Results of the MACiTEPH study of macitentan for the treatment of inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension.

BACKGROUND

In a phase 2 study of inoperable chronic thromboembolic pulmonary hypertension (CTEPH), macitentan 10 mg improved hemodynamics and exercise capacity.

METHODS

MACiTEPH (NCT04271475) was a prospective, double-blind, placebo-controlled, phase 3 study. Adult patients with inoperable CTEPH (with/without balloon pulmonary angioplasty [BPA]) or persistent/recurrent CTEPH after pulmonary endarterectomy (PEA) (with/without BPA) were randomized 1:1 to macitentan 75 mg or placebo once daily. Primary endpoint was change from baseline to Week 28 in 6-minute walk distance (6MWD).

RESULTS

Following a pre-planned interim analysis, the study was stopped for futility. 127 patients were randomized, predominantly with inoperable CTEPH with BPA (36.2%) or persistent/recurrent CTEPH after PEA without BPA (30.7%). The majority (81.9%) were receiving pulmonary hypertension (PH)-specific therapy at baseline. 47 patients in the macitentan 75 mg and 48 in the placebo group had Week 28 assessments. Primary endpoint was not met; mean change in 6MWD from baseline to Week 28 versus placebo was -16.1 m (95% confidence limit: -32.3, 0.16). Clinical worsening events occurred in 6.3% and 14.3% of patients in the macitentan 75 mg and placebo groups, respectively. A slightly higher proportion of the macitentan 75 mg group had ≥1 adverse event (AE) or serious AE versus placebo; no pattern was identified. More patients in macitentan 75 mg versus placebo group discontinued treatment due to an AE (21.9% versus 7.9%, respectively).

CONCLUSIONS

MACiTEPH was discontinued for futility, as no treatment effect on 6MWD (primary endpoint) was observed. Despite the higher discontinuation rate in the macitentan 75 mg group, no unexpected safety signals were observed in CTEPH patients.