A Controlled Trial of Sildenafil in Advanced Idiopathic Pulmonary Fibrosis
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- 12 August 2010
- journal article
- research article
- Published by Massachusetts Medical Society in The New England Journal of Medicine
- Vol. 363 (7), 620-628
- https://doi.org/10.1056/nejmoa1002110
Abstract
Sildenafil, a phosphodiesterase-5 inhibitor, may preferentially improve blood flow to well-ventilated regions of the lung in patients with advanced idiopathic pulmonary fibrosis, which could result in improvements in gas exchange. We tested the hypothesis that treatment with sildenafil would improve walk distance, dyspnea, and quality of life in patients with advanced idiopathic pulmonary fibrosis, defined as a carbon monoxide diffusion capacity of less than 35% of the predicted value. We conducted a double-blind, randomized, placebo-controlled trial of sildenafil in two periods. The first period consisted of 12 weeks of a double-blind comparison between sildenafil and a placebo control. The primary outcome was the proportion of patients with an increase in the 6-minute walk distance of 20% or more. Key secondary outcomes included changes in oxygenation, degree of dyspnea, and quality of life. The second period was a 12-week open-label evaluation involving all patients receiving sildenafil. A total of 180 patients were enrolled in the study. The difference in the primary outcome was not significant, with 9 of 89 patients (10%) in the sildenafil group and 6 of 91 (7%) in the placebo group having an improvement of 20% or more in the 6-minute walk distance (P=0.39). There were small but significant differences in arterial oxygenation, carbon monoxide diffusion capacity, degree of dyspnea, and quality of life favoring the sildenafil group. Serious adverse events were similar in the two study groups. This study did not show a benefit for sildenafil for the primary outcome. The presence of some positive secondary outcomes creates clinical equipoise for further research. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00517933.)This publication has 13 references indexed in Scilit:
- The SF-36 and SGRQ: Validity and first look at minimum important differences in IPFRespiratory Medicine, 2010
- The 6 minute walk in idiopathic pulmonary fibrosis: longitudinal changes and minimum important differenceThorax, 2009
- Small changes in six-minute walk distance are important in diffuse parenchymal lung diseaseRespiratory Medicine, 2009
- Estimation of minimally important differences in EQ-5D utility and VAS scores in cancerHealth and Quality of Life Outcomes, 2007
- Sildenafil Improves Walk Distance in Idiopathic Pulmonary FibrosisSocial psychiatry. Sozialpsychiatrie. Psychiatrie sociale, 2007
- A potential role for sildenafil in the management of pulmonary hypertension in patients with parenchymal lung diseaseVascular Pharmacology, 2006
- Minimal Clinically Important Difference for the UCSD Shortness of Breath QuestionnaireJournal of Cardiopulmonary Rehabilitation, 2005
- Minimally Clinically Important Difference for the UCSD Shortness of Breath Questionnaire, Borg Scale, and Visual Analog ScaleCOPD: Journal of Chronic Obstructive Pulmonary Disease, 2005
- Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trialThe Lancet, 2002
- Idiopathic Pulmonary Fibrosis: Diagnosis and TreatmentAmerican Journal of Respiratory and Critical Care Medicine, 2000