Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Idiopathic Pulmonary Fibrosis; Pulmonary Arterial Hypertension; Pulmonary Hypertension; Interstitial Lung Disease
• Intervention / Treatment: Drug: sildenafil

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-1690
      • David Geffen School of Medicine UCLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Pre-transplant placebo; 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; the dose of sildenafil will be 20mg three times per day (orally); Other Names: Revatio
Experimental: Pre-transplant sildenafil; There are two active comparators, one group with resting PAH and another with exercise PAH, both receiving drug.	Drug: sildenafil; the dose of sildenafil will be 20mg three times per day (orally); Other Names: Revatio
No Intervention: Pre-transplant no PAH-specific therapy; 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?

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

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: Pfizer
• Investigators: Study Director: Rajan Saggar, MD, David Geffen School of Medicine, UCLA

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2007
• Primary Completion (Anticipated): June 1, 2009
• Study Completion (Anticipated): December 1, 2009

Study Registration Dates

• First Submitted: February 19, 2008
• First Submitted That Met QC Criteria: February 19, 2008
• First Posted (Estimate): February 28, 2008

Study Record Updates

• Last Update Posted (Actual): May 1, 2018
• Last Update Submitted That Met QC Criteria: April 27, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: interstitial lung disease; pulmonary hypertension; idiopathic pulmonary fibrosis; pulmonary arterial hypertension
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Fibrosis; Hypertension; Lung Diseases; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Lung Diseases, Interstitial; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: IPF/PH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No