences between the pre-print article and the trial registry in study procedures, population or treatments. Due to logistics constraints nasal/throat swabs for PCR test were not taken as frequent to allow for testing time to viral negativity, which was an outcome in the trial registry. The registry describes the study as multi-center but the study reported was single-center. The study achieved its pre-stated sample size. |