Treprostinil Therapy For Patients With Interstitial Lung Disease And Severe Pulmonary Arterial Hypertension

Using Either Intravenous (IV) or Subcutaneous (SQ) Treprostinil to Treat Pulmonary Hypertension Related to Underlying Interstitial Lung Disease

Our hypothesis is that IV or SQ Treprostinil can improve 6 minute walk distance, hemodynamics and quality of life in patients with interstitial lung disease and severe secondary pulmonary arterial hypertension.

Study Overview

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

Detailed Description

Patients with pulmonary hypertension (PH) complicating pulmonary fibrosis are at increased risk of death. There are no therapies proven to be effective in this population, targeting the pulmonary hypertension. The purpose of this study is to evaluate parenteral treprostinil in an open-label fashion in patients with pulmonary fibrosis and an advanced PH phenotype.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Eligible subjects must have IPF and severe pulmonary arterial hypertension (PAH) documented on standard of care right-heart catheterization (RHC) and planned to receive therapy with treprostinil as recommended by the treating physician.

1. All subjects must have high resolution CT scan (HRCT) diagnostic of IPF (performed as part of standard of care evaluation) or if available, biopsy proven histological usual interstitial pneumonia (UIP).
2. Severe pulmonary arterial hypertension defined as a resting mean pulmonary artery pressure (mPAP) > 35 mm Hg; AND pulmonary vascular resistance (PVR) > 3 woods-units; AND pulmonary capillary wedge pressure (PCWP) < 18 mm Hg by right-heart catheterization (RHC) performed as part of standard of care evaluation.
3. All subjects must be planned to receive treprostinil therapy as recommended by their treating physician.

Exclusion Criteria:

1. Acute or chronic impairment other than dyspnea (e.g. angina pectoris, intermittent claudication) limiting the ability to perform standard of care six-minute walk tests (6MWT).
2. Six-minute walk distance (6MWD) < 50 meters at screening or baseline standard of care evaluations
3. Standard of care pulmonary function test (PFT) showing forced expiratory volume in one second (FEV1)/ forced vital capacity (FVC) ratio < 0.65
4. Standard of care pulmonary function test (PFT) showing a residual volume >120% predicted
5. Standard of care high-resolution chest computed tomography (HRCT) showing emphysema extent > 30%
6. Any investigational therapy as part of a clinical trial for any indication with 30 days before screening
7. Change in dose of treatment for IPF - investigational agent (gamma interferon-1b, pirfenidone, etanercept, and any other investigational agent intended to treat IPF), corticosteroids, or cytotoxic agents, within 30 days before screening. That is, subjects can be on any of these agents provided the dose is stable for at least 30 days prior to enrollment.
8. Current treatment for pulmonary hypertension with other prostaglandins (epoprostenol or iloprost)
9. Change in dose of treatment for PAH - (bosentan, sitaxsentan, ambrisentan, tadalafil, sildenafil, vardenafil, calcium channel blockers, nitrates, digitalis), within 30 days before screening. That is, subjects can be on any of these agents provided the dose is stable for at least 30 days prior to enrollment
10. Pulmonary rehabilitation initiated within 30 days of baseline.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treprostinil-treated; Patients with pulmonary fibrosis with an advanced pulmonary hypertension phenotype will be treated with parenteral treprostinil in an open-label fashion	Drug: Treprostinil; For both SQ and IV routes, treprostinil will be started in the hospital at 1ng/kg/min and titrated up by 1ng/kg/min every 1-3 days as tolerated; Other Names: remodulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 Minute Walk Distance	American Thoracic Society (ATS) Practice Guideline based 6-minute walk (6MW) distance	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary Vascular Resistance	repeat right heart catheterization	3 months
SF-36 Quality of Life	SF-36 physical component summary (PCS) which is one component of the SF-36 survey. The health assessment questionnaire Short Form 36 Version 2.0 (SF-36 V2 ) determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the physical component summary score (PCS) of the SF-36. Scores on each item are summed and averaged (range = 0 "worst"-100 "best").	3 months
Brain Natriuretic Peptide	brain natriuretic peptide (BNP) is a measure of right ventricular distension and/or stress due to pressure or volume overload	3 months

Collaborators and Investigators

• Sponsor: Rajan Saggar
• Collaborators: United Therapeutics
• Investigators: Principal Investigator: Rajan Saggar, MD, David Geffen School of Medicine, UCLA; Principal Investigator: David Zisman, MD, David Geffen School of Medicine, UCLA

Publications and helpful links

General Publications

• Saggar R, Khanna D, Vaidya A, Derhovanessian A, Maranian P, Duffy E, Belperio JA, Weigt SS, Dua S, Shapiro SS, Goldin JG, Abtin F, Lynch JP 3rd, Ross DJ, Forfia PR, Saggar R. Changes in right heart haemodynamics and echocardiographic function in an advanced phenotype of pulmonary hypertension and right heart dysfunction associated with pulmonary fibrosis. Thorax. 2014 Feb;69(2):123-9. doi: 10.1136/thoraxjnl-2013-204150.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2008
• Primary Completion (ACTUAL): January 1, 2011
• Study Completion (ACTUAL): April 1, 2011

Study Registration Dates

• First Submitted: June 23, 2008
• First Submitted That Met QC Criteria: June 24, 2008
• First Posted (ESTIMATE): June 25, 2008

Study Record Updates

• Last Update Posted (ACTUAL): September 9, 2020
• Last Update Submitted That Met QC Criteria: September 7, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: interstitial lung disease; pulmonary hypertension; pulmonary fibrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Hypertension, Pulmonary; Fibrosis; Hypertension; Lung Diseases; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Lung Diseases, Interstitial; Antihypertensive Agents; Treprostinil
• Other Study ID Numbers: 07-11-087-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO