Sofosbuvir/Ledipasvir and Nitazoxanide for Treatment of COVID-19

This study is an open-label, randomized, controlled trial. A total of 216 patients who are
recruited in 2 quarantine hospitals (15th of May hospital, Cairo, and Al Rajhi hospital,
Assiut), will be randomly assigned in a 1:1:1 ratio (72 patient in each treatment arm), to
receive either the fixed combination of Sofosbuvir/Ledipasvir (400 mg and 90 mg, orally)
once daily for 14 days, plus the standard care treatment regimen (SCT) for COVID-19
patients according to the Egyptian Ministry of Health (MOH) protocol (Group 1), or
nitazoxanide (500 mg, orally) four times per day for 14 days, plus STC (Group 2), or SCT
alone (Group 3). All treatment groups will be followed up by laboratory investigations and
PCR for SARS-CoV-2 virus at the time of enrollment, days 5, 8, 11, and 14. Supportive care
comprised, as necessary, supplemental oxygen, noninvasive and invasive ventilation,
antibiotic agents, vasopressor support, renal-replacement therapy, and extracorporeal
membrane oxygenation (ECMO). To ensure a balanced distribution of case severities in all
study groups, randomization will be stratified based on the case severity index issued by
WHO
(https://www.who.int/docs/default-source/coronaviruse/clinical-managemen…)
.

Written informed consent will be obtained from all patients or the patient's legal
representative if the patient is too unwell to provide consent. The trial will be conducted
in accordance with the principles of the Declaration of Helsinki and the Good Clinical
Practice guidelines of the International Conference on Harmonisation. The authors are
responsible for designing the trial and for compiling and analyzing the data. The authors
vouch for data completeness and accuracy and adherence to the trial protocol.

Inclusion Criteria:

- This study will include patients with confirmed COVID-19 infection and admitted to
COVID-19 quarantine hospitals. Included patients should be > 12 years old, with
creatinine clearance > 30 mL/ml, and without any malignancy. Patients with COVID-19
infection are classified clinically into mild, moderate, severe, and critical cases
according to the management guide for COVID-19 published by the Egyptian Ministry of
Health and Population. Mild cases are defined as patients in whom clinical symptoms
are mild, and no pneumonia manifestations can be found in imaging. Moderate cases are
defined as patients having symptoms such as fever and respiratory tract symptoms, etc.
and pneumonia manifestations can be seen in imaging. Severe cases are patients who
meet any of the following criteria; (a) respiratory rate > 30 breaths/min, (b) oxygen
saturations< 93% at a rest state, (c) arterial partial pressure of oxygen (PaO2)/
Fraction of inspired oxygen (FiO2)<300 mm Hg, or (d) patients with more than 50%
lesions progression within 24 to 48 hours in lung imaging should be treated as severe
cases. Finally, critical patients are those who are meeting any of the following
criteria; (a) occurrence of respiratory failure requiring mechanical ventilation, or
(b) the presence of shock; other organ failures that require monitoring and treatment
in the ICU. All patients with an established diagnosis of COVID-19 in Egyptian
quarantine hospitals at any clinical stage will be included in this study.

Exclusion Criteria:

- Patients < 12 years old.

- Pregnant females.

- Patients with renal impairment with creatinine clearance < 30 mL/min.

- Patients with malignancies particularly Hepatocellular Carcinoma (HCC).

- Patients using Favipiravir or Lopinavir-Ritonavir, as the co-administration of these
drugs with Sofosbuvir/Ledipasvir has not been studied.

- Patients with decompensated liver cirrhosis (Child-Pugh score B and C).