In all patients, the best baseline 6MWD was recorded as the pretreatment value. agent for use in patients with IPF and pulmonary hypertension, and should be analyzed in a large, well-controlled trial. strong class=”kwd-title” Keywords: clinical trial, pulmonary fibrosis, pulmonary hypertension, sildenafil, therapeutics Idiopathic pulmonary fibrosis (IPF) is the most common form of chronic, diffuse lung disease and is associated with a particularly poor prognosis.1,2 Recent data have suggested that many patients with IPF have pulmonary arterial hypertension (PAH). Two large studies3,4 of patients undergoing formal evaluation for lung transplantation found that 33 to 50% of patients exhibited PAH at rest, as assessed by right-heart catheterization. The presence of PAH in IPF patients is associated with poor survival.4C6 Sildenafil (Viagra or Revatio; Pfizer; New York, NY), a phosphodiesterase-5 inhibitor, appears to cause clinically significant pulmonary vasodilation in patients with pulmonary fibrosis.7 The long-term effects of sildenafil on functional steps such as 6-min walk test distance (6MWD) have not been studied in patients with IPF and PAH. We tested the hypothesis that treatment with sildenafil would improve 6MWD in patients with IPF and PAH. Materials and Methods All patients were transitioned into this open-label study from a randomized trial of sildenafil at the University Torin 2 or college of California Los Angeles (ClinicalTrials.gov identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT00352482″,”term_id”:”NCT00352482″NCT00352482). Written informed consent was obtained from each patient. Patients had an established diagnosis of IPF, decided according to accepted criteria,8 and evidence of pulmonary hypertension defined by either (1) a mean pulmonary artery (PA) pressure of 25 mm Hg on right-heart catheterization (n = 10), or (2) a PA systolic pressure of 35 mm Hg on echocardiography (n = 4). Patients with contraindications to phosphodiesterase inhibitor therapy were excluded from the study. Patients performed two baseline 6-min walk assessments (6MWTs) according to altered American Thoracic Society requirements9 on the day of screening to control for potential learning effects. Screening was uncoached, and rest periods were allowed. At the end of 6 min, the total distance walked was recorded. As recommended by American Thoracic Society guidelines,9 the test was terminated if the pulse oximetric saturation fell to 80% and the distance walked prior to termination was recorded. In all patients, the best baseline 6MWD was recorded as the pretreatment value. Patients were then treated with open-label sildenafil (dosed between 20 and 50 mg tid, depending on the formulation available) with a follow-up 6MWT planned for 12 weeks. The primary end point was change in 6MWD (in meters) over time. Secondary end points were clinically meaningful response to sildenafil (defined as a 20% improvement in 6MWD) and incidence of adverse events. The mean switch in 6MWD was reported along with a 90% confidence interval based on nonparametric bootstrap estimates.10 All analyses were performed using a statistical software package (SAS, version 9.2; SAS Institute; Cary, NC). Results Fourteen patients were enrolled in the open-label study (Table Torin 2 1). Eleven patients successfully completed both the baseline and follow-up 6MWTs. The median time between initial and follow-up screening was 91 days. Table 1 Clinical Characteristics* thead th align=”left” rowspan=”1″ colspan=”1″ Variables /th th align=”left” rowspan=”1″ colspan=”1″ Values /th /thead Age, yr72 (7); 71 (63, 85)Female gender6 (43)Smoking history10 (71)Duration of symptoms, mo40.4 (30.0); 34.5 (10, 84)Surgical lung biopsy-proven disease6 (43)Right-heart catheterization performed10 (71)Mean PA pressure,? mm Hg30.7 (5.7); 29.5 (29.0, 43.0)FVC?L2.65 (1.18); 2.39 (0.99, 5.31)?% predicted69.6 (18.4); 71.5 (41.0, 100.0)Dlco?mL/min/mm Hg7.39 (3.92); 7.25 (2.90, 17.80)?% predicted32.4 (17.0); 33.0 (13.0, 79.0) Open in a separate window *Values are given as the mean (SD); median (minimum, maximum) or No. (%). Dlco = diffusing capacity of the lung for carbon monoxide. ?Values reported based on the number Rabbit Polyclonal to PPP4R2 of patients who also underwent right-heart catheterization (n = 10). Individual walk data on all 14 patients are offered in Table 2. Nine patients showed improvement in their 6MWD; only two patients showed a decline. The mean improvement in the 6MWD among those Torin 2 completing both walk assessments (n = 11) was 49.0 m (90% confidence interval, 17.5 to 84.0 m). When all 14 patients were dichotomized into groups of responders ( em ie /em , 20% switch in 6MWD) or nonresponders ( em ie /em , 20% switch in 6MWD or was unable to complete the second 6MWT), 57% of patients were classified as responders. There was no switch in the perceived.