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Efficacy and Safety of Direct Anti HCV Drugs in the Treatment of SARS-COV-2 (COVID-19) (CCOVID-19)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04535869
Recruitment Status : Unknown
Verified August 2020 by Mahmoud Elbendary, Mansoura University.
Recruitment status was:  Recruiting
First Posted : September 2, 2020
Last Update Posted : February 24, 2021
Sponsor:
Information provided by (Responsible Party):
Mahmoud Elbendary, Mansoura University

Tracking Information
First Submitted Date  ICMJE August 28, 2020
First Posted Date  ICMJE September 2, 2020
Last Update Posted Date February 24, 2021
Actual Study Start Date  ICMJE December 28, 2020
Estimated Primary Completion Date April 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 31, 2020)
rate of virological cure by Rt -PCR for COVID -19using the triple therapy as compared to standard treatment [ Time Frame: for every case must be done after 2 weeks from the start of treatment. ]
All PCR for COVID must be negative
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 31, 2020)
resolution of pneumonia BY high resolution Computed tomography [ Time Frame: Computed tomography must be done after 2 weeks to detect resolution of pneumonia ]
clinical status as assessed by earlier resolution of pneumonia in the intervention arm when compared to the control group
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Direct Anti HCV Drugs in the Treatment of SARS-COV-2 (COVID-19)
Official Title  ICMJE Efficacy and Safety of Direct Anti HCV Drugs in the Treatment of SARS-COV-2 (COVID-19)
Brief Summary

COVID 19 which started from a zoonotic transmission related to crowded markets was confirmed to have a high potential for transmission to close contacts on 20 January 2020 by the National Health Commission of China and it was announced as a pandemic by the WHO on 11 March 2020.

There is currently no clinically proven specific antiviral agent available for SARS-CoV-2 infection. Supportive treatment, including oxygen therapy, conservation fluid management, and broad-spectrum antibiotics to cover secondary bacterial infection, remains the most important management strategy.

Interestingly, sofosbuvir has recently been proposed as an antiviral for the SARS-CoV-2 based on the similarity between the replication mechanisms of the HCV and the coronaviruses.

Aim of our study is to assess the safety and efficacy of of the addition of HCV treatment to the standard regimen for the treatment of patients according to MOHP protocol.

Detailed Description

SARS-CoV-2 infection have a wide clinical spectrum ranging between asymptomatic infection, mild upper respiratory tract symptoms, and severe viral pneumonia (fever, malaise, dry cough, shortness of breath, and respiratory distress) that may result in respiratory failure and finally death.

There is currently no clinically proven specific antiviral agent available for SARS-CoV-2 infection. Supportive treatment, including oxygen therapy, conservation fluid management, and broad-spectrum antibiotics to cover secondary bacterial infection, remains the most important management strategy.

For direct antiviral treatment of SARS-CoV-2, the China International Exchange and Promotive Association for Medical and Health Care (CPAM) recommended usage of lopinavir; ritonavir. Their recommendation was based on weak evidence from retrospective cohort, historically controlled studies, case reports, and case series reporting a clinical benefit of lopinavir; ritonavir in the management of other coronavirus infection [i.e., SARS-CoV 1 and Middle East respiratory syndrome coronavirus (MERS-CoV)] .

However, the first randomized clinical trial with lopinavir/ritonavir demonstrated no benefit over standard care in 199 hospitalized adults with severe COVID-19. There is no evidence to support the use of other antiretrovirals, including protease inhibitors; indeed, structural analysis demonstrates no darunavir binding to COVID-19 protease A group of Korean physicians experienced in SARS-CoV-2 infected patients' treatment developed recommendations for the treatment of COVID-19. According to them, antiviral medications lopinavir 400 mg; ritonavir 100 mg, or chloroquine is considered to be used in older patients or patients with chronic health conditions and life-threatening symptoms. If chloroquine is unavailable, hydroxychloroquine is recommended. Both of them have reported the ability of inhibition of SARS-CoV-2 in vitro.

CPAM guidelines included them as they were associated with reduced progression of the disease and decreased duration of symptoms. In an open-label study of 36 patients with COVID-19, the use of hydroxychloroquine (200 mg three times per day for 10 days) was associated with a higher rate of undetectable SARS-CoV-2 RNA on nasopharyngeal specimens at day 6 compared with no specific treatment (70 versus 12.5 percent). In this study, the use of azithromycin in combination with hydroxychloroquine appeared to have an additional benefit, but there are methodologic concerns about the control groups for the study, and the biologic basis for using azithromycin in this setting is unclear. In the United States, the FDA issued an emergency use authorization to allow the use of these agents in adolescents or adults hospitalized for COVID-19.

One of the studies done on SARS-COV-1 strongly suggested that using ribavirin as therapy should be reconsidered until further animal studies clarify the effects of ribavirin on cytokine and chemokine profiles during infection and until ribavirin can be demonstrated to have a significant effect on reducing viral replication in vivo. Data from a molecular docking experiment using the SARS-CoV-2 RNA dependent RNA polymerase (RdRp) model identified the tight binding of sofosbuvir and ribavirin to the coronavirus RdRp, thereby suggesting possible efficacy of sofosbuvir and ribavirin in treating the COVID-19 infection.

A three-dimensional model of the SARS-CoV-2 (aka 2019-nCoV) 3C-like protease (3CL ) was prepared then performed virtual screening for purchasable drugs checking the actions, targets, and side effects of the 16 candidates. Velpatasvir and ledipasvir are examples of these drugs ( which are inhibitors of the NS5A protein of the hepatitis C virus (HCV). Both are marketed as approved drugs in combination with sofosbuvir, which is a prodrug nucleotide analog inhibitor of RNA-dependent RNA polymerase (RdRp, or NS5B).

Interestingly, sofosbuvir has recently been proposed as an antiviral for the SARS-CoV-2 based on the similarity between the replication mechanisms of the HCV and the coronaviruses.

Based on this data it was suggested that these dual-component HCV drugs, Epclusa (velpatasvir/sofosbuvir) and Harvoni (ledipasvir/sofosbuvir), may be attractive candidates to repurpose because they may inhibit two coronaviral enzymes. A drug that can target two viral proteins substantially reduces the ability of the virus to develop resistance. These direct-acting antiviral drugs are also associated with very minimal side effects and are conveniently orally administered.

The aim of this study is to assess the safety and efficacy of the addition of HCV treatment to the standard regimen for the treatment of COVID-19 patients according to MOHP protocol .

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE Drug: Sofosbuvir 400 MG plus Daclatasvir 200mg
This group which receive sofosbuvir and daclatasvir for 14 days plus standard therapy
Other Name: Direct antiviarl agents
Study Arms  ICMJE
  • No Intervention: A)standard therapy group
    No intervention COVID- 19 patients who received a standard therapy group according to the ministry of health protocol
  • Active Comparator: B)Standard Therapy group plus Ant-HCV drugs
    Intervention COVID- 19 patients who received a standard therapy group according to the ministry of health protocol plus sofosbuvir 400 mg and Daclatasvir 200mg
    Intervention: Drug: Sofosbuvir 400 MG plus Daclatasvir 200mg
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: August 31, 2020)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 3, 2021
Estimated Primary Completion Date April 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • All cases positive for COVID-19
  • Male and non-pregnant female patients,
  • 18 years of age or older,
  • All moderate and severe caseswith pneuomnia.

Exclusion Criteria:

  • Known allergy or hypersensitivity to the used medications
  • Known severe liver disease
  • Use of medications that are contraindicated with the trial medications and that could not be replaced or stopped during the trial period
  • Pregnancy or breast-feeding or known active HCV infection, because of concerns about the development of resistance
  • History of bone marrow transplant
  • Known G6PD deficiency
  • Chronic hemodialysis or Glomerular Filtration Rate < 20ml/min
  • Psoriasis
  • Porphyria
  • Concomitant use of digitalis, flecainide, amiodarone, procainamide, or propafenone
  • Known history of long QT syndrome
  • Current known QTc>500 msec
  • Pregnant or nursing
  • Weight < 35kg
  • Seizure disorder
  • Patients receiving Amiodarone.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Egypt
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04535869
Other Study ID Numbers  ICMJE MS.20.08.1214
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Mahmoud Elbendary, Mansoura University
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Mansoura University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Mansoura University
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP