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
Notice bibliographique
Résumé
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
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».