RESUMEN
The increasing burden and the continued suboptimal outcomes for patients with heart failure underlines the importance of continued research to develop novel therapeutics for this disorder. This can only be accomplished with successful translation of basic science discoveries into direct human application through effective clinical trial design and execution that results in a substantially improved clinical course and outcomes. In this respect, phase II clinical trials play a pivotal role in determining which of the multitude of potential basic science discoveries should move to the large and expansive registration trials in humans. A critical examination of the phase II trials in heart failure reveals multiple shortcomings in their concept, design, execution, and interpretation. To further a dialogue on the challenges and potential for improvement and the role of phase II trials in patients with heart failure, the Food and Drug Administration facilitated a meeting on October 17, 2016, represented by clinicians, researchers, industry members, and regulators. This document summarizes the discussion from this meeting and provides key recommendations for future directions.
Asunto(s)
Fármacos Cardiovasculares/uso terapéutico , Ensayos Clínicos Fase II como Asunto/normas , Insuficiencia Cardíaca/tratamiento farmacológico , Proyectos de Investigación/normas , Fármacos Cardiovasculares/efectos adversos , Ensayos Clínicos Fase II como Asunto/métodos , Consenso , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Humanos , Resultado del Tratamiento , Estados Unidos , United States Food and Drug AdministrationRESUMEN
The epidemiological, clinical, and societal implications of the heart failure (HF) epidemic cannot be overemphasized. Approximately half of all HF patients have HF with preserved ejection fraction (HFpEF). HFpEF is largely a syndrome of the elderly, and with aging of the population, the proportion of patients with HFpEF is expected to grow. Currently, there is no drug known to improve mortality or hospitalization risk for these patients. Besides mortality and hospitalization, it is imperative to realize that patients with HFpEF have significant impairment in their functional capacity and their quality of life on a daily basis, underscoring the need for these parameters to ideally be incorporated within a regulatory pathway for drug approval. Although attempts should continue to explore therapies to reduce the risk of mortality or hospitalization for these patients, efforts should also be directed to improve other patient-centric concerns, such as functional capacity and quality of life. To initiate a dialogue about the compelling need for and the challenges in developing such alternative endpoints for patients with HFpEF, the US Food and Drug Administration on November 12, 2015, facilitated a meeting represented by clinicians, academia, industry, and regulatory agencies. This document summarizes the discussion from this meeting.
Asunto(s)
Insuficiencia Cardíaca/terapia , Hospitalización , Mortalidad , Medición de Resultados Informados por el Paciente , Volumen Sistólico , Congresos como Asunto , Aprobación de Drogas , Descubrimiento de Drogas , Prueba de Esfuerzo , Insuficiencia Cardíaca/fisiopatología , Humanos , Evaluación de Resultado en la Atención de Salud , Consumo de Oxígeno , Calidad de Vida , Estados Unidos , United States Food and Drug Administration , Prueba de PasoRESUMEN
Preemptive analgesia is an important part of surgical management, but some NSAIDs can adversely affect platelet function or renal or hepatic status. Tepoxalin is approved in the United States for control of pain and inflammation associated with arthritis and in Europe for relief of pain caused by musculoskeletal disorders. In this study, no significant effects on indices of hemostasis or renal or hepatic function were detected when a single preoperative oral dose of tepoxalin was administered to young healthy dogs undergoing anesthesia and surgery.
Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Hemostasis/efectos de los fármacos , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Medicación Preanestésica/veterinaria , Pirazoles/administración & dosificación , Analgesia/métodos , Analgesia/veterinaria , Animales , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/farmacología , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/prevención & control , Perros , Femenino , Hemostasis Quirúrgica , Riñón/fisiología , Hígado/fisiología , Masculino , Dolor/tratamiento farmacológico , Dolor/prevención & control , Dolor/veterinaria , Pirazoles/efectos adversos , Pirazoles/farmacología , Distribución Aleatoria , Resultado del TratamientoRESUMEN
Plasma and skin concentrations of orbifloxacin (Orbax tablets, Schering-Plough Animal Health) were assessed in 14 clinically normal dogs and 14 dogs with pyoderma following oral administration of the drug at 7.5 mg/kg once daily for 5 to 7 days. Skin biopsies and whole blood samples were obtained before dosing and at the time of the expected maximum concentration in skin (3 hours after dosing) on the first and on the fifth to seventh day of dosing. Skin biopsies and plasma were analyzed for orbifloxacin concentrations by high-performance liquid chromatography. Dogs with pyoderma had significantly higher mean skin concentrations of orbifloxacin within 3 hours of administration (Day 0: 7.80 +/- 3.40 mcg/g, Days 4 to 6: 9.47 +/- 6.23 mcg/g) than did dogs with normal skin (Day 0: 3.85 +/- 1.08 mcg/g, Days 4 to 6: 5.43 +/- 1.02 mcg/g). After dosing on Day 0 and after five to seven daily treatments, dogs with pyoderma had significantly higher mean orbifloxacin skin:plasma ratios (1.40 and 1.44, respectively) than did clinically normal dogs (0.81 and 0.96, respectively). The accumulation of orbifloxacin in diseased skin may contribute to the efficacy of this compound for the treatment of bacterial skin infections.