title: Study design and rationale for investigating phosphodiesterase type 5 inhibition for the treatment of pulmonary hypertension due to chronic obstructive lung disease: the TADA-PHiLD (TADAlafil for Pulmonary Hypertension associated with chronic obstructive Lung Disease) trial.
abstract: In patients with chronic obstructive pulmonary disease (COPD), moderate or severe pulmonary hypertension (COPD-PH) is associated with increased rates of morbidity and mortality. Despite this, approaches to treatment and the efficacy of phosphodiesterase type 5 inhibition (PDE-5i) in COPD-PH are unresolved. We present the clinical rationale and study design to assess the effect of oral tadalafil on exercise capacity, cardiopulmonary hemodynamics, and clinical outcome measures in COPD-PH patients. Male and female patients 40-85 years old with GOLD stage 2 COPD or higher and pulmonary hypertension diagnosed on the basis of invasive cardiac hemodynamic assessment (mean pulmonary artery pressure [mPAP] >30 mmHg, pulmonary vascular resistance [PVR] >2.5 Wood units, and pulmonary capillary wedge pressure ≤18 mmHg at rest) will be randomized at a 1∶1 ratio to receive placebo or oral PDE-5i with tadalafil (40 mg daily for 12 months). The primary end point is change from baseline in 6-minute walk distance at 12 months. The secondary end points are change from baseline in PVR and mPAP at 6 months and change from baseline in peak volume of oxygen consumption ([Formula: see text]) during exercise at 12 months. Changes in systemic blood pressure and/or oxyhemoglobin saturation (Sao2) at rest and during exercise will function as safety outcome measures. TADA-PHiLD (TADAlafil for Pulmonary Hypertension assocIated with chronic obstructive Lung Disease) is the first sufficiently powered randomized clinical trial testing the effect of PDE-5i on key clinical and drug safety outcome measures in patients with at least moderate PH due to COPD.
authors.affiliation: Department of Cardiology, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA ; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Maron
authors.affiliation: Department of Medicine, Pulmonary and Critical Care Medicine Section, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA.
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Goldstein
authors.affiliation: Providence Veterans Affairs Medical Center, Providence, Rhode Island, USA; and Department of Medicine, Alpert Medical School of Brown University, Providence, Rhode Island, USA.
authors.forename: Sharon I
authors.initials: SI
authors.lastname: Rounds
authors.affiliation: Department of Cardiology, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA.
authors.forename: Shelley
authors.initials: S
authors.lastname: Shapiro
authors.affiliation: Providence Veterans Affairs Medical Center, Providence, Rhode Island, USA; and Department of Medicine, Alpert Medical School of Brown University, Providence, Rhode Island, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Jankowich
authors.affiliation: Department of Medicine, Pulmonary and Critical Care Medicine Section, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA ; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Garshick
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA ; Department of Medicine, Pulmonary and Critical Care Medicine Section, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA.
authors.forename: Marilyn L
authors.initials: ML
authors.lastname: Moy
authors.affiliation: Boston University School of Public Health, Boston, Massachusetts, USA; and Veterans Affairs Cooperative Studies Program, Boston, Massachusetts, USA.
authors.forename: David
authors.initials: D
authors.lastname: Gagnon
authors.affiliation: Providence Veterans Affairs Medical Center, Providence, Rhode Island, USA; and Department of Medicine, Alpert Medical School of Brown University, Providence, Rhode Island, USA.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Choudhary
keywords: clinical trial; phosphodiesterase inhibitor; pulmonary hypertension; tadalafil