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

• Sponsor: Rajan Saggar (Other)
• Overall Status: Completed
• CT.gov ID: NCT00705133
• Collaborator: United Therapeutics (Industry)
• Enrollment: 15
• Location: 1
• Arm: 1
• Actual Duration (Months): 33
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Arterial Hypertension; Interstitial Lung Disease; Idiopathic Pulmonary Fibrosis	Drug: Treprostinil	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Using Either Intravenous (IV) or Subcutaneous (SQ) Treprostinil to Treat Pulmonary Hypertension Related to Underlying Interstitial Lung Disease
• Actual Study Start Date: Jul 1, 2008
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 6 Minute Walk Distance [3 months]

   American Thoracic Society (ATS) Practice Guideline based 6-minute walk (6MW) distance

Secondary Outcome Measures

1. Pulmonary Vascular Resistance [3 months]

   repeat right heart catheterization

2. SF-36 Quality of Life [3 months]

   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. Brain Natriuretic Peptide [3 months]

   brain natriuretic peptide (BNP) is a measure of right ventricular distension and/or stress due to pressure or volume overload

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	David Geffen School of Medicine, UCLA	Los Angeles	California	United States	90095

Sponsors and Collaborators

• Rajan Saggar
• 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Rajan Saggar, Principal Investigator, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT00705133
• Other Study ID Numbers: 07-11-087-01
• First Posted: Jun 25, 2008
• Last Update Posted: Sep 9, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Rajan Saggar, Principal Investigator, University of California, Los Angeles: pulmonary hypertension; pulmonary fibrosis; interstitial lung disease
• Additional relevant MeSH terms: Lung Diseases; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial; Hypertension; Fibrosis; Treprostinil

Study Results

Participant Flow

Arm/Group Title	Treprostinil-treated
Arm/Group Description	Patients with pulmonary fibrosis with an advanced pulmonary hypertension phenotype will be treated with parenteral treprostinil in an open-label fashion Treprostinil: For both subcutaneous (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
Period Title: Overall Study
STARTED	15
COMPLETED	15
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treprostinil-treated
Arm/Group Description	Patients with pulmonary fibrosis with an advanced pulmonary hypertension phenotype will be treated with parenteral treprostinil in an open-label fashion 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
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 26.7%
>=65 years	11 73.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63 (15)
Sex: Female, Male (Count of Participants)
Female	3 20%
Male	12 80%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 13.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	4 26.7%
More than one race	0 0%
Unknown or Not Reported	9 60%
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treprostinil-treated
Arm/Group Description	Patients with pulmonary fibrosis with an advanced pulmonary hypertension phenotype will be treated with parenteral treprostinil in an open-label fashion 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
Measure Participants	15
Mean (Standard Deviation) [meters]	230 (114)

2. Secondary Outcome

Title	Pulmonary Vascular Resistance
Description	repeat right heart catheterization
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treprostinil-treated
Arm/Group Description	Patients with pulmonary fibrosis with an advanced pulmonary hypertension phenotype will be treated with parenteral treprostinil in an open-label fashion 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
Measure Participants	15
Mean (Standard Deviation) [wood units]	496 (229)

3. Secondary Outcome

Title	SF-36 Quality of Life
Description	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").
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treprostinil-treated
Arm/Group Description	Patients with pulmonary fibrosis with an advanced pulmonary hypertension phenotype will be treated with parenteral treprostinil in an open-label fashion 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
Measure Participants	15
Mean (Standard Deviation) [score on a scale]	28 (8.8)

4. Secondary Outcome

Title	Brain Natriuretic Peptide
Description	brain natriuretic peptide (BNP) is a measure of right ventricular distension and/or stress due to pressure or volume overload
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treprostinil-treated
Arm/Group Description	Patients with pulmonary fibrosis with an advanced pulmonary hypertension phenotype will be treated with parenteral treprostinil in an open-label fashion 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
Measure Participants	15
Mean (Standard Deviation) [pg/mL]	228 (340)

Adverse Events

Arm/Group Title	Treprostinil-treated
Arm/Group Description	Patients with pulmonary fibrosis with an advanced pulmonary hypertension phenotype will be treated with parenteral treprostinil in an open-label fashion 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
All Cause Mortality
	Treprostinil-treated
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treprostinil-treated
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Other (Not Including Serious) Adverse Events
	Treprostinil-treated
	Affected / at Risk (%)	# Events
Total	15/15 (100%)
Gastrointestinal disorders
general prostacyclin adverse reaction profile	15/15 (100%)	15

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.