Acute hemodynamic effects of TPN171H in pulmonary arterial hypertension: a randomized, controlled, phase 2a trial

Clinical Snapshot

Key Findings

• P Value: TPN171H 5mg: p = 0.008

• Effect Size: TPN171H 5mg: -16.8% reduction vs placebo; TPN171H 10mg: non-significant; Tadalafil 20mg: -15.4%; Tadalafil 40mg: -13.3%

• Primary Outcome: Maximum change in pulmonary vascular resistance from baseline over 24 hours

• Nnt Or Sensitivity: Not calculable from hemodynamic data; would require clinical endpoint definition

• Confidence Interval: TPN171H 5mg: 95% CI -29.1 to -4.5%

Clinical Application

Limited by need for invasive hemodynamic monitoring; requires specialized PAH centers Would require TGA approval for clinical use; PAH management typically follows international guidelines through specialized centers; PBS listing would depend on long-term efficacy and safety data Adults with confirmed pulmonary arterial hypertension suitable for right heart catheterization

Abstract

Pulmonary arterial hypertension (PAH) has a poor prognosis despite available treatments. TPN171H, structurally modified from traditional Chinese medicine (Epimedium), was reported to have a high affinity for phosphodiesterase type 5 and exhibited anti-inflammatory and vasodilatory effects in preclinical studies. This phase 2a randomized trial (NCT04483115) evaluated the hemodynamic effects and safety of TPN171H in PAH. Sixty patients with PAH were randomly assigned to receive placebo, TPN171H (2.5, 5, or 10 mg) or tadalafil (20 or 40 mg) and evaluated for hemodynamic changes for 24 h. The primary endpoint was the maximum change (%) in pulmonary vascular resistance (PVR) from baseline. The key secondary endpoint was the change (%) in PVR to systemic vascular resistance (SVR) ratio at each observation point from baseline. Compared to the placebo group, the least square mean differences in the maximum change in PVR were -16.8% (95% CI, -29.1 to -4.5, p = 0.008) in TPN171H 5 mg, -15.4% (95% CI, -28.2 to -2.7, p = 0.019) in tadalafil 20 mg, and -13.3% (95% CI, -25.6 to -0.9, p = 0.036) in the tadalafil 40 mg group. Moreover, TPN171H 5 mg, but none of the tadalafil doses, showed a significant reduction in PVR/SVR ratio at 2 h (p = 0.026), 3 h (p = 0.030), and 5 h (p = 0.046) compared to the placebo group. No serious adverse events occurred. TPN171H 5 mg demonstrated favorable acute hemodynamic effects and an acceptable short-term safety profile in this exploratory trial, supporting further evaluation in adequately powered trials.

References

1. 1.Zhou, Y. P., Qiu, L. H., Ma, W., Cao, Y. S., Li, J., Huang, W., Wang, L., Wang, D. W., Duan, H. Q., Wang, Z., Jiang, X., Xu, X. Q., Ma, W. G., Huo, Y., & Jing, Z. C. (2026). Acute hemodynamic effects of TPN171H in pulmonary arterial hypertension: a randomized, controlled, phase 2a trial. Signal Transduction and Targeted Therapy. https://doi.org/10.1007/s11030-024-11016-2