Trial document




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  DRKS00022203

Trial Description

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Title

Efficacy & Safety of Sofosbuvir/Daclatasvir treatment in COVID-19: A randomized, controlled study

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

This study aims to evaluate the efficacy and safety of Sofosbuvir/Daclatasvir versus Hydroxychloroquine (both with the standard care) in patients with 2019-nCoV infection, initially hospitalized to a non-intensive care setting.
It is a parallel 3-groups, randomized, open-label, active-controlled clinical study.
Ninety patients sufferring from mild up to severe COVID-19 infection will be randomly divided into 3 groups; all will be treated with the standard of care therapy plus an add-on treatment.
The Add-on treatment in the first group will be sofosbuvir plus daclatasvir one tablet for each for 10 days duartion. The second group will have hydroxychloroquine as add-on therapy, while the third group will have only the standard of care therapy. The treatment is planned to be escalated according to the disease progression to admission to intensive care unit or mechanical ventilation for any patient from any group in response to his condition. The three groups will be compared for proportions of patients with clinical recovery at day 14 and 21; time to clinical recovery, time to viral negativity in the nose and throat swab; proportions with adverse reactions to therapy and proportion of those who needed mechanical ventilation.

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Brief Summary in Scientific Language

This study aims to evaluate the efficacy and safety of Sofosbuvir/Daclatasvir versus Hydroxychloroquine (both with the standard care) in patients with 2019-nCoV infection, initially hospitalized to a non-intensive care setting.
It is a parallel 3-groups, randomized, open-label, active-controlled clinical study.
Ninety patients sufferring from mild up to severe COVID-19 infection will be randomly divided into 3 groups; all will be treated with the standard of care therapy plus an add-on treatment.
The Add-on treatment in the first group will be sofosbuvir plus daclatasvir one tablet for each for 10 days duartion. The second group will have hydroxychloroquine as add-on therapy, while the third group will have only the standard of care therapy. The treatment is planned to be escalated according to the disease progression to admission to intensive care unit or mechanical ventilation for any patient from any group in response to his condition. The three groups will be compared for proportions of patients with clinical recovery at day 14 and 21; time to clinical recovery, time to viral negativity in the nasopharyngeal swab; proportions with adverse reactions to therapy and proportion of those who needed mechanical ventilation.

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Do you plan to share individual participant data with other researchers?

No

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00022203
  •   2020/06/15
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  •   no
  •   Approved
  •   IRB0000687, Research Ethics Committee, Egypt Ministry of Health and Population
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Secondary IDs

  •   U1111-1253-0458 
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Health Condition or Problem studied

  •   COVID-19
  •   SARS-nCoV-2 infection
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Interventions/Observational Groups

  •   ARM 1 (Experimental): will receive continued standard of care therapy (as per the MOH protocol) together with a daily dose of one Gratisovir (Sofosbuvir) 400 mg tablet combined with one Daktavera (Daclatasvir) 60 mg table, on Day 1 through day 10.
  •   ARM 2 (Active Comparator): will receive continued standard of care therapy (as the MOH protocol) together with a dose of 4 tablets of Plaquenil (Hydroxychloroquine) 200 mg, on Day 1 followed by 2 tablets daily from day 2 through 5.
  •   ARM 3 (No Intervention Control): will receive continued standard of care therapy (as per the MOH protocol without Hydroxychloroquine or the direct acting antiviral therapy).
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   II-III
  •   Yes
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Primary Outcome

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 (using Exact test with Boot-Strapping).

2. Time to clinical recovery (composite) [Time frame: 21 days after randomization (using Kaplan Meier curve and Cox-regression).

3. Time to viral negativity assessed twice 48 hours apart (log10 viral load assessed by reverse transcription-PCR) during hospital stay (Kaplan Meier curve and Cox-regression).

4. Mean change in Clinical status using 8 point ordinal scale [Day 3 through Day 14, 21 (using Repeated measure Factorial ANOVA test]: 1) Death; 2) Hospitalized, on invasive ventilation or ECMO; 3) Hospitalized, on NIV or HFO2; 4) Hospitalized with oxygen supplement; 5) Hospitalized, not requiring oxygen but need medical care; 6) Hospitalized, not requiring supplemental oxygen or ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized with normal activity.

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Secondary Outcome

1. Proportion of patients who needed the use of mechanical ventilation during hospital stay [Time Frame: 21 days] (using Exact test with Boot-Strapping).
2. Proportions of Participants with Treatment Emergent Serious Adverse Events Leading to Study Drug Discontinuation (using Exact test with Boot-Strapping).

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Countries of Recruitment

  •   Egypt
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Locations of Recruitment

  • Medical Center 
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Recruitment

  •   Actual
  •   2020/06/20
  •   90
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   75   Years
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Additional Inclusion Criteria

(1) Subjects or their legal representatives have signed the informed consent form (ICF).
(2) Subjects are aged ≥ 18 and ≤ 75;
(3) Has 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.

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Exclusion Criteria

(1) Patients with pneumonia due to other etiology.
(2) Critically severe COVID19 ARDS cases Requiring invasive mechanical ventilation at screening;
(3) 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.
(4) Pregnant or lactating females.
(5) Hypersensitivity or contraindication to any of the experimental drugs used in the study (Prolonged QT syndrome, G6PD deficiency, psoriasis, retinal damage or others). .
(6) Patients with decompensated liver cirrhosis or abnormal liver enzyme tests above three times the upper limit values (alanine aminotransferase (ALT) and aspartate aminotransferase (AST);
(7) Renal dysfunction (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73m2);

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Addresses

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    • PHARCO CORPORATE
    • Mr.  Researcher  Sherine  Helmy 
    • Amriya, Alexandria, Egypt
    • 21121  Alexandria
    • Egypt
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    • GREEN CRC
    • Mr.  Clinical research consultant  Mostafa  Yakoot 
    • Green Clinic and Research Centre, Alexandria 21121, Egypt
    • 21121  Alexandria
    • Egypt
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    • GREEN CRC
    • Mr.  Clinical research consultant  Mostafa  Yakoot 
    • Green Clinic and Research Centre, Alexandria 21121, Egypt
    • 21121  Alexandria
    • Egypt
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Sources of Monetary or Material Support

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    • Pharco Corporate
    • Mr.  Researcher  Pharco  Corporate 
    • Amriya, Alexandria, Egypt
    • 21121  Alexandria
    • Egypt
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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