A Phase 2, Randomized, Clinical Trial of Inhaled Nitric Oxide for Acute Severe Right Heart Failure With Pulmonary Hypertension (PHiNO Study)

Clinical Snapshot

Key Findings

• P Value: Not reported but CI excludes null

• Effect Size: Mean difference -3.21 Wood units favouring inhaled nitric oxide

• Primary Outcome: Change in pulmonary vascular resistance at 30 minutes

• Nnt Or Sensitivity: Not calculable from available data - surrogate endpoint study

• Confidence Interval: 95% CI: -4.633 to -1.785 Wood units

Clinical Application

Readily implementable in Australian tertiary hospitals with existing nitric oxide delivery systems Inhaled nitric oxide available through Special Access Scheme; aligns with intensive care guidelines for pulmonary hypertension management ICU patients with acute severe right heart failure secondary to pulmonary hypertension

Abstract

BACKGROUND: Acute right heart failure (RHF) is life threatening in patients with pulmonary hypertension (PH). This study investigated the efficacy and safety of inhaled nitric oxide (iNO; INOflo®for inhalation 800 ppm), a rapid pulmonary vasodilator, in patients with acute severe RHF due to PH. METHODS AND RESULTS: In this Phase 2 randomized controlled trial, 30 patients with acute severe RHF due to PH (pulmonary arterial hypertension or chronic thromboembolic PH) were randomized 1 : 1 to either an iNO or control group (which did not receive iNO). The primary endpoint was the change in pulmonary vascular resistance (PVR) from baseline to 30 min after either iNO initiation or patient registration and assignment (control group), which differed significantly between the iNO and control groups (mean [±SD] -2.41±2.47 vs. 0.8±1.03 Wood units, respectively; between group difference -3.21 [95% confidence interval -4.633, -1.785] Wood units). Serum B-type natriuretic peptide (BNP) levels and inferior vena cava diameter (secondary endpoints) decreased significantly in the iNO group over the 7-day study period. No serious adverse events, including methemoglobinemia, were observed. CONCLUSIONS: iNO significantly reduced PVR in patients with acute severe RHF due to PH, without serious adverse events. Serum BNP levels and inferior vena cava diameter improved in the iNO group. These findings suggest that iNO is a promising acute treatment option for RHF due to PH.

References

1. 1.Ogo, T., Ueda, J., Tsuji, A., Asano, R., Hayashi, H., Takano, R., Fujisaki, S., Asakura, K., & Yamamoto, H. (2026). A Phase 2, Randomized, Clinical Trial of Inhaled Nitric Oxide for Acute Severe Right Heart Failure With Pulmonary Hypertension (PHiNO Study). Circulation Journal. https://doi.org/10.1253/circj.CJ-26-0119