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Tadalafil for Sarcoidosis Associated Pulmonary Hypertension (SAPH)

Primary Purpose

Pulmonary Hypertension

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tadalafil
Sponsored by
University of North Carolina, Chapel Hill
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Hypertension focused on measuring Sarcoidosis Associated Pulmonary Hypertension

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of North Carolina at Chapel Hill
  • University of Cincinnati

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sarcoid Associated Pulm. Hypertension

Arm Description

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

Outcomes

Primary Outcome Measures

6 Minute Walk Distance

Secondary Outcome Measures

Resting Oxygen Saturation
Percent oxygen saturation of hemoglobin as measured by pulse oximetry in the resting state.
Oxygen Desaturation During 6 Minute Walk Test
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
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.
Brain Natriuretic Peptide Level
Short Form-36 Global Score
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
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)
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.

Full Information

First Posted
March 24, 2011
Last Updated
June 25, 2017
Sponsor
University of North Carolina, Chapel Hill
Collaborators
Eli Lilly and Company, United Therapeutics, University of Cincinnati
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1. Study Identification

Unique Protocol Identification Number
NCT01324999
Brief Title
Tadalafil for Sarcoidosis Associated Pulmonary Hypertension
Acronym
SAPH
Official Title
Tadalafil for Sarcoidosis Associated Pulmonary Hypertension
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
October 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
Eli Lilly and Company, United Therapeutics, University of Cincinnati

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Hypertension
Keywords
Sarcoidosis Associated Pulmonary Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sarcoid Associated Pulm. Hypertension
Arm Type
Experimental
Arm Description
Single-arm open-label proof of concept study of tadalafil in patients with sarcoidosis associated pulmonary hypertension.
Intervention Type
Drug
Intervention Name(s)
Tadalafil
Intervention Description
20mg/day for one month then 40mg/day for additional 4 months
Primary Outcome Measure Information:
Title
6 Minute Walk Distance
Time Frame
Baseline, Week 8, Week 16, Week 24
Secondary Outcome Measure Information:
Title
Resting Oxygen Saturation
Description
Percent oxygen saturation of hemoglobin as measured by pulse oximetry in the resting state.
Time Frame
Baseline, Week 24
Title
Oxygen Desaturation During 6 Minute Walk Test
Description
Change (decrease) in oxygen saturation from start of 6 minute walk to nadir during the 6 minute walk test
Time Frame
Baseline, Week 24
Title
Maximum Borg Dyspnea Score During 6 Minute Walk Test
Description
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.
Time Frame
Baseline, Week 8, Week 16, Week 24
Title
Brain Natriuretic Peptide Level
Time Frame
Baseline, Week 8, Week 16, Week 24
Title
Short Form-36 Global Score
Description
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).
Time Frame
Baseline, Week 8, Week 16, Week 24
Title
St. George's Respiratory Questionnaire (SGRQ) Score
Description
The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life)
Time Frame
Baseline, Week 8, Week 16, Week 24
Title
Number of Participants With Change in WHO Functional Class (WHO FC)
Description
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.
Time Frame
Baseline, Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hubert J Ford, M.D.
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
28090299
Citation
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.
Results Reference
derived

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Tadalafil for Sarcoidosis Associated Pulmonary Hypertension

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