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

Primary Purpose

Covid19, SARS-CoV Infection

Status

Completed

Phase

Phase 2

Locations

South Africa

Study Type

Interventional

Intervention

Placebo

DuACT

About this trial

This is an interventional treatment trial for Covid19 focused on measuring Ribavirin, Nitazoxanide, SARS-CoV-2

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Signed a current EC approved informed consent form
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
Diagnosis of COVID-19 with a positive PCR in the past 48 hours

Exclusion Criteria:

Pregnant or lactating females
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 %
Any clinically significant screening laboratory results that are greater than 5 times the upper limit of normal.
Estimated GFR < 50 mL/min/1.73 m2 (calculated using either Modification of Diet in Renal Disease (MDRD) or Cockcroft Gualt
Known genetic hemoglobinopathy (e.g., thalassemia major or sickle cell anemia) or autoimmune hemolytic anemia
Hemoglobin less than 10 gm/dL or hematocrit < 30 %
Retinal eye disease
Known chronic kidney disease, stage - 5 or receiving dialysis
Inability to tolerate oral medications
Allergy or prior adverse reaction to either ribavirin or nitazoxanide
QTc interval > 450 mSEC for men and women
History of Torsade de Pointes VT or prior cardiac arrest or congenital long QT interval
Current treatment with histamine-2 receptor antagonists (H2 blockers) and/or Protein Pump Inhibitors and throughout the study.
Have been vaccinated against COVID-19
Have participated in a clinical study in the past 30 days
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

Sites / Locations

Sunnyside Office Park

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Arm A: Placebo

Arm B: Ribavirin/Nitazoxanide (RBV/NTZ)

Arm Description

Placebo administered

Ribavirin/Nitazoxanide (RBV/NTZ) administered

Outcomes

Primary Outcome Measures

Rate of decline in viral load

Rate of decline in viral load over the 10 days after randomization between participants treated with RBV and NTZ for COVID-19 and placebo

Secondary Outcome Measures

Time to resolution of viral load

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

Comparison of proportion of subjects who are asymptomatic and symptomatic at day 10

Rate of decline in viral load

To assess the rate of decline in viral load over days 3 and 6 after randomization

Change in modified NEWS-2

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

Proportion of subjects with treatment emergent adverse events leading to study drug discontinuation

Full Information

NCT ID

NCT04563208

First Posted

September 21, 2020

Last Updated

July 13, 2022

Sponsor

University of Witwatersrand, South Africa

Collaborators

SynaVir

1. Study Identification

Unique Protocol Identification Number

NCT04563208

Brief Title

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

Acronym

DuACT

Official Title

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)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Completed

Study Start Date

December 9, 2020 (Actual)

Primary Completion Date

February 28, 2022 (Actual)

Study Completion Date

February 28, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Witwatersrand, South Africa

Collaborators

SynaVir

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Covid19, SARS-CoV Infection

Keywords

Ribavirin, Nitazoxanide, SARS-CoV-2

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare Provider

Masking Description

Double-blind

Allocation

Randomized

Enrollment

80 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A: Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo administered

Arm Title

Arm B: Ribavirin/Nitazoxanide (RBV/NTZ)

Arm Type

Active Comparator

Arm Description

Ribavirin/Nitazoxanide (RBV/NTZ) administered

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo administered on Days 1-5

Intervention Type

Drug

Intervention Name(s)

DuACT

Intervention Description

Day1: RBV 600 mg BID and NTZ 500 mg BID Days 2-5: RBV 400 mg BID and NTZ 500 mg BID

Primary Outcome Measure Information:

Title

Rate of decline in viral load

Description

Rate of decline in viral load over the 10 days after randomization between participants treated with RBV and NTZ for COVID-19 and placebo

Time Frame

10 days

Secondary Outcome Measure Information:

Title

Time to resolution of viral load

Description

Time to resolution of viral load, defined by reduction of virus below LLOQ and maintaining it for 2 days.

Time Frame

28 days

Title

Comparison of proportion of subjects who are asymptomatic and symptomatic

Description

Comparison of proportion of subjects who are asymptomatic and symptomatic at day 10

Time Frame

10 days

Title

Rate of decline in viral load

Description

To assess the rate of decline in viral load over days 3 and 6 after randomization

Time Frame

Days 3 and 6

Title

Change in modified NEWS-2

Description

Assess change in modified National Early Warning System-2 items on a scale of 0 to 20. HIgher scores meaning greater clinical risk.

Time Frame

28 days

Title

Proportion of subjects with treatment emergent adverse events

Description

Proportion of subjects with treatment emergent adverse events leading to study drug discontinuation

Time Frame

28 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Signed a current EC approved informed consent form 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: Presence of fever at time of screening of ≥ 38.0°C (≥ 100.0°F) and/or 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 Presence of at least one respiratory symptom (e.g. cough, chest tightness or sore throat) and/or Diagnosis of COVID-19 with a positive PCR in the past 48 hours Exclusion Criteria: Pregnant or lactating females Critically ill with presence of one or more of the following signs: difficulty breathing or shortness of breath need for admission to a hospital or an intensive care unit, acute respiratory failure requiring intubation/mechanical ventilation, signs of shock including hypotension Oxygen saturation < 92 % Any clinically significant screening laboratory results that are greater than 5 times the upper limit of normal. Estimated GFR < 50 mL/min/1.73 m2 (calculated using either Modification of Diet in Renal Disease (MDRD) or Cockcroft Gualt Known genetic hemoglobinopathy (e.g., thalassemia major or sickle cell anemia) or autoimmune hemolytic anemia Hemoglobin less than 10 gm/dL or hematocrit < 30 % Retinal eye disease Known chronic kidney disease, stage - 5 or receiving dialysis Inability to tolerate oral medications Allergy or prior adverse reaction to either ribavirin or nitazoxanide QTc interval > 450 mSEC for men and women History of Torsade de Pointes VT or prior cardiac arrest or congenital long QT interval Current treatment with histamine-2 receptor antagonists (H2 blockers) and/or Protein Pump Inhibitors and throughout the study. Have been vaccinated against COVID-19 Have participated in a clinical study in the past 30 days 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Simiso Sokhela

Organizational Affiliation

Ezintsha

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sunnyside Office Park

City

Johannesburg

State/Province

Gauteng

Country

South Africa

12. IPD Sharing Statement

Learn more about this trial

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

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