Clinical trial NCT04605588: A Triple Combination Antiviral Coronavirus Therapy (TriACT) for COVID-19
Official title: A Triple Combination Antiviral Coronavirus Therapy (TriACT) RCT Comparing Nitazoxanide, Ribavirin and Hydroxychloroquine vs. Placebo
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: SARS-CoV Infection
Covid19
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: SynaVir
First posted: 2020-10-28
Enrollment: 7
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of Decline in Viral Load Over the 10 Days After Randomization
timeFrame: 10 days after randomization
Secondary outcomes:
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Robert Wood Johnson Medical School
state: New Jersey
Study officials:
affiliation: Rutgers, The State University of New Jersey
name: Jeffrey L Carson, MD
role: PRINCIPAL_INVESTIGATOR
References: