Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil

Study Overview
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Brief Summary
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Pulmonary Arterial Hypertension (PAH) in the setting of Idiopathic Pulmonary Fibrosis(IPF)is a risk factor for morbidity and mortality in the peri-lung transplant(LT) setting. Currently there is no significant data to support the use of pulmonary vasodilators for PAH in the setting of interstitial lung disease such as IPF. The majority of IPF patients have PAH either at rest or during exercise. The study hypothesis is that sildenafil may improve morbidity and mortality in the peri-LT setting in both IPF cohorts with either resting or exercise PAH.

Detailed Description
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The purpose of this study is to evaluate the use of sildenafil in patients with pulmonary fibrosis and PH being considered for lung transplantation. We hypothesize that not only will sildenafil improve functionality and QOL in the pre-transplant setting but it may also improve primary graft dysfunction after lung transplantation.

Official Title
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Randomized Placebo-Controlled Study of Sildenafil For The Treatment of Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis: A Pilot Study

Conditions
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Pulmonary Arterial Hypertension, Idiopathic Pulmonary Fibrosis, Interstitial Lung Disease, Pulmonary Hypertension

Intervention / Treatment
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* Drug: sildenafil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Idiopathic Pulmonary Fibrosis referred for lung transplantation at our medical center Minimal 6 minute walk distance of 50 meters; must be able to conduct supine exercise during heart catheterization Exclusion Criteria: Non ambulatory Prior adverse reaction/allergy to sildenafil or other PDE-5 Inhibitors Any other pulmonary vasodilator within one month of enrollment
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Pre-transplant placebo<br>There are two placebo comparators.... one for the group of patients with resting PAH and another for the group of patients with exercise PAH | Drug: sildenafil<br>* the dose of sildenafil will be 20mg three times per day (orally)<br>* Other names: Revatio;|
| Experimental: Pre-transplant sildenafil<br>There are two active comparators, one group with resting PAH and another with exercise PAH, both receiving drug. | Drug: sildenafil<br>* the dose of sildenafil will be 20mg three times per day (orally)<br>* Other names: Revatio;|
| No Intervention: Pre-transplant no PAH-specific therapy<br>this group of patients has no evidence for either resting or exercise PAH but will be followed without specific drug intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 minute walk distance (6MWD) change from Baseline | ATS guideline based 6MW distance | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Right heart catheterization hemodynamics | pulmonary hemodynamics via invasive right heart catheterization | initial right heart catheterization compared to catheterization done on day of lung transplantation; we will specifically compare mean pulmonary artery pressure, pulmonary vascular resistance, and pulmonary artery wedge pressure | 
| Chemokine analysis on peripheral blood | evaluation of a group of chemokines before and after the intervention in each arm | the chemokines will be quantified and compared between study entry and the time point just prior to lung transplantation | 
| Quality of life assessment | SF-36 (short-form 36) | study entry compared to 6 months or at the time of lung transplantation (whichever comes first); there is a 0-100 scoring scale and the lower the score, the more disability | 
| Quality of life assessment in the context of dyspnea | Saint George Respiratory Questionnaire (SGRQ) | the SGRQ will be be compared at two time points, study entry and at 6 months or the time of transplantation (whichever comes first); scores range from 0 to 100 and higher scores indicate more limitation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pulmonary hypertension, pulmonary arterial hypertension, interstitial lung disease, idiopathic pulmonary fibrosis