Efficacy and Safety of RBX2660 for the Prevention of Recurrent Clostridium difficile Infection: Results. of the PUNCH CD 2 Trial
Notice bibliographique
Résumé
Background. Restoration of the intestinal microbiota is highly efficacious in preventing recurrent Clostridium difficile infection (CDI). RBX2660 is a microbiota-based drug targeted at recurrent CDI. PUNCH CD 2, a multicenter, randomized, placebo-controlled, double-blinded Phase 2b trial was conducted to evaluate the safety and efficacy of RBX2660, including questions about dosing strategy and enema administration. Methods. Patients were randomized to receive: 2 doses of RBX2660 (Group A); 2 doses of placebo (Group B); or 1 dose of RBX2660 and 1 dose of placebo (Group C) via enema with doses 7 days apart. The primary end point was treatment success following 2 doses of RBX2660 compared with 2 doses of placebo. Success was defined as the absence of Clostridium difficile–associated diarrhea at 56 days following completion of the assigned treatment. Failures could receive up to 2 doses of open-label active treatment, 7 days apart. Secondary end points included overall efficacy and safety. Safety was assessed via a patient diary and clinical assessment. Results. A total of 150 patients at 21 sites in the United States and Canada were enrolled in the study. Of these, 127 patients (Group A: n = 41; Group B: n = 44; Group C: n = 42) were in the intention-to-treat population (mean age 61 years; 62.2% female). Efficacy for Group A was 61% versus 45.5% for Group B, P = 0.152. Efficacy for Group C was 66.7% compared with Group B (45.5%), P = 0.048. Efficacy for Group A and C (63.9%) versus B (45.5%), P = 0.046. For patients who developed recurrent CDI after receipt of the study drug, open-label treatment success was: Group A (68.8%, 11/16); Group B (87.5%, 21/24); Group C (71.4%; 10/14) for an overall open-label success rate of 77.8%. The combined efficacy for all patients who received at least 1 active treatment, including those who received open label RBX2660 after initial treatment failure, was 88.8% (n = 95). Adverse events (AEs) at 56 days were primarily gastrointestinal; there were no unanticipated AEs. There was no significant difference in the proportion of adverse or serious AEs among the treatment groups. Conclusion. In patients with recurrent CDI, a single dose of RBX2660 was superior to placebo, and showed equivalent efficacy as 2 doses. RBX2660 administered via enema was safe. Disclosures. E. R. Dubberke, Rebiotix Inc.: Scientific Advisor, Consulting fee and Research support Merck: Consultant and Investigator, Consulting fee and Research grant Sanofi Pasteur: Consultant and Grant Investigator, Consulting fee and Grant recipient Summitt: Consultant, Consulting fee C. Lee, Rebiotix Inc.: Investigator and Scientific Advisor, Consulting fee and Research support R. Orenstein, Rebiotix Inc.: Investigator and Scientific Advisor, Consulting fee and Research support S. Khanna, Rebiotix Inc.: Investigator and Scientific Advisor, Consulting fee and Research support G. Hecht, Rebiotix Inc.: Investigator and Scientific Advisor, Consulting fee and Research support J. Fraiz, Rebiotix Inc.: Investigator, Research support
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 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 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 ».