RESUMEN
BACKGROUND: Pulmonary hypertension (PH) accompanying COPD (PH-COPD) is associated with worse outcomes than COPD alone. There are currently no approved therapies to treat PH-COPD. The PERFECT study (ClinicalTrials.gov: NCT03496623) evaluated the safety and efficacy of inhaled treprostinil (iTRE) in this patient population. METHODS: Patients with PH-COPD (mean pulmonary arterial pressure ≥30â mmHg and pulmonary vascular resistance ≥4â WU) were enrolled in a multicentre, randomised (1:1), double-blind, placebo-controlled, 12-week, crossover study. A contingent parallel design was also prespecified and implemented, based on a blinded interim analysis of missing data. Patients received treatment with iTRE up to 12 breaths (72â µg) 4 times daily or placebo. The primary efficacy end-point was change in peak 6-min walk distance (6MWD) at week 12. RESULTS: In total, 76 patients were randomised, 64 in the original crossover design and 12 in the contingent parallel design; 66 patients received iTRE and 58 received placebo. The study was terminated early at the recommendation of the data and safety monitoring committee based on the totality of evidence that iTRE increased the risk of serious adverse events and suggestive evidence of an increased risk of mortality. The change in 6MWD was numerically worse with iTRE exposure than with placebo exposure. CONCLUSIONS: The risk-benefit observations associated with iTRE in patients with PH-COPD did not support continuation of the PERFECT study. The results of this study do not support iTRE as a viable treatment option in patients with PH-COPD.
Asunto(s)
Antihipertensivos , Estudios Cruzados , Epoprostenol , Hipertensión Pulmonar , Enfermedad Pulmonar Obstructiva Crónica , Prueba de Paso , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Epoprostenol/análogos & derivados , Epoprostenol/administración & dosificación , Epoprostenol/uso terapéutico , Femenino , Masculino , Hipertensión Pulmonar/tratamiento farmacológico , Administración por Inhalación , Anciano , Persona de Mediana Edad , Método Doble Ciego , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: There is a need for improved clinical identification of hospitalized patients at risk of aspiration. We evaluated our novel phonetic test in a broad spectrum of patients at risk of aspiration in the ICU or intermediate care unit. METHODS: We prospectively enrolled 60 hospitalized patients with aspiration risk, between December 2009 and September 2011, who subsequently underwent audio-recorded three-component phonetic bedside evaluation. The recordings were scored by two blinded speech-language pathologists. The institutional dysphagia admission screening test was performed by a bedside nurse. The primary outcomes, dysphagia and aspiration, were assessed by a videofluoroscopic swallowing study, fiber-optic endoscopic evaluation of swallowing, or both. We assessed the short- and long-term clinical outcomes (length of stay, subsequent aspiration pneumonia and respiratory failure, survival) and how these were associated with the phonetic and swallow assessments. RESULTS: Statistically significant linear associations with dysphagia were noted for all three individual phonetic components. Also, there were statistically significant linear associations with aspiration for diadochokinesis (P = .050) and consensus auditory-perceptual evaluation of voice (P = .025). Diadochokinesis alone predicted dysphagia (area under the curve [AUC], 0.74; P = .001) and aspiration (AUC, 0.67; P = .012). Its predictive ability improved when combined with normalized dysphagia admission screening test results (AUC, 0.79; P = .001). The short- and long-term clinical outcomes were adversely affected by the worse phonetic/swallowing scores, although they were not statistically different. CONCLUSIONS: Abnormal phonation among ICU and intermediate care unit patients is associated with dysphagia and aspiration. Future investigative efforts should uncover the most effective combination of evaluations for accurate bedside detection of dysphagia and aspiration risk in a broad spectrum of patients.