Trial NCT04486313
Publication Rossignol JF, EClinicalMedicine (2022) (published paper)
Dates: 2020-08-18 to 2021-01-08
Funding: Private (Romark Institute of Medical Research)
Conflict of interest: Yes

Methods
RCT
Blinding: double blinding
Location : Multicenter / Puerto Rico, USA
Follow-up duration (days): 28
Inclusion criteria
  • At least 12 years of age presenting within 72 hours of onset of symptoms of mild or moderate COVID-19
  • Minimum symptom requirements were: At least two respiratory symptom domains (head, throat, nose, chest, cough) with a score of ≥2 as determined by scoring the InFLUenza Patient-Reported Outcomes (FLU-PRO©) questionnaire administered at screening (only one domain score required to be ≥2 if pulse rate ≥90 beats per minute or respiratory rate ≥16 breaths per minute)
  • no improvement in overall symptom severity from the prior day.
Exclusion criteria
  • Signs or symptoms suggestive of severe COVID-19 including shortness of breath at rest, resting pulse rate ≥125 beats per minute, resting respiratory rate ≥30 breaths per minute, or SpO2 ≤ 93% on room air at sea level
  • previous COVID-19 infection or any symptom suggestive of COVID-19
  • recent episodes (two weeks) of acute upper respiratory tract infection, otitis, bronchitis or sinusitis
  • immunodeficiency, such as in subjects undergoing chemotherapy, transplant recipients receiving immunosuppressive therapy, and HIV patients with a CD4 count below 350 cells/mm3 in the last six months
  • females of childbearing potential who were either pregnant or sexually active and not using birth control.
Interventions
Treatment
Nitazoxanide
600 mg orally twice a day for 5 days
Control
Placebo

Participants
Randomized
NR

Analyzed
379 participants Nitazoxanide =184
Placebo=195
Characteristics of participants
N= 379
Mean age : NR
165 males
Severity : Mild: n= 379/ Asymptomatic: n=0
Number of vaccinated participants: 0
Primary outcome
In the register
Reducing the Time to Sustained Response [ Time Frame: Up to 21 days ]
In the report
Time from the first dose to sustained response (TSR), a measure of meaningful within-subject change in symptoms
Documents
available

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

N
Risk of bias
Overall
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
Some concerns
General comment In addition to the all versions of the published and pre-print articles (SSRN and medRxiv), the prospective trial registry was used in data extraction and assessment of risk of bias. Neither study protocol nor statistical analysis plan was available. There is no change from the trial registration in the intervention and control treatments. The registry primary outcome reflects the reported primary outcome. Several outcomes reported in the article were not included in the trial registry. When all participants randomized or included for safety are considered, the study achieved its original target sample size.
Of note, participants were recruited, randomized and tested at first clinic visit with suspected COVID-19. Many were subsequently excluded from efficacy analysis for a number of reasons:
a) Of 1,092 randomized, 156 subjects positive for rhinovirus/enterovirus and negative for SARS-CoV-2 at baseline were not included in ANY analysis as they are to be analyzed later as part of a separate study targeting enterovirus/ rhinovirus infection.
b) 1 participant withdrew consent prior to receiving treatment, but not reported which arm.
All remaining participants (n=935) who received treatment were included in the safety analysis after receiving intervention or placebo. (All outcomes extracted were in this population: mortality, AE, SAE).
This study study was updated on March 9th, 2022 with data from the new versions of the preprints.
This study was updated on April 27th, 2022 with data extracted from the peer-reviewed article.