SAPPHIRE: Inhaled Treprostinil in Sarcoidosis Patients With Pulmonary Hypertension

Sponsor

University of Florida (Other)

Overall Status

Recruiting

CT.gov ID

NCT03814317

Collaborator

United Therapeutics (Industry)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sarcoidosis Precapillary Pulmonary Hypertension Interstitial Lung Disease	Drug: Inhaled Treprostinil	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-Label Study of Inhaled Treprostinil in Sarcoidosis Patients With Pulmonary Hypertension and Interstitial Lung Disease (SAPPHIRE)

Actual Study Start Date :

Jan 30, 2020

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Study Group Sarcoidosis patients with interstitial lung disease and precapillary pulmonary hypertension based on right heart catheterization (RHC). 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.	Drug: Inhaled Treprostinil 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. Other Names: Tyvaso® pulmonary arterial hypertension (PAH) therapy

Arm

Intervention/Treatment

Experimental: Study Group

Sarcoidosis patients with interstitial lung disease and precapillary pulmonary hypertension based on right heart catheterization (RHC). 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.

Drug: Inhaled Treprostinil

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.

Other Names:

Tyvaso®

pulmonary arterial hypertension (PAH) therapy

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Change in 6-Minute Walk Test (6MWT) [Baseline, Week 8, Week 16]
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 WHO Functional Class (WHO FC) [Baseline, Week 8, Week 16]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.