SARS-CoV Infection, Covid19
Conditions
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.
Interventions
DRUGNitazoxanide
Nitazoxanide (500 mg po BID for day 1and then 500 mg BID for 4 days)
Placebo Nitazoxanide (500 mg po BID for day 1and then 500 mg BID for 4 days)
DRUGRibavirin
Ribavirin (600 mg po BID for day 1and then 400 mg BID for 4 days)
DRUGPlacebo Ribavirin
Placebo Ribavirin (600 mg po BID for day 1and then 400 mg BID for 4 days)
DRUGHydroxychloroquine
Hydroxychloroquine sulfate (400 mg po BID for day 1 and then 200 mg BID for 4 days)
DRUGPlacebo Hydroxychloroquine
Placebo Hydroxychloroquine sulfate (400 mg po BID for day 1 and then 200 mg BID for 4 days)
Sponsors
SynaVir
Rutgers, The State University of New Jersey
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Study medication will be tablets/capsules containing either active drug or placebo
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Decline in Viral Load Over the 10 Days After Randomization | 10 days after randomization | qPCR measured via nasal swab |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Study Drug 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) | 2 |
| Placebo 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) | 5 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Active Study Drug |
|---|---|---|---|
| Age, Continuous | 44 years STANDARD_DEVIATION 15 | 42 years STANDARD_DEVIATION 12.6 | 38 years STANDARD_DEVIATION 2.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 6 Participants | 2 Participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 5 |
| other Total, other adverse events | 0 / 1 | 0 / 5 |
| serious Total, serious adverse events | 0 / 1 | 0 / 5 |
Outcome results
Primary
Rate of Decline in Viral Load Over the 10 Days After Randomization
qPCR measured via nasal swab
Time frame: 10 days after randomization
Population: 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.