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

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 ( V · o 2 ) during exercise at 12 months. Changes in systemic blood pressure and/or oxyhemoglobin saturation (SaO 2 ) 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.