Randomised, placebo-controlled trial of oral hymecromone in adults with pulmonary hypertension.

The extracellular matrix component hyaluronan (HA) is linked to vascular remodelling and interstitial fibrosis in PH.

细胞外基质成分透明质酸（HA）与PH中的血管重塑和间质纤维化有关。

We hypothesised that inhibition of HA synthesis with hymecromone could serve as a reverse-remodelling therapy in PH.

我们假设使用曲美克酮抑制透明质酸合成可以作为肺动脉高压（PH）的逆转重塑疗法。

Methods

We performed a proof-of-concept phase IIa randomised, double-blind, placebo-controlledstudy in adults with pulmonary arterial hypertension and PH associated with interstitial lung disease (PH-ILD).

我们在患有肺动脉高压和与间质性肺病相关的肺高压（PH-ILD）的成人中进行了一项概念验证的IIa期随机、双盲、安慰剂对照研究。

Patients were randomised to a 5:3 ratio and stratified by PH group to receive oral hymecromone or placebo two times per day over 24 weeks.

患者按照5:3的比例随机分配，并根据肺动脉高压（PH）组进行分层，每天两次口服黄嘌呤或安慰剂，持续24周。

The primary endpoint was change in pulmonary vascular resistance (PVR).

主要终点是肺血管阻力（PVR）的变化。

Results

We enrolled 16 patients with PH with a median age of 62.0 years.

我们招募了16名肺动脉高压（PH）患者，中位年龄为62.0岁。

There were no treatment-related adverse events leading to hymecromone discontinuation.

没有治疗相关的不良事件导致黄嘌呤醇停药。

No statistically significant difference in PVR was observed at 24 weeks for the experimental group compared with the placebo group (mean difference 0.61 Wood unit, 95% CI -1.5 to 2.7).

在24周时，实验组与安慰剂组在肺血管阻力（PVR）上未观察到统计学上的显著差异（平均差异0.61 Wood单位，95%置信区间-1.5至2.7）。

Five patients with PH-ILD treated with hymecromone demonstrated an unadjusted absolute mean increase in 6 min walk distance of 66 m (SD 69.6) from baseline to 24 weeks and improvements in quality-of-life measures.

五名接受曲美克隆治疗的肺动脉高压合并间质性肺病（PH-ILD）患者，在24周时与基线相比，未经调整的6分钟步行距离绝对平均增加66米（标准差69.6），生活质量指标有所改善。

Conclusions

Our exploratory analyses suggest that treatment with hymecromone could lead to improvements in clinically meaningful functional parameters in patients with PH-ILD.

我们的探索性分析表明，使用曲美克酮治疗可能在临床有意义的功能参数上对肺动脉高压合并间质性肺病（PH-ILD）患者产生改善。

Further investigations in larger patient cohorts are warranted.

有必要在更大的患者群体中进行进一步的研究。

trial_registration_number

ClinicalTrials.gov: NCT05128929.

ClinicalTrials.gov: NCT05128929。