Tadalafil for Pulmonary Hypertension Due to Chronic Lung Disease
Condition: Pulmonary Hypertension; Chronic Obstructive Pulmonary Disease (COPD)
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Hypertension, Pulmonary; Hypertension
Intervention: Tadalafil; placebo
Intervention description: Daily use of study drug to treat pulmonary hypertension.; Daily use in double blind study.
Intervention MeSH terms: Tadalafil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 44.0
Sex: All
Minimum age: 40 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Randomized trial; COPD; tadalafil; Phosphodiesterase inhibitor; Pulmonary hypertension

Summary:

      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.
    

Eligibility 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; 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 >25 mm Hg

               -  PVR >2.5 Wood units

               -  pulmonary artery capillary wedge pressure 18 mm Hg or less 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.