A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis

SIAMS-ED Study Group, T. Colby

Research output: Contribution to journalArticle

349 Citations (Scopus)

Abstract

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.)

Original languageEnglish (US)
Pages (from-to)620-628
Number of pages9
JournalNew England Journal of Medicine
Volume363
Issue number7
DOIs
StatePublished - Aug 12 2010

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Idiopathic Pulmonary Fibrosis
Dyspnea
Placebos
Quality of Life
Carbon Monoxide
National Heart, Lung, and Blood Institute (U.S.)
Phosphodiesterase 5 Inhibitors
Sildenafil Citrate
Randomized Controlled Trials
Gases
Lung

ASJC Scopus subject areas

  • Medicine(all)

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A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. / SIAMS-ED Study Group; Colby, T.

In: New England Journal of Medicine, Vol. 363, No. 7, 12.08.2010, p. 620-628.

Research output: Contribution to journalArticle

SIAMS-ED Study Group ; Colby, T. / A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. In: New England Journal of Medicine. 2010 ; Vol. 363, No. 7. pp. 620-628.
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abstract = "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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T1 - A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis

AU - SIAMS-ED Study Group

AU - Zisman, David A.

AU - Schwarz, Marvin

AU - Anstrom, Kevin J.

AU - Collard, Harold R.

AU - Flaherty, Kevin R.

AU - Hunninghake, Gary W.

AU - de Andrade, J.

AU - Frankel, S.

AU - Kaplan, R.

AU - Lancaster, L.

AU - Raghu, G.

AU - Utz, J. P.

AU - White, S. R.

AU - Zisman, D. A.

AU - Brown, K. K.

AU - de Andrade, J.

AU - Kaner, R. J.

AU - King, T. E.

AU - Lasky, J. A.

AU - Loyd, J. E.

AU - Martinez, F. J.

AU - Raghu, G.

AU - Roman, J.

AU - Ryu, Jay H

AU - Noth, I.

AU - Zisman, D. A.

AU - Chapman, J.

AU - Olman, M.

AU - Lubell, S.

AU - Morrison, L. D.

AU - Steele, M. P.

AU - Haram, T.

AU - Roman, J.

AU - Perez, R.

AU - Perez, T.

AU - Utz, James P

AU - Limper, Andrew Harold

AU - Daniels, C. E.

AU - Meiras, K.

AU - Walsh, S.

AU - Brown, K. K.

AU - Frankel, S.

AU - Kervitsky, D.

AU - Lasky, J. A.

AU - Ditta, S.

AU - de Andrade, J.

AU - Thannickal, V. J.

AU - Stewart, M.

AU - Colby, T.

AU - Lynch, J. P.

PY - 2010/8/12

Y1 - 2010/8/12

N2 - 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.)

AB - 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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DO - 10.1056/NEJMoa1002110

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