Sarcoidosis, Precapillary Pulmonary Hypertension, Interstitial Lung Disease
Conditions
Keywords
right heart catheterization (RHC), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), pulmonary hypertension (PH), Inhaled treprostinil, Sarcoidosis
Brief summary
This study aims to evaluate the efficacy and safety of inhaled treprostinil in subjects with sarcoidosis-associated interstitial lung disease and pulmonary hypertension.
Detailed description
Pulmonary sarcoidosis-associated pulmonary hypertension is classified as WHO Group 5 pulmonary hypertension and may occur in anywhere from 5-20% of sarcoidosis patients. Inhaled treprostinil has shown clinical improvements in exercise capacity after 12 weeks of therapy in patients with WHO Group 1 pulmonary hypertension. More recently, there has been interest in using inhaled PAH-specific therapies for the treatment of pulmonary hypertension associated with interstitial lung disease. The investigators believe that those patients with pulmonary hypertension in the setting of sarcoidosis-associated interstitial lung disease are a unique population which may potentially benefit from inhaled, targeted pulmonary arterial hypertension therapy (inhaled treprostinil) while minimizing the adverse effects associated with systemic pulmonary vasodilators. This study aims to evaluate the efficacy and safety of inhaled treprostinil in subjects with sarcoidosis-associated interstitial lung disease and pulmonary hypertension.
Interventions
Inhaled treprostinil causes dilatation of the pulmonary arteries and may help reduce the pulmonary pressures in this studied population. All subjects will initiate inhaled treprostinil at a dose of 3 breaths (18 mcg) four times daily. Study drug doses escalations (additional one breath four times daily) can occur every three days with a maximum dosing regimen of up to 12 breaths (72 mcg) four times daily, as clinically tolerated.
Sponsors
University of Florida
United Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All subjects will initiate inhaled treprostinil at a dose of 3 breaths (18 mcg) four times daily. Study drug doses escalations (additional one breath four times daily) can occur every three days with a maximum dosing regimen of up to 12 breaths (72 mcg) four times daily, as clinically tolerated.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Study participant willing and able to provide informed consent * Negative urine pregnancy test at baseline for females of childbearing potential * Established diagnosis of sarcoidosis by ATS/ERS/WASOG 1999 Statement on of Sarcoidosis * Presence of interstitial lung disease by Scadding Stage IV chest radiograph or extensive fibrosis on chest computed tomography * Right heart catheterization within six months of baseline visit showing precapillary pulmonary hypertension (mPAP ≥ 25 mmHg, PCWP ≤ 15 mmHg, and PVR \> 3 WU) * Patient on stable sarcoidosis therapy for at least three months prior to screening * If patients are on oral PAH therapy (PDE5i/SCGS and/or ERA) then dose should be stable for at least three months prior to screening * A 6MWT within three months of screening visit of \> 100 meters
Exclusion criteria
* Pregnant patients or those who are actively lactating * Patient not willing to use form of birth control (if applicable) during the study * Inability to undergo 6MWT, RHC, PFTs or CMRI * Predicted survival \< 6 months * Patient on any prostanoid or prostanoid analog therapy * Patients with left sided heart disease as defined by either a PCWP \> 15 mmHg and/or left ventricular ejection fraction \< 40% * Use of any investigational drug/device, or participation in any investigational study with therapeutic intent within 30 days prior to randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PVR by Right heart catheterization (RHC) | Baseline, Week 16 | Change in RHC parameter PVR (pulmonary vascular resistance ) |
| mPAP by Right heart catheterization (RHC) | Baseline, Week 16 | Change in RHC parameter mPAP (mean pulmonary arterial pressure) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in 6-Minute Walk Test (6MWT) | Baseline, Week 8, Week 16 | change in walk test distance during the study |
| Change in Cardiac MRI parameters | Baseline, Week 16 | Change in Right ventricle ejection fraction, Right ventricular end diastolic ventricle index, right ventricular systolic index |
| Change in Pulmonary Function Testing | Baseline, Week 16 | Change in FEV1 abd FVC |
| Change in Brain Natriuretic Peptide (BNP) | Baseline, Week 16 | change in BNP level during the study |
| Change in WHO Functional Class (WHO FC) | Baseline, Week 8, Week 16 | change in WHO FC status during the study |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAli Ataya, MD
University of Florida
Outcome results
None listed