Phase 2 Study to Evaluate the Efficacy and Safety of Inhaled Nitric Oxide Therapy in Patients With Severe Right Heart Failure Associated With Pulmonary Hypertension　― Protocol for the PHiNO Study ―

Abstract

Background: Acute right heart failure (RHF) is a syndrome characterized by sudden right ventricular dysfunction leading to systemic hypoperfusion, which carries a poor prognosis, particularly in patients with pulmonary hypertension (PH). Early reduction of pulmonary vascular resistance (PVR) is crucial for improving RHF and reducing acute mortality. Compared with pulmonary vasodilators approved for pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH), inhaled nitric oxide (iNO) therapy has the advantages of being fast acting, an excellent selective pulmonary vasodilation, and has less effect on systemic blood pressure.

Methods and Results: We describe a phase II, investigator-initiated, randomized, open-label trial (Japan Registry of Clinical Trials jRCT2051220042) to evaluate the efficacy and safety of iNO therapy (INOflo® for inhalation 800 ppm), as an acute-phase treatment for severe RHF associated with PAH or CTEPH over a 1-week course. Thirty patients will be enrolled and randomized to receive the study drug, or not, in addition to conventional therapy. The primary endpoint is the change in PVR from baseline to 30 min after the start of inhalation, measured using right heart catheterization. Secondary endpoints include changes in hemodynamic parameters, arterial blood tests, and echocardiography findings, and the safety of iNO therapy, assessed through blood methemoglobin concentration, blood pressure, and adverse events.

Conclusions: iNO therapy is expected to play a significant role in rapidly improving acute severe RHF associated with PH.