A Controlled Trial of Sildenafil in Advanced Idiopathic Pulmonary Fibrosis
Open accessAbstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.)
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Bosentan, macitentan, ambrisentan, and sildenafil all failed to improve physiological or symptomatic measures compared with placebo in IPF.
“Bosentan [64,65], macitentan [66], ambrisentan [67] and sildenafil [63,68] all failed to demonstrate improved physiological or symptomatic measures compared to placebo.”
From Emerging pharmacological options in the treatment of idiopathic pulmonary fibrosis (IPF) (2024) · cites this paper as [64]
For sildenafil, the Results and Discussion report no significant benefit on the primary 6-minute-walk outcome, but they report significant improvements versus placebo in physiological measures, dyspnea, and quality of life. Thus the claim that sildenafil failed to improve physiological or symptomatic measures contradicts this paper. This citation is attached to sildenafil, not the other three drugs. (LLM, conf=0.91)
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- Authors
- The Idiopathic Pulmonary Fibrosis Clinical Research Network
- Corresponding author
- The Idiopathic Pulmonary Fibrosis Clinical Research Network
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2010-08-12
- Volume
- 363
- Issue
- 7
- Pages
- 620-628
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC3587293
- OpenAlex
- W2108280422
- Cited by
- 634
- References
- 14
- Citations by year
- 2026: 16 · 2025: 33 · 2024: 32 · 2023: 41 · 2022: 35 · 2021: 38 · 2020: 33 · 2019: 30 · 2018: 46 · 2017: 61 · 2016: 44 · 2015: 50 · 2014: 38 · 2013: 49 · 2012: 39
- FWCI
- 36.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (U10HL80413, U10HL080509, U10HL080543, U10HL80383, U10HL80509, U10HL080571, U10HL80274, U10HL80371, U10HL080383, U10HL080513, U10HL80513, U10HL080685, U10HL80411, U10HL080510, U10HL080413, U10HL80370, U10HL080370, U10HL080411, U10HL80571, U10HL80685, R01HL067967, U10HL80543, U10HL80510, U10HL080274, U10HL080371)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Keywords
- sildenafil, idiopathic pulmonary fibrosis, phosphodiesterase-5 inhibitors, 6-minute walk distance, dyspnea, quality of life, arterial oxygenation, diffusing capacity for carbon monoxide, pulmonary blood flow, gas exchange
- MeSH terms
- Sildenafil Citrate, Administration, Oral, Aged, Double-Blind Method, Dyspnea, Exercise Test, Female, Humans, Male, Middle Aged, Oxygen, Piperazines, Pulmonary Diffusing Capacity, Purines, Quality of Life, Respiratory Function Tests, Sulfones, Vasodilator Agents, Treatment Outcome, Idiopathic Pulmonary Fibrosis
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