RESUMEN

PURPOSE: Ghrelin agonist TZP-101 is a potent prokinetic. This phase 2b study evaluated TZP-101 safety and efficacy in postoperative ileus management. METHODS: Adults undergoing open partial colectomy were adaptively randomized to receive 20, 40, 80, 160, 320, 480 or 600 microg/kg TZP-101 (n = 168) or the placebo (n = 68) by 30-minute IV infusion within 1 hour of surgical closure and then daily for up to 7 days. The primary efficacy end point was the time to first bowel movement. Secondary end points included the percentage of patients with return of gastrointestinal function within 72 hours, and the time to readiness for discharge. RESULTS: TZP-101 accelerated the time to first bowel movement in all groups, with Cox proportional hazard ratios of 1.57 (P = .056) for the low-efficacious dose (80 microg/kg) and 1.67 (P = .03) for the most efficacious dose (480 microg/kg). Using Kaplan-Meier analysis, the median time to first bowel movement was reduced in all TZP-101 groups by 10 to 22 hours vs. the placebo. A greater number of patients who received TZP-101 achieved recovery (P

Asunto(s)

Ghrelina/agonistas , Ileus/tratamiento farmacológico , Compuestos Macrocíclicos/administración & dosificación , Cuidados Posoperatorios/métodos , Proctocolectomía Restauradora/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Ileus/etiología , Infusiones Intravenosas , Compuestos Macrocíclicos/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento