Tadalafil for Sarcoidosis Associated Pulmonary Hypertension

NCT01324999 | Completed Phase 2 Results DMC

• 1 other identifier: 09-2326
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

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

Conditions

Pulmonary Hypertension

Keywords

Sarcoidosis Associated Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• 6 Minute Walk Distance

  Baseline, Week 8, Week 16, Week 24

Secondary Outcomes (7)

• Resting Oxygen Saturation

  Baseline, Week 24

• Oxygen Desaturation During 6 Minute Walk Test

  Baseline, Week 24

• Maximum Borg Dyspnea Score During 6 Minute Walk Test

  Baseline, Week 8, Week 16, Week 24

• Brain Natriuretic Peptide Level

  Baseline, Week 8, Week 16, Week 24

• Short Form-36 Global Score

  Baseline, Week 8, Week 16, Week 24

Study Arms (1)

Sarcoid Associated Pulm. Hypertension

EXPERIMENTAL

Single-arm open-label proof of concept study of tadalafil in patients with sarcoidosis associated pulmonary hypertension.

Drug: Tadalafil

Interventions

Tadalafil DRUG

20mg/day for one month then 40mg/day for additional 4 months

Sarcoid Associated Pulm. Hypertension

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Eli Lilly and Company: collaborator
• United Therapeutics: collaborator
• University of Cincinnati: collaborator

Study Sites (2)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Related Publications (1)

• Ford HJ, Baughman RP, Aris R, Engel P, Donohue JF. Tadalafil therapy for sarcoidosis-associated pulmonary hypertension. Pulm Circ. 2016 Dec;6(4):557-562. doi: 10.1086/688775.

  PMID: 28090299 DERIVED

MeSH Terms

Conditions

Hypertension, Pulmonary

Interventions

Tadalafil

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Limitations and Caveats

Since this was a proof of concept study evaluating safety and tolerability of the intervention in this population, it was not powered to achieve statistical significance in changes observed from baseline to week 24 in any of the endpoints.

Results Point of Contact

• Title: H. James Ford, MD
• Organization: University of North Carolina at Chapel Hill

hjford@med.unc.edu

(919) 966-2531

Study Officials

• Hubert J Ford, M.D.

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: March 24, 2011
• First Posted: March 29, 2011
• Study Start: March 1, 2011
• Primary Completion: July 1, 2013
• Study Completion: October 1, 2013
• Last Updated: July 24, 2017
• Results First Posted: July 24, 2017

Record last verified: 2017-06

Locations

US (2)