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Study of Oral Administration of Ribavirin and Nitazoxamide Versus Placebo in COVID-19 (DuACT)

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ClinicalTrials.gov Identifier: NCT04563208
Recruitment Status : Recruiting
First Posted : September 24, 2020
Last Update Posted : September 16, 2021
Sponsor:
Collaborator:
SynaVir
Information provided by (Responsible Party):
Professor Francois Venter, University of Witwatersrand, South Africa

Tracking Information
First Submitted Date  ICMJE September 21, 2020
First Posted Date  ICMJE September 24, 2020
Last Update Posted Date September 16, 2021
Actual Study Start Date  ICMJE December 9, 2020
Estimated Primary Completion Date February 28, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 21, 2020)
Rate of decline in viral load [ Time Frame: 10 days ]
Rate of decline in viral load over the 10 days after randomization between participants treated with RBV and NTZ for COVID-19 and placebo
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2020)
  • Time to resolution of viral load [ Time Frame: 28 days ]
    Time to resolution of viral load, defined by reduction of virus below LLOQ and maintaining it for 2 days.
  • Comparison of proportion of subjects who are asymptomatic and symptomatic [ Time Frame: 10 days ]
    Comparison of proportion of subjects who are asymptomatic and symptomatic at day 10
  • Rate of decline in viral load [ Time Frame: Days 3 and 6 ]
    To assess the rate of decline in viral load over days 3 and 6 after randomization
  • Change in modified NEWS-2 [ Time Frame: 28 days ]
    Assess change in modified National Early Warning System-2 items on a scale of 0 to 20. HIgher scores meaning greater clinical risk.
  • Proportion of subjects with treatment emergent adverse events [ Time Frame: 28 days ]
    Proportion of subjects with treatment emergent adverse events leading to study drug discontinuation
Original Secondary Outcome Measures  ICMJE
 (submitted: September 21, 2020)
  • Time to resolution of viral load [ Time Frame: 28 days ]
    Time to resolution of viral load, defined by reduction of virus below LLOQ and maintaining it for 2 days.
  • Comparison of proportion of subjects who are asymptomatic and symptomatic [ Time Frame: 10 days ]
    Comparison of proportion of subjects who are asymptomatic and symptomatic at day 10
  • Rate of decline in viral load [ Time Frame: Days 3 and 6 ]
    To assess the rate of decline in viral load over days 3 and 6 after randomization
  • Change in modified NEWS-2 [ Time Frame: 28 days ]
    Assess change in modified NEWS-2 items
  • Proportion of subjects with treatment emergent adverse events [ Time Frame: 28 days ]
    Proportion of subjects with treatment emergent adverse events leading to study drug discontinuation
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Oral Administration of Ribavirin and Nitazoxamide Versus Placebo in COVID-19
Official Title  ICMJE A Randomized, Double-Blind, Study Comparing the Efficacy, Safety, and Tolerability of Oral Administration of Ribavirin (RBV) and Nitazoxamide (NTZ)Versus Placebo in SARS-CoV-2 Virus Infected Participants (DuACT)
Brief Summary This is a single center, randomized, double-blind, 2-arm, parallel-group study of DuACT in participants with clinical symptoms of COVID-19 that have begun within the past 72 hours prior to testing.
Detailed Description

This is a single center, randomized, double-blind, 2-arm, parallel-group study of DuACT in participants with clinical symptoms of COVID-19 that have begun within the past 72 hours prior to testing. A confirmatory diagnosis of COVID-19 via nasopharyngeal swab, with a positive PCR result within 48 hours of testing.

Consented participants who complete screening and meet study eligibility criteria will be randomized in a 1:1 ratio to receive DuACT or Placebo for 5 days.

Study drugs will be administered BID for 5 days with a loading dose on Day 1. Following randomization, participants will complete a symptom questionnaire, record temperature and record oxygen saturation daily for 10 days and at day 28. A thermometer and pulse oximeter will be provided to each patient at the baseline visit (Day 1).

On study days 3, 6 and 10 participants will have a clinic or home visit by a home healthcare provider. At these visits, a mid-turbinate nasal swab will be obtained, confirmation of the patient's clinical symptoms questionnaire will be completed and any adverse events will be assessed.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Masking Description:
Double-blind
Primary Purpose: Treatment
Condition  ICMJE
  • Covid19
  • SARS-CoV Infection
Intervention  ICMJE
  • Drug: Placebo
    Placebo administered on Days 1-5
  • Drug: DuACT
    Day1: RBV 600 mg BID and NTZ 500 mg BID Days 2-5: RBV 400 mg BID and NTZ 500 mg BID
Study Arms  ICMJE
  • Placebo Comparator: Arm A: Placebo
    Placebo administered
    Intervention: Drug: Placebo
  • Active Comparator: Arm B: Ribavirin/Nitazoxanide (RBV/NTZ)
    Ribavirin/Nitazoxanide (RBV/NTZ) administered
    Intervention: Drug: DuACT
Publications * Not Provided

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 9, 2021)
80
Original Estimated Enrollment  ICMJE
 (submitted: September 21, 2020)
40
Estimated Study Completion Date  ICMJE February 28, 2022
Estimated Primary Completion Date February 28, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Signed a current EC approved informed consent form
  2. Male or female participants between 18 and 75 years of age, inclusive diagnosis of SARS-CoV-2 infection, with all of the following, with onset of any within the 72 hours prior to testing:

    1. Presence of fever at time of screening of ≥ 38.0°C (≥ 100.0°F) and/or
    2. Presence of at least one constitutional symptom associated with Covid-19 (e.g. headache, myalgia, malaise, or fatigue, rash, diarrhea, loss or alteration of taste/smell) of any severity, and/or
    3. Presence of at least one respiratory symptom (e.g. cough, chest tightness or sore throat) and/or
  3. Diagnosis of COVID-19 with a positive PCR in the past 48 hours

Exclusion Criteria:

  1. Pregnant or lactating females
  2. Critically ill with presence of one or more of the following signs:

    1. difficulty breathing or shortness of breath
    2. need for admission to a hospital or an intensive care unit,
    3. acute respiratory failure requiring intubation/mechanical ventilation,
    4. signs of shock including hypotension
    5. Oxygen saturation < 92 %
  3. Any clinically significant screening laboratory results that are greater than 5 times the upper limit of normal.
  4. Estimated GFR < 50 mL/min/1.73 m2 (calculated using either Modification of Diet in Renal Disease (MDRD) or Cockcroft Gualt
  5. Known genetic hemoglobinopathy (e.g., thalassemia major or sickle cell anemia) or autoimmune hemolytic anemia
  6. Hemoglobin less than 10 gm/dL or hematocrit < 30 %
  7. Retinal eye disease
  8. Known chronic kidney disease, stage - 5 or receiving dialysis
  9. Inability to tolerate oral medications
  10. Allergy or prior adverse reaction to either ribavirin or nitazoxanide
  11. QTc interval > 450 mSEC for men and women
  12. History of Torsade de Pointes VT or prior cardiac arrest or congenital long QT interval
  13. Current treatment with histamine-2 receptor antagonists (H2 blockers) and/or Protein Pump Inhibitors and throughout the study.
  14. Have been vaccinated against COVID-19
  15. Have participated in a clinical study in the past 30 days
  16. Any physical, mental, or social condition, drug/alcohol use, history of illness or laboratory abnormality that in the investigator's judgment might interfere with study procedures or the ability of the subject to adhere to and complete the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Simiso Sokhela 82 339 2322 ext +27 ssokhela@ezintsha.org
Listed Location Countries  ICMJE South Africa
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04563208
Other Study ID Numbers  ICMJE DUACT-101
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 Not Provided
Responsible Party Professor Francois Venter, University of Witwatersrand, South Africa
Study Sponsor  ICMJE University of Witwatersrand, South Africa
Collaborators  ICMJE SynaVir
Investigators  ICMJE
Principal Investigator: Simiso Sokhela Ezintsha
PRS Account University of Witwatersrand, South Africa
Verification Date September 2021

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