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

A Triple Combination Antiviral Coronavirus Therapy (TriACT) RCT Comparing Nitazoxanide, Ribavirin and Hydroxychloroquine vs. Placebo

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.

Study Overview

• Status: Terminated
• Conditions: Covid19; SARS-CoV Infection
• Intervention / Treatment: Drug: Nitazoxanide; Drug: Ribavirin; Drug: Hydroxychloroquine; Drug: Placebo Nitazoxanide; Drug: Placebo Ribavirin; Drug: Placebo Hydroxychloroquine

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 Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Robert Wood Johnson Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: SynaVir
• Investigators: Principal Investigator: Jeffrey L Carson, MD, Rutgers, the State University of New Jersey

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2020
• Primary Completion (Actual): January 17, 2021
• Study Completion (Actual): February 4, 2021

Study Registration Dates

• First Submitted: October 26, 2020
• First Submitted That Met QC Criteria: October 26, 2020
• First Posted (Actual): October 28, 2020

Study Record Updates

• Last Update Posted (Actual): May 5, 2022
• Last Update Submitted That Met QC Criteria: May 3, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Severe Acute Respiratory Syndrome; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Ribavirin; Hydroxychloroquine; Nitazoxanide
• Other Study ID Numbers: Pro2020001862

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No