920. A Phase 2 Multi-Center, 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
Bibliographic record
Abstract
Abstract Background Norovirus (NoV) results in potentially severe, relapsing, remitting diarrhea in immunocompromised hosts (ICH). A number of interventions, including nitazoxanide (NTZ), have been tried with unclear success in managing cases of NoV in ICH. Methods We conducted a NIH-sponsored multi-center, prospective, randomized, double-blind study of NTZ for the treatment of Norovirus in adult HSCT and SOT recipients between 2018 and 2021. Subjects with a positive Norovirus test within 14 days of enrollment and active GI symptoms were randomly assigned (1:1) to NTZ 500 mg twice daily or placebo (P) for 56 consecutives doses and were followed for 6 months, including patient reported outcomes (PRO) diary assessments. Primary endpoint was to determine the clinical efficacy, assessed as the time from randomization until symptoms resolution for at least 48 hours. Secondary endpoints included virologic efficacy assessed as the time from randomization to first negative viral load and safety through frequency of adverse events. Results 31 subjects (16 NTZ, 15 P) were enrolled and had balanced demographics (See Table 1). Early withdrawal was documented in 5 subjects from each group. Thirty (30) had received solid organ transplants. Most had chronic ( > 14 days) symptoms (77%). In the mITT population, the median time to initial clinical resolution was 19.0 days (95% CI: 1.0, 31.0) for the Nitazoxanide group and 11.0 days (95% CI: 2.0, 14.0) for the placebo group (p-value=0.459). The difference between time to first negative viral load for the Norovirus GII genotype was not significant (p-value=0.873). Patients appear to have clinical improvement based on PRO results while on active therapy. No serious adverse event related to the study treatment was documented. One severe unsolicited adverse event, abdominal pain, was reported on the day of first dose NTZ. Hospitalization and non-serious or laboratory adverse events were not significantly different between the two arms. Analysis of PK and viral genetics is ongoing and will be reported at the meeting. Conclusion NTZ did not shorten time to clinical resolution or viral shedding duration but may have resulted in transient symptom improvement. Although NTZ appears safe, its role is likely limited in the setting of chronic NoV among ICHs. Disclosures Daniel Kaul, MD, Medscape: Honoraria|Nobelpharma: Grant/Research Support|Takeda: Grant/Research Support Robin K. Avery, MD, Aicuris: Grant/Research Support|Astellas: Grant/Research Support|Astra-Zeneca: Grant/Research Support|Chimerix: Grant/Research Support|Merck: Grant/Research Support|Oxford Immunotec: Grant/Research Support|Qiagen: Grant/Research Support|Regeneron: Grant/Research Support|Takeda: Grant/Research Support Ajit Limaye, Professor/MD, MedPace: DSMB member|merck: Advisor/Consultant|merck: Grant/Research Support|moderna: Advisor/Consultant|moderna: site investigator|syneos: DSMB member Steven A. Pergam, MD, MPH, Cidara: Investigator in clinical trials|F2G: Investigator in clinical trials|Global Life Technologies: Grant/Research Support|Symbio: Investigator in clinical trials Michael D. Green, MD, MPH, ADMA: Advisor/Consultant|Allovir: Advisor/Consultant|Bristol Myers Squibb: Advisor/Consultant|ITB-MED: Advisor/Consultant Marian G. Michaels, MD, MPH, Merck: Grant/Research Support|Viracor: Grant/Research Support Lara A. Danziger-Isakov, MD, MPH, Aicuris: Contracted Clinical Research|Ansun Biopharma: Contracted Clinical Research|Astellas: Contracted Clinical Research|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Contracted Clinical Research|Pfizer: Contracted Clinical Research|Roche Diagnostics: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Contracted Clinical Research Michael P. Angarone, DO, Abbvie Pharmeciuticals: Advisor/Consultant|DKBMed Inc: Advisor/Consultant|DKBMed Inc: Honoraria
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".