Sotatercept for Combined Post- and Precapillary Pulmonary Hypertension Associated With Heart Failure: Results From the Phase 2, Randomized, Placebo-Controlled CADENCE Study.

Despite significant mortality, there are no proven therapies.

尽管死亡率显著，但没有经过证实的治疗方法。

Methods

In this multicenter, randomized, placebo-controlled, phase 2 trial, adults received sotatercept (0.3 or 0.7 mg/kg) or placebo every 3 weeks.

在这项多中心、随机、安慰剂对照的2期临床试验中，成年患者每3周接受一次sotatercept（0.3或0.7 mg/kg）或安慰剂治疗。

The primary end point was change in pulmonary vascular resistance at week 24.

主要终点是第24周时肺血管阻力的变化。

Hodges-Lehmann shift estimates described placebo-adjusted changes.

Hodges-Lehmann位移估计描述了安慰剂调整后的变化。

Results

A total of 164 patients were randomized 54:55:55 to sotatercept 0.3 mg/kg, 0.7 mg/kg, and placebo, and baseline median pulmonary vascular resistance was 5.2 (interquartile range, 4.0-6.9) Wood units.

共有164名患者按54:55:55的比例随机分配到sotatercept 0.3 mg/kg、0.7 mg/kg和安慰剂组，基线中位肺血管阻力为5.2（四分位数范围，4.0-6.9）Wood单位。

The median change from baseline in pulmonary vascular resistance at week 24 was -0.67 Wood units in the sotatercept 0.3 mg/kg group, -0.33 Wood units in the sotatercept 0.7 mg/kg group, and 0.26 Wood units in the placebo group.

在第24周时，0.3 mg/kg组的肺血管阻力基线中位数变化为-0.67 Wood单位，0.7 mg/kg组为-0.33 Wood单位，而安慰剂组为0.26 Wood单位。

The Hodges-Lehmann shift estimates in pulmonary vascular resistance were -1.02 Wood units (95% CI, -1.81 to -0.23; P=0.004) for 0.3 mg/kg and -0.75 Wood units (95% CI, -1.52 to 0.03; P=0.024) for 0.7 mg/kg sotatercept.

肺血管阻力的Hodges-Lehmann位移估计值在0.3 mg/kg组为-1.02 Wood单位（95%置信区间，-1.81至-0.23；P=0.004），而在0.7 mg/kg组为-0.75 Wood单位（95%置信区间，-1.52至0.03；P=0.024）。

Reductions were observed in mean pulmonary arterial pressure (0.3 and 0.7 mg/kg: -9.19 mm Hg [95% CI, -13.00 to -5.38] and -9.22 [95% CI, -12.97 to -5.46]) and pulmonary arterial wedge pressure (0.3 and 0.7 mg/kg: -3.04 mm Hg [95% CI, -5.77 to -0.32] and -2.53 [95% CI, -5.33 to 0.28]).

观察到平均肺动脉压的降低（0.3和0.7 mg/kg: -9.19 mm Hg [95% 置信区间, -13.00 到 -5.38] 和 -9.22 [95% 置信区间, -12.97 到 -5.46]）以及肺动脉楔压的降低（0.3和0.7 mg/kg: -3.04 mm Hg [95% 置信区间, -5.77 到 -0.32] 和 -2.53 [95% 置信区间, -5.33 到 0.28]）。

Changes in 6-minute walk distance were 20.3 m (95% CI, 1.5-39.1) for 0.3 mg/kg and 5.8 m (95% CI, -17.3 to 28.9) for 0.7 mg/kg sotatercept.

6分钟步行距离的变化为0.3 mg/kg时为20.3米（95% 置信区间, 1.5-39.1），而0.7 mg/kg sotatercept时为5.8米（95% 置信区间, -17.3 到 28.9）。

The most common adverse events with sotatercept (both groups) were increased hemoglobin and diarrhea.

sotatercept（两组）最常见的不良事件是血红蛋白增加和腹泻。

Conclusions

These findings provide proof of concept for improved pulmonary vascular and cardiac hemodynamics after activin signaling inhibition with sotatercept in patients with combined post- and precapillary pulmonary hypertension in heart failure with preserved ejection fraction.

这些发现为在心力衰竭并伴有射血分数保留的后前毛细血管性肺动脉高压患者中，使用sotatercept抑制激活素信号传导后改善肺血管和心脏血流动力学提供了概念验证。

registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT04945460.

网址: https://www.clinicaltrials.gov; 唯一标识符: NCT04945460.