A phase 2 multicenter, prospective, randomized, double-blind study to assess the clinical and antiviral efficacy and safety of nitazoxanide for the treatment of norovirus in hematopoietic stem cell and solid organ transplant recipients.

Norovirus (NoV) may cause or contribute to chronic diarrhea among immunocompromised hosts. Neither vaccines nor antiviral therapies are available to prevent or treat NoV infection. We conducted a National Institute of Health-sponsored multicenter, prospective, randomized, double-blind study of nitazoxanide (NTZ) for the treatment of NoV-infected adult transplant patients between 2018 and 2021. Subjects with a positive stool NoV polymerase chain reaction within 14 days of enrollment and active gastrointestinal symptoms were randomly assigned (1:1) to NTZ or placebo (P) for 56 consecutive doses and followed for 6 months. The primary endpoint was time to symptom resolution. Secondary endpoints included virologic efficacy and frequency of adverse events. A total of 31 subjects (16 NTZ and 15 P) were enrolled. Most had chronic (≥14 days) symptoms (77%) and were solid organ transplant recipients (30/31). In the intention-to-treat population, the median time to symptom resolution was 19.0 (95% confidence interval, 1.0-31.0) days vs 11.0 (95% confidence interval, 2.0-14.0) days for the NTZ and P groups, respectively (P = .459). Time to first negative stool NoV polymerase chain reaction was not significantly different between treatment arms (P = .873). There were no serious adverse events related to NTZ. NTZ did not shorten the time to symptom resolution or viral shedding. Although safe, NTZ likely contributes little to the management of chronic NoV. ClinicalTrials.gov: NCT03395405 (registration date 2018-01-04).