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Sofosbuvir/Ledipasvir and Nitazoxanide for Treatment of COVID-19

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ClinicalTrials.gov Identifier: NCT04498936
Recruitment Status : Completed
First Posted : August 5, 2020
Last Update Posted : November 12, 2020
Sponsor:
Collaborator:
Helwan University
Information provided by (Responsible Party):
Mohammed Ahmed Medhat, Assiut University

Brief Summary:
The efficacy of treating COVID-19 infection by using Sofosbuvir/Ledipasvir and Nitazoxanide will be examined. Included patients will be into 3 groups. The 1st group will receive Sofosbuvir/Ledipasvir plus the standard care treatment (SCT). The 2nd group will take Nitazoxanide and SCT, while the 3rd group will receive only SCT. Then the clinical improvement and the rate of PCR change from positive to negative will be evaluated in each group.

Condition or disease Intervention/treatment Phase
COVID Drug: Sofosbuvir and Ledipasvir Drug: Nitazoxanide Phase 4

Detailed Description:

This study is an open-label, randomized, controlled trial. A total of 240 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 (80 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-management-of-novel-cov.pdf).

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy of Adding Sofosbuvir/Ledipasvir Combination, or Nitazoxanide to the Standard of Care in Treatment of COVID-19: A Randomized Controlled Trial
Actual Study Start Date : July 15, 2020
Actual Primary Completion Date : October 30, 2020
Actual Study Completion Date : October 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sofosbuvir/Ledipasvir
This group will receive a 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.
Drug: Sofosbuvir and Ledipasvir
Evaluate the efficacy of Sofosbuvir/Ledipasvir in treatment of COVID-19
Other Name: Treatment

Experimental: Nitazoxanide
This group will receive nitazoxanide (500 mg, orally) four times per day for 14 days, plus the standard care treatment regimen (SCT) for COVID-19 patients according to the Egyptian Ministry of Health (MOH) protocol.
Drug: Nitazoxanide
Evaluate the efficacy of Nitazoxanide in treatment of COVID-19
Other Name: Treatment

No Intervention: Standard care treatment
This group will receive only the standard care treatment regimen (SCT) for COVID-19 patients according to the Egyptian Ministry of Health (MOH) protocol.



Primary Outcome Measures :
  1. Change of PCR from positive to negative [ Time Frame: 2 weeks ]
    The PCR will be done at time of recruitment, day 5, 8, 11, and 14. The time taken to have negative will be measured in each group.

  2. Clinical improvement [ Time Frame: 2 weeks ]
    Clinical improvement will be measured by detection of downgrading of cases severity according to the World Health Organization case severity classification.


Secondary Outcome Measures :
  1. Adverse events [ Time Frame: 2 weeks ]
    All patients will be asked about any possible adverse effects that they may suffer from taken drugs during their follow up. Any mentioned side effect will be reported. Drug discontinuation and it cause will be also reported if it happened.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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-management-of-novel-cov.pdf).

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04498936


Locations
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Egypt
15th May Hospital
Helwan, Cairo, Egypt
Assiut University Hospital
Assiut, Egypt, 71515
Sponsors and Collaborators
Assiut University
Helwan University
Investigators
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Principal Investigator: Mohammed A Medhat, PhD Assiut University
Study Chair: Mohamed El Kassas, PhD Helwan University
Principal Investigator: Haidi K Ramadan, PhD Assiut University
Additional Information:
Publications:
Ju, J., et al., Nucleotide Analogues as Inhibitors of Viral Polymerases. bioRxiv, 2020: p. 2020.01.30.927574.
Padmanabhan, S., Potential dual therapeutic approach against SARS-CoV-2/COVID-19 with Nitazoxanide and Hydroxychloroquine. 2020.

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Responsible Party: Mohammed Ahmed Medhat, Lecturer of Tropical Medicine and Gastroenterology, Assiut University
ClinicalTrials.gov Identifier: NCT04498936    
Other Study ID Numbers: COVID-19 treatment
First Posted: August 5, 2020    Key Record Dates
Last Update Posted: November 12, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Sofosbuvir
Ledipasvir
Ledipasvir, sofosbuvir drug combination
Nitazoxanide
Antiviral Agents
Anti-Infective Agents
Antiparasitic Agents