Trial record 2 of 75 for:    Pulmonary Hypertension | Open Studies | NIH, U.S. Fed

Tadalafil for Pulmonary Hypertension Due to Chronic Lung Disease (TADA-PHILD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Department of Veterans Affairs
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT01862536
First received: May 15, 2013
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

The functional, social, and economic burden of chronic obstructive lung disease (COPD) on the healthcare system is extraordinary. COPD is the fourth leading cause of death in the United States, and some estimates attribute up to $33.2 billion in health care costs to COPD-associated morbidity and mortality annually. The burden of COPD to the VA Healthcare system parallels these findings. According to the VA HSR&D Health Economics Resource Center, COPD ranks 5th among the 40 most common chronic clinical conditions in the U.S. Veteran patient population, is responsible for >14,000 VA hospital admission annually, and increases by $1,051/patient the total annual health care cost burden on the VA Healthcare system. Importantly, COPD is associated with frequent emergency room visitation and/or hospitalization patients. Pulmonary hypertension is a common co-morbid condition that worsen morbidity and mortality in patients with COPD. This study will examine the potential for tadalafil, a phosphodiesterase type-5 (PDE-5) inhibitor to improve functional status by decreasing pulmonary hypertension. Results from this study are expected to define the potential use of PDE-5 inhibitors in COPD-induced pulmonary hypertension. If successful, this treatment option may improve quality of life and outcomes for the large number of veterans afflicted with PH due to COPD.


Condition Intervention
Pulmonary Hypertension
Chronic Obstructive Pulmonary Disease (COPD)
Drug: Tadalafil
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Tadalafil for Pulmonary Hypertension Associated With Chronic Lung Disease

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Change in 6 minute walk test [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Change from baseline in distance walked in 6 minutes.


Secondary Outcome Measures:
  • Maximum volume of oxygen extraction on exercise testing [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Measure of aerobic fitness on exercise

  • Pulmonary vascular resistance [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Pulmonary vascular resistance assessed on right heart catheterization is a hemodynamic measurement of pulmonary vascular remodeling.

  • Mean pulmonary artery pressure [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Mean pulmonary artery pressure assessed by right heart catheterization is a hemodynamic measurement of pulmonary hypertension severity.

  • Tricuspid annular plane excursion (TAPSE) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The tricuspid annular plane excursion is an echocardiographic measurement of right ventricular systolic dysfunction.

  • Dyspnea and health related quality of life (HRQL) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Survey-based assessment of patient-reported changes to symptoms and quality of life following study drug treatment.

  • N-type brain natriuretic peptide (BNP) concentration [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Plasma BNP concentration is a biochemical marker that correlates positively with pulmonary hypertension severity.

  • Resting Hypoxemia [ Time Frame: Early (4 hours and 3 days following treatment) and late (1, 3, 6, 9, 12 months following treatment) ] [ Designated as safety issue: Yes ]
    Changes to resting peripheral oxyhemoglobin saturation levels will be used to assess the safety of the study drug in patients with chronic lung diseases.

  • Exercise-induced hypoxemia [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Changes to peripheral oxyhemoglobin saturation levels on exercise will be used to assess the safety of the study drug in patients with chronic lung diseases.


Estimated Enrollment: 150
Study Start Date: October 2013
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo tablet
Drug: placebo
Daily use in double blind study.
Experimental: Tadalafil
Daily use of tadalafil (study drug) at 40 mg orally.
Drug: Tadalafil
Daily use of study drug to treat pulmonary hypertension.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   40 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female U.S. Veteran patients 40-85 years old, with Gold Stage II COPD by pulmonary function testing (FEV1/FVC <0.70; FEV1 <79%) performed within 6 months of recruitment.
  • Eligible subjects must have PH documented on transthoracic echocardiogram within 6 months of baseline visit demonstrating an RV systolic pressure >40mmHg. To confirm the presence of PH, a right-heart catheterization will be performed, with subjects randomized to treatment only if catheterization shows a:

    • mPAP >30 mm Hg
    • PVR >2.5 Wood units
    • pulmonary artery capillary wedge pressure 18 mm Hg at rest
  • PH belonging to the following subgroup of the updated Dana Point Clinical Classification:

    • Group 3 (PH associated with lung disease and/or hypoxemia) specifically, Group 3.1 (chronic obstructive pulmonary disease [COPD]) as the major criteria. Patients may also have minor clinical features associated with 3.2 (Interstitial disease) (such as mild fibrosis on high resolution chest CT, but total lung capacity>80% predicted) and 3.3 (sleep disordered breathing) (AHI <15 or 20/hour).
  • 6-minute walk distance between 50-450 meters at screening visit.

Exclusion Criteria:

  • PH belonging to the following subgroups of the updated Dana Point Clinical Classification:

Group 1

  • Idiopathic
  • heritable
  • drug or toxin-induced
  • Associated Pulmonary Arterial Hypertension (APAH) with:

    • connective tissue disease
    • congenital heart disease
    • or HIV

Group 2

  • left atrial hypertension

Group 4

  • chronic thromboembolic PH
  • or other forms of PH not associated with primary lung disease

Also

  • Patients with a history of systemic hypotension in the ambulatory setting (reproducible measurements of systolic blood pressure <89 mmHg) on chart review.
  • Patients with moderate or severe hepatic impairment (Child-Pugh B and C)
  • Patients with severe renal insufficiency (GFR <30 ml/min/1.73 m2)
  • Severe aortic stenosis (aortic valve area <1.0 cm2)
  • Patients with any acute or chronic impairment:

    • (other than dyspnea), limiting the ability to comply with the study requirements, including the 6-minute walk test and right heart catheterization.
  • Patients with a recent stroke
  • Patients with untreated hypoxemia (SaO2 <92%) at rest
  • Patients with untreated moderate or severe obstructive sleep apnea (AHI>15)
  • Patients with any coagulopathy
  • Patients requiring nitrate therapy for any clinical indication
  • Patients with an active prescription for pulmonary vasodilator medication other than oxygen
  • Patients with a history of nonarteritic anterior ischemic optic neuropathy
  • Contraindication to tadalafil use including allergy to:

    • any PDE-5 inhibitor
    • anatomical deformations of the penis
    • sickle cell anemia
    • multiple myeloma
    • leukemia
    • bleeding disorders
    • active peptic ulcer disease
    • retinitis pigmentosa or other retinal disorders.
  • DlCO less than 30% of predicted
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01862536

Contacts
Contact: Ronald H Goldstein, MD (857) 203-6578 Ronald.Goldstein@va.gov
Contact: Bradley A Maron, MD (617) 525-4857 bmaron@partners.org

Locations
United States, California
VA Greater Los Angeles Healthcare System, West Los Angeles, CA Recruiting
West Los Angeles, California, United States, 90073
Contact: Shelley Shapiro    310-268-4314    shelley.shapiro@va.gov   
United States, Massachusetts
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA Recruiting
Boston, Massachusetts, United States, 02130
Contact: Paul R Conlin, MD    (857) 203-5111    Paul.Conlin@va.gov   
Contact: Terence M Keane, PhD    (857) 364-4551    terry.keane@va.gov   
Principal Investigator: Ronald Howard Goldstein, MD         
United States, Rhode Island
Providence VA Medical Center, Providence, RI Recruiting
Providence, Rhode Island, United States, 02908
Contact: Sharon I Rounds    401-457-3020    sharon.rounds@va.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Ronald Howard Goldstein, MD VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT01862536     History of Changes
Other Study ID Numbers: CLIN-008-12F
Study First Received: May 15, 2013
Last Updated: May 15, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
Randomized trial
COPD
tadalafil
Phosphodiesterase inhibitor
Pulmonary hypertension

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Vascular Diseases
Cardiovascular Diseases
Respiratory Tract Diseases
Phosphodiesterase Inhibitors
Tadalafil
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Phosphodiesterase 5 Inhibitors
Urological Agents

ClinicalTrials.gov processed this record on August 25, 2014