A Triple Combination Antiviral Coronavirus Therapy (TriACT) for COVID-19

Sponsor
Rutgers, The State University of New Jersey (Other)
Overall Status
Terminated
CT.gov ID
NCT04605588
Collaborator
SynaVir (Other)
7
1
2
2.1
3.3

Study Details

Study Description

Brief Summary

New outpatient treatments for COVID-19 are urgently needed. There is some evidence that a combination of three medications currently used to treat other viral infections could be effective in fighting this new virus. The purpose of this trial is to evaluate the efficacy of Nitazoxanide (NTZ), Ribavirin (RBV) and Hydroxychloroquine (HCQ) versus placebo in participants with proven SARS-CoV-2 infection

The study will enroll 70 participants within the 7 days after having been diagnosed with coronavirus infection. The purpose is to determine if those randomized to 5-day dosing with the three medication combination have decreased viral load and severity of illness in the 10 days following treatment as compared to those taking placebo. Participants will be actively followed for 28 days.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Participants will be randomized into one of two treatment plans

  • Triple combination:

  • Nitazoxanide (500 mg po BID for day 1and then 500 mg BID for 4 days)

  • Ribavirin (600 mg po BID for day 1and then 400 mg BID for 4 days)

  • Hydroxychloroquine sulfate (400 mg po BID for day 1 and then 200 mg BID for 4 days)

  • No active Medication:

  • Placebo administered according to the above schedule

Viral load (qPCR via nasal swab) will be assessed at baseline (day 0) as well as at days 3, 6, and 10 to monitor response to antiviral treatment. Immune status will be determined by antibody testing of blood collected at baseline and day 28. Symptom questionnaires will be completed daily for 10 days and day 28.

Study Design

Study Type:
Interventional
Actual Enrollment :
7 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Study medication will be tablets/capsules containing either active drug or placebo
Primary Purpose:
Treatment
Official Title:
A Triple Combination Antiviral Coronavirus Therapy (TriACT) RCT Comparing Nitazoxanide, Ribavirin and Hydroxychloroquine vs. Placebo
Actual Study Start Date :
Dec 2, 2020
Actual Primary Completion Date :
Jan 17, 2021
Actual Study Completion Date :
Feb 4, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Active Study Drug

5 day dosing of Nitazoxanide, Ribavirin & Hydroxychloroquine sulfate

Drug: Nitazoxanide
Nitazoxanide (500 mg po BID for day 1and then 500 mg BID for 4 days)

Drug: Ribavirin
Ribavirin (600 mg po BID for day 1and then 400 mg BID for 4 days)

Drug: Hydroxychloroquine
Hydroxychloroquine sulfate (400 mg po BID for day 1 and then 200 mg BID for 4 days)

Placebo Comparator: Placebo

5 day dosing of placebo

Drug: Placebo Nitazoxanide
Placebo Nitazoxanide (500 mg po BID for day 1and then 500 mg BID for 4 days)

Drug: Placebo Ribavirin
Placebo Ribavirin (600 mg po BID for day 1and then 400 mg BID for 4 days)

Drug: Placebo Hydroxychloroquine
Placebo Hydroxychloroquine sulfate (400 mg po BID for day 1 and then 200 mg BID for 4 days)

Outcome Measures

Primary Outcome Measures

  1. Rate of Decline in Viral Load Over the 10 Days After Randomization [10 days after randomization]

    qPCR measured via nasal swab

Eligibility Criteria

Criteria

Ages Eligible for Study:
21 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Documented SARS-CoV-2 infection by qPCR assay performed within the past 7 days
Exclusion Criteria:
  • COVID-19 symptoms requiring hospitalization

  • PO2 < 92%

  • Short of breath at time of enrollment

  • Retinal eye disease

  • Known glucose-6 phosphate dehydrogenase (G-6-PD) deficiency

  • Known chronic kidney disease, stage - 5 or receiving dialysis

  • Current use of:

  • Class 3 AAD (amiodarone, dronaderone, dofetilide, sotalol)

  • Class 1A AAD (procainamide, quinidine, disopyramide)

  • Flecainide

  • SSRI: citalopram (Celexa), Escitalopram (Lexapro)

  • chlorpromazine

  • Cilostazol (Pletal)

  • Donepezil (Aricept)

  • Droperidol

  • Fluoconazole

  • Methadone

  • Ondansetron (Zofran)

  • Thioridazine

  • Macrolides (clarithromycin, erythromycin)

  • Fluroquinolones (ciprofloxacin, levofloxacin, moxifloxacin)

  • Tamoxifen

  • Pregnancy or women who are breast feeding

  • Inability to tolerate oral medications

  • Allergy or prior adverse reaction to either hydroxychloroquine sulfate, ribavirin, or nitazoxanide

  • Allergy to adhesives

  • QTc interval > 450 mSEC for men and women

  • History of Torsade de Pointes VT or prior cardiac arrest or congenital long QT interval

  • Non-English-speaking

Contacts and Locations

Locations

Site City State Country Postal Code
1 Robert Wood Johnson Medical School New Brunswick New Jersey United States 08903

Sponsors and Collaborators

  • Rutgers, The State University of New Jersey
  • SynaVir

Investigators

  • Principal Investigator: Jeffrey L Carson, MD, Rutgers, The State University of New Jersey

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Jeffrey L Carson, MD, Distinguished Professor of Medicine, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey
ClinicalTrials.gov Identifier:
NCT04605588
Other Study ID Numbers:
  • Pro2020001862
First Posted:
Oct 28, 2020
Last Update Posted:
May 5, 2022
Last Verified:
May 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Active Study Drug Placebo
Arm/Group Description 5 day dosing of Nitazoxanide, Ribavirin & Hydroxychloroquine sulfate Nitazoxanide: Nitazoxanide (500 mg po BID for day 1and then 500 mg BID for 4 days) Ribavirin: Ribavirin (600 mg po BID for day 1and then 400 mg BID for 4 days) Hydroxychloroquine: Hydroxychloroquine sulfate (400 mg po BID for day 1 and then 200 mg BID for 4 days) 5 day dosing of placebo Placebo Nitazoxanide: Placebo Nitazoxanide (500 mg po BID for day 1and then 500 mg BID for 4 days) Placebo Ribavirin: Placebo Ribavirin (600 mg po BID for day 1and then 400 mg BID for 4 days) Placebo Hydroxychloroquine: Placebo Hydroxychloroquine sulfate (400 mg po BID for day 1 and then 200 mg BID for 4 days)
Period Title: Overall Study
STARTED 2 5
COMPLETED 1 5
NOT COMPLETED 1 0

Baseline Characteristics

Arm/Group Title Active Study Drug Placebo Total
Arm/Group Description 5 day dosing of Nitazoxanide, Ribavirin & Hydroxychloroquine sulfate Nitazoxanide: Nitazoxanide (500 mg po BID for day 1and then 500 mg BID for 4 days) Ribavirin: Ribavirin (600 mg po BID for day 1and then 400 mg BID for 4 days) Hydroxychloroquine: Hydroxychloroquine sulfate (400 mg po BID for day 1 and then 200 mg BID for 4 days) 5 day dosing of placebo Placebo Nitazoxanide: Placebo Nitazoxanide (500 mg po BID for day 1and then 500 mg BID for 4 days) Placebo Ribavirin: Placebo Ribavirin (600 mg po BID for day 1and then 400 mg BID for 4 days) Placebo Hydroxychloroquine: Placebo Hydroxychloroquine sulfate (400 mg po BID for day 1 and then 200 mg BID for 4 days) Total of all reporting groups
Overall Participants 2 5 7
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
38
(2.8)
44
(15.0)
42
(12.6)
Sex: Female, Male (Count of Participants)
Female
2
100%
3
60%
5
71.4%
Male
0
0%
2
40%
2
28.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
0
0%
1
20%
1
14.3%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
0
0%
0
0%
0
0%
White
2
100%
4
80%
6
85.7%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
0
0%
0
0%

Outcome Measures

1. Primary Outcome
Title Rate of Decline in Viral Load Over the 10 Days After Randomization
Description qPCR measured via nasal swab
Time Frame 10 days after randomization

Outcome Measure Data

Analysis Population Description
This trial was terminated due to lack of enrollment. A total of 7 participants were randomized. Study outcome was to be response to antiviral treatment (rate of decline in viral load over the 10 days after randomization) as measured via nasal swab qPCR analysis. Based on the lack of enrollment, the swab analysis was not performed.
Arm/Group Title Active Study Drug Placebo
Arm/Group Description 5 day dosing of Nitazoxanide, Ribavirin & Hydroxychloroquine sulfate Nitazoxanide: Nitazoxanide (500 mg po BID for day 1and then 500 mg BID for 4 days) Ribavirin: Ribavirin (600 mg po BID for day 1and then 400 mg BID for 4 days) Hydroxychloroquine: Hydroxychloroquine sulfate (400 mg po BID for day 1 and then 200 mg BID for 4 days) 5 day dosing of placebo Placebo Nitazoxanide: Placebo Nitazoxanide (500 mg po BID for day 1and then 500 mg BID for 4 days) Placebo Ribavirin: Placebo Ribavirin (600 mg po BID for day 1and then 400 mg BID for 4 days) Placebo Hydroxychloroquine: Placebo Hydroxychloroquine sulfate (400 mg po BID for day 1 and then 200 mg BID for 4 days)
Measure Participants 0 0

Adverse Events

Time Frame 28 Days
Adverse Event Reporting Description
Arm/Group Title Active Study Drug Placebo
Arm/Group Description 5 day dosing of Nitazoxanide, Ribavirin & Hydroxychloroquine sulfate Nitazoxanide: Nitazoxanide (500 mg po BID for day 1and then 500 mg BID for 4 days) Ribavirin: Ribavirin (600 mg po BID for day 1and then 400 mg BID for 4 days) Hydroxychloroquine: Hydroxychloroquine sulfate (400 mg po BID for day 1 and then 200 mg BID for 4 days) 5 day dosing of placebo Placebo Nitazoxanide: Placebo Nitazoxanide (500 mg po BID for day 1and then 500 mg BID for 4 days) Placebo Ribavirin: Placebo Ribavirin (600 mg po BID for day 1and then 400 mg BID for 4 days) Placebo Hydroxychloroquine: Placebo Hydroxychloroquine sulfate (400 mg po BID for day 1 and then 200 mg BID for 4 days)
All Cause Mortality
Active Study Drug Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/1 (0%) 0/5 (0%)
Serious Adverse Events
Active Study Drug Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/1 (0%) 0/5 (0%)
Other (Not Including Serious) Adverse Events
Active Study Drug Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/1 (0%) 0/5 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Jeffrey L Carson, MD
Organization Rutgers, The State University of New Jersey
Phone 732-235-7122
Email Jeffrey.Carson@Rutgers.edu
Responsible Party:
Jeffrey L Carson, MD, Distinguished Professor of Medicine, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey
ClinicalTrials.gov Identifier:
NCT04605588
Other Study ID Numbers:
  • Pro2020001862
First Posted:
Oct 28, 2020
Last Update Posted:
May 5, 2022
Last Verified:
May 1, 2022