Tadalafil for Pulmonary Hypertension Due to Chronic Lung Disease

NCT01862536 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CLIN-008-12F
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Pulmonary Hypertension; Chronic Obstructive Pulmonary Disease (COPD)

Keywords

Randomized trial; COPD; tadalafil; Phosphodiesterase inhibitor; Pulmonary hypertension

Outcome Measures

Primary Outcomes (1)

• Change in 6 Minute Walk Test

  Change from baseline in distance walked in 6 minutes.

  The change in distance walked when assessed at 3 months following trial initiation as compared to baseline, similarly at 6 months compared to baseline, at 9 months compared to baseline and at 12 months compared to baseline.

Secondary Outcomes (8)

• Maximum VO2

  12 months

• Pulmonary Vascular Resistance

  6 months

• Mean Pulmonary Artery Pressure

  6 months

• Tricuspid Annular Plane Excursion (TAPSE)

  12 months

• St. George's Respiratory Questionnaire, Dyspnea and Health Related Quality of Life

  12 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo tablet

Drug: placebo

Tadalafil

EXPERIMENTAL

Daily use of tadalafil (study drug) at 40 mg orally.

Drug: Tadalafil

Interventions

Tadalafil DRUG

Daily use of study drug to treat pulmonary hypertension.

Also known as: Cialis

Tadalafil

placebo DRUG

Daily use in double blind study.

Placebo

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• minute walk distance between 50-450 meters at screening visit.

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (5)

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, 90073, United States

Location

VA Eastern Colorado Health Care System, Denver, CO

Denver, Colorado, 80220, United States

Location

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, 30033, United States

Location

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, 02130, United States

Location

Providence VA Medical Center, Providence, RI

Providence, Rhode Island, 02908, United States

Location

MeSH Terms

Conditions

Hypertension, Pulmonary; Pulmonary Disease, Chronic Obstructive

Interventions

Tadalafil

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Lung Diseases, Obstructive; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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

This trial did not reach its enrollment goals. Enrollment was limited because of the unexpected frailty of patients with advanced COPD and evidence of elevated pulmonary artery pressure as assessed by cardiac echo. In addition we found that many potential candidates were found to have features of both group II and group III PH.

Results Point of Contact

• Title: Dr. Ronald Goldstein
• Organization: VA Boston Healthcare System

Ronald.Goldstein@va.gov

857-203-6578

Study Officials

• Ronald H Goldstein, MD

  VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2013
• First Posted: May 24, 2013
• Study Start: October 1, 2013
• Primary Completion: August 31, 2019
• Study Completion: August 31, 2019
• Last Updated: March 9, 2021
• Results First Posted: March 9, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: \- Datasets meeting VA standards for disclosure to the public will be made available within 1 year of publication.
• Access Criteria: Investigators requesting a copy of a dataset will sign a Letter of Agreement or a Data Use Agreement. The recipient will not attempt to identify any individual whose data are in the dataset. A local privacy officer will certify that a dataset contains no PHI, PII, or VA Sensitive Information prior to release outside VA.

Locations

US (5)