All-cause mortality rate in patients with idiopathic pulmonary fibrosis. Implications for the design and execution of clinical trials
| Autor: | Williamson Z. Bradford, Steven A. Sahn, Paul W. Noble, Talmadge E. King, Steven D. Nathan, Jonathan A. Leff, Dominique Valeyre, du Bois Rm, Ulrich Costabel, Carlo Albera |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Pulmonary and Respiratory Medicine
Adult Male medicine.medical_specialty Pyridones Medizin Kaplan-Meier Estimate Critical Care and Intensive Care Medicine Placebo FEV1/FVC ratio Idiopathic pulmonary fibrosis Interferon-gamma Internal medicine Cause of Death Clinical endpoint medicine Humans Intensive care medicine Cause of death Aged Randomized Controlled Trials as Topic Aged 80 and over Models Statistical business.industry Anti-Inflammatory Agents Non-Steroidal Pirfenidone Middle Aged medicine.disease Idiopathic Pulmonary Fibrosis Recombinant Proteins Clinical trial Treatment Outcome Clinical Trials Phase III as Topic Sample size determination Research Design Sample Size Feasibility Studies Female business medicine.drug Follow-Up Studies |
| Zdroj: | American journal of respiratory and critical care medicine. 189(7) |
| ISSN: | 1535-4970 |
| Popis: | FVC has emerged as a standard primary endpoint in clinical trials evaluating novel therapies for patients with idiopathic pulmonary fibrosis (IPF). However, it has recently been proposed that all-cause mortality or a composite comprised of all-cause mortality and all-cause nonelective hospitalization be adopted as the standard primary endpoint for IPF clinical trials.To conduct a comprehensive evaluation of mortality in three phase 3 clinical trials and evaluate the feasibility of mortality trials in patients with IPF.The study population included 622 patients randomized to placebo in the CAPACITY studies evaluating pirfenidone (n = 347) or the INSPIRE study evaluating interferon-γ1b (n = 275). The Kaplan-Meier estimate of 2-year survival was fit to the exponential distribution and used to calculate sample size requirements for a mortality study with 90% power to detect a 25% reduction in all-cause mortality with a two-sided α of 0.05. Modeling analyses were used to assess the effects of selected variables on sample size and study design.A total of 73 deaths occurred during the period of observation (mean duration of follow-up, 80.1 wk). The all-cause mortality rate was 6.6% at 1 year and 13.7% at 2 years. Based on the observed 2-year mortality rate, a total of 508 events would be required to detect a significant treatment benefit in a two-arm trial with 90% power to detect a 25% reduction in all-cause mortality. The estimated sample size for a trial enrolled over 3 years with a maximum follow-up period of 5 years is 2,582 patients.The all-cause mortality rate is relatively low in patients with IPF with mild to moderate impairment in lung function. Accordingly, the necessary size, duration, and cost of all-cause mortality trials in this population are substantial and likely prohibitive. |
| Databáze: | OpenAIRE |
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