Tadalafil for Sarcoidosis Associated Pulmonary Hypertension

Phase 2

Completed

• Conditions: Pulmonary Hypertension
• Interventions: Drug: Tadalafil

• Registration Number: NCT01324999
• Lead Sponsor: University of North Carolina, Chapel Hill

Brief Summary

This study is designed to assess safety and efficacy of tadalafil in patients with Sarcoidosis Associated Pulmonary Hypertension.

Hypothesis: Tadalafil is safe and effective in treating pulmonary hypertension in patients with Sarcoidosis

Detailed Description

Not available

Study Timeline

• Study Start: 2011-03
• Study First Submitted: 2011-03-24
• Study First Submitted QC: 2011-03-28
• Study First Posted: 2011-03-29
• Primary Completion: 2013-07
• Study Completion: 2013-10
• Results First Submitted: 2017-03-21
• Status Verified: 2017-06
• Results First Submitted QC: 2017-06-25
• Last Update Submitted: 2017-06-25
• Results First Posted: 2017-07-24
• Last Update Posted: 2017-07-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Biopsy proven sarcoidosis
• Mean pulmonary artery pressure > 25 mmHg at rest or greater than 30 mmHg with exercise by right heart catheterization within 1 year prior to entry into study
• Pulmonary capillary wedge pressure ≤ 15 mmHg
• PVR values ≥ 3.0 Woods units
• Forced vital capacity (FVC) > 40% predicted
• Forced expiratory volume in 1 second (FEV1) > 40% predicted
• WHO functional class II or III
• Stable sarcoidosis treatment regimen for three months prior to entry into study
• 6 minute walk distance between 150-450 meters
• Stable dose of antihypertensive medications
• On no other medication to treat PAH (sildenafil, vardenafil, treprostinil, epoprostenol, iloprost, bosentan, ambrisentan) within one month prior to enrollment and during duration of the study
• Non-pregnant females

Exclusion Criteria

• Exercise limitation related to a non-cardiopulmonary reason (e.g. arthritis)
• Severe systemic hypertension > 170/95
• Severe systemic hypotension < 90/50
• History of priapism
• Patients with congestive heart failure (left ventricular dysfunction) LVEF < 45% by echocardiogram
• Anticipation by the investigator for escalation in sarcoidosis treatment during the course of the study
• Pulmonary hypertension related to etiology other than sarcoidosis (i.e. HIV, scleroderma, chronic thromboemboli)
• Use within 1 month of an sildenafil or vardenafil
• WHO functional class IV status
• Patients with severe other organ disease felt by investigators to impact on survival during the course of the study
• Subjects with liver function abnormalities (ALT or AST > 3 times the upper limit of normal at screening or at baseline) or chronic liver disease
• Advanced kidney failure (GFR < 30 ml/min at screening or at baseline)
• History of hypersensitivity reaction or adverse effect related to tadalafil
• Pregnant or lactating women
• Concomitant use of nitrates (any form) either regularly or intermittently
• Concomitant use of potent CYP3A inhibitors (eg, ritonavir, ketoconazole, itraconazole)
• Any additional contraindications and precautions specified in the package inserts for Tadalafil (Adcirca) not listed above

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sarcoid Associated Pulm. Hypertension	Tadalafil	Single-arm open-label proof of concept study of tadalafil in patients with sarcoidosis associated pulmonary hypertension.

Primary Outcome Measures

Name	Time	Method
6 Minute Walk Distance	Baseline, Week 8, Week 16, Week 24

Secondary Outcome Measures

Name	Time	Method
Resting Oxygen Saturation	Baseline, Week 24	Percent oxygen saturation of hemoglobin as measured by pulse oximetry in the resting state.
Short Form-36 Global Score	Baseline, Week 8, Week 16, Week 24	SF- 36 investigates the standard of quality of life through a general health assessment and not specific to a particular disease, age or treatment group. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. The global score is determined by taking an average of the individual domain scores. The global score range is from 0 (worst) to 100 (best).
St. George's Respiratory Questionnaire (SGRQ) Score	Baseline, Week 8, Week 16, Week 24	The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life)
Number of Participants With Change in WHO Functional Class (WHO FC)	Baseline, Week 24	The WHO functional classification ranges from I (patient's disease does not affect daily activities) to IV (patient's disease causes severe impairment). Higher scores indicate more severe impairment.
Brain Natriuretic Peptide Level	Baseline, Week 8, Week 16, Week 24
Oxygen Desaturation During 6 Minute Walk Test	Baseline, Week 24	Change (decrease) in oxygen saturation from start of 6 minute walk to nadir during the 6 minute walk test
Maximum Borg Dyspnea Score During 6 Minute Walk Test	Baseline, Week 8, Week 16, Week 24	The modified Borg scale consists of a vertical scale labelled 0 to10 with corresponding verbal expressions of progressively increasing sensation (shortness of breath) intensity. 0 represents no dyspnea, and 10 is the highest level of perceived dyspnea.

Trial Locations

Locations (2)

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States