Pulmonary Arterial Hypertension, Interstitial Lung Disease, Idiopathic Pulmonary Fibrosis
Conditions
Keywords
pulmonary hypertension, pulmonary fibrosis, interstitial lung disease
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.
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.
Interventions
DRUGTreprostinil
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
Sponsors
United Therapeutics
Rajan Saggar
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6 Minute Walk Distance | 3 months | American Thoracic Society (ATS) Practice Guideline based 6-minute walk (6MW) distance |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pulmonary Vascular Resistance | 3 months | repeat right heart catheterization |
| 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). |
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treprostinil-treated 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 | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Treprostinil-treated |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 63 years STANDARD_DEVIATION 15 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
6 Minute Walk Distance
American Thoracic Society (ATS) Practice Guideline based 6-minute walk (6MW) distance
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treprostinil-treated | 6 Minute Walk Distance | 230 meters | Standard Deviation 114 |
Secondary
Brain Natriuretic Peptide
brain natriuretic peptide (BNP) is a measure of right ventricular distension and/or stress due to pressure or volume overload
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treprostinil-treated | Brain Natriuretic Peptide | 228 pg/mL | Standard Deviation 340 |
Secondary
Pulmonary Vascular Resistance
repeat right heart catheterization
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treprostinil-treated | Pulmonary Vascular Resistance | 496 wood units | Standard Deviation 229 |
Secondary
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).
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treprostinil-treated | SF-36 Quality of Life | 28 score on a scale | Standard Deviation 8.8 |