Covid-19 living Data

Sofosbuvir/ledipasvir vs Standard care (RCT)

Hospitalized patients

FOREST PLOTS -2022-05-16

Studies description

Trial NCT04530422
Publication Elgohary M, J Med Life (2022) (published paper)
Dates: 2020-04-15 to 2020-06-30
Funding: Not reported/unclear (None)
Conflict of interest: No

Methods
	RCT Blinding: single blinding
	Location : Single center / Egypt Follow-up duration (days): 21
Inclusion criteria	Pneumonic patients with SARS-COV-2 infection confirmed to be positive by RT-PCR demonstrated moderate cases criteria: fever (measured temperature of at least 38 °C), respiratory symptoms (cough, shortness of breath), and imaging-confirmed pneumonia age more than 18 and less than 75 years old Female patients enrolled in the study should have no planned pregnancy for six months, with the administration of proper contraceptive measures within 30 days from the first therapeutic dose of the investigational drugs informed consent no participation in other clinical trials within 30 days from the last administration of the study drugs.
Exclusion criteria	Mild COVID-19 patients who had mild symptoms without evidence of viral pneumonia or hypoxia and severe COVID-19 patients who met one of the following conditions: (1) Respiratory rate (R.R.) ≥ 30 times/min (2) SaO2/SpO2 ≤ 93% in resting-state (3) arterial partial pressure of oxygen (PaO2)/concentration of oxygen (FiO2) ≤ 300 mmHg Critical COVID-19 patients with one of the following conditions: (1) respiratory failure and need mechanical ventilation (2) shock (3) other organ failure combined with ICU treatment (4) severe liver disease (such as child Pugh score ≥ C, AST > five times upper limit) patients with contraindications specified for any drugs used in the study or who received antiviral eradication therapy for hepatitis C or B viruses within the previous six months
Interventions
	Treatment SOF/LDP Once daily for 15 days. Dose not reported.
	Control Standard care
Participants
	Randomized participants : SOF/LDP=125 Standard care=125
	Characteristics of participants N= 250 Mean age : NR 59 males Severity : Mild: n=0 / Moderate: n=250 / Severe: n=0 Critical: n=0
Primary outcome
	In the register Therapeutic success (cured) [Time Frame: 21 days]; 28 days in hospital mortality [Time Frame: 28 days]
	In the report Cure rate over time, length of hospital stay and the incidence of serious adverse events that lead to ICU admission or death
Documents avalaible	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 and published articles, the trial registry was used in data extraction and assessment of risk of bias. Neither study protocol nor statistical analysis plan was available. The study registration was retrospective (dated August 28, 2020 compared to study recruitment start date of April 15, 2020 as reported in the preprint). The registry reports treatment with Sofosbuvir plus Ledipasvir once daily for 15 to 21 days, whereas the article reports once daily for 15 days. The dosage of Sofosbuvir plus Ledipasvir was not reported in either the article or the registry. Primary outcomes in the report (cure rate over time, length of hospital stay and incidence of SAEs that lead to ICU admission or death) differed from those in the registry (cure defined as virological clearance in 2 samples at least 24 hours apart at 21 days, mortality at 28 days). There were also differences between secondary outcomes in the report (time to virological cure as detected by PCR and chest CT findings, laboratory outcomes) and the registry (clinical failure of treatments by PCR, length of hospital stay, side effects known to be related to the medication). Adverse events are not reported. This study was published on May 11th, 2022 with data extracted from the published report.

Trial IRCT20100228003449N29
Publication Nourian A, Acta Biomed (2020) (published paper)

Funding: Mixed (Tehran University of Medical Sciences. SOF/LDP donated from Zistdaru Danesh Co.)
Conflict of interest: No

Methods
	RCT Blinding: Unblinded
	Location : Single center / Iran Follow-up duration (days): 14
Inclusion criteria	Adult patients (≥18 years old) highly suspected (according to the clinical signs/symptoms and imaging findings) or confirmed (a positive PCR of pharyngeal or nasopharyngeal samples) COVID-19 who were admitted to medical wards of the hospital
Exclusion criteria	History of drug allergy decompensated cirrhosis severe COVID-19 patients under hemodialysis pregnant and lactating women
Interventions
	Treatment SOF/LDP 400/100 mg orally once daily for 10 days
	Control Standard care
Participants
	Randomized participants : SOF/LDP=45 Standard care=45
	Characteristics of participants N= 90 Mean age : NR 0 males Severity : Mild: n=* / Moderate: n=* / Severe: n=* Critical: n=0
Primary outcome
	In the register Response to the treatment (improvement of patients' chief complaint, abnormal paraclinic and radiologic findings); Gastrointestinal complications; Cutaneous complications; Neurological complications; Renal complications; Hematological complications
	In the report Clinical response; Time to clinical response
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 trial registry was used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan was available. The study achieved the target sample size specified in the trial registry. The intervention dose was slightly different in the trial registration compared to the publication. There were some differences in the outcomes reported, the definition of outcomes and outcome timepoint between the published report and the trial registry.