Abstract：
Endothelin receptor antagonist (ERA) and phosphodiesterase 5 inhibitor (PDE5i) combination therapy is recommended for low-/intermediate-risk pulmonary arterial hypertension (PAH) patients. A fixed-dose combination of the ERA macitentan and PDE5i tadalafil (M/T FDC) in a once-daily, single tablet would simplify treatment.
The multicenter, double-blind, adaptive phase 3 A DUE study investigated the efficacy and safety of M/T FDC vs macitentan 10 mg and vs tadalafil 40 mg monotherapies in PAH patients, including treatment-naïve and prior ERA or PDE5i monotherapy-treated patients.
World Health Organization functional class II-III patients were randomized to M/T FDC, macitentan, or tadalafil depending on their PAH treatment (treatment-naïve, ERA, or PDE5i monotherapy) at baseline. The primary endpoint was change in pulmonary vascular resistance (PVR) at week 16.
In total, 187 patients were randomized to single-tablet M/T FDC (n = 108), macitentan (n = 35), or tadalafil (n = 44). PVR reduction with M/T FDC was significantly greater vs macitentan (29%; geometric mean ratio 0.71; 95% CL: 0.61-0.82; P < 0.0001) and vs tadalafil (28%; geometric mean ratio 0.72; 95% CL: 0.64-0.80; P < 0.0001). Three patients died in the M/T FDC arm (judged unrelated to treatment). Adverse events (AEs) leading to discontinuation, serious AEs, and those of special interest (anemia, hypotension, and edema) were more frequent with M/T FDC.
Macitentan and tadalafil FDC significantly improved PVR vs monotherapies in PAH patients, with a safety and tolerability profile consistent with the individual components. The A DUE study supports M/T FDC as a once-daily, single-tablet combination for initial therapy and escalation to double combination therapy in patients with PAH. (Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension [PAH]) [A DUE]; NCT03904693).
The multicenter, double-blind, adaptive phase 3 A DUE study investigated the efficacy and safety of M/T FDC vs macitentan 10 mg and vs tadalafil 40 mg monotherapies in PAH patients, including treatment-naïve and prior ERA or PDE5i monotherapy-treated patients.
World Health Organization functional class II-III patients were randomized to M/T FDC, macitentan, or tadalafil depending on their PAH treatment (treatment-naïve, ERA, or PDE5i monotherapy) at baseline. The primary endpoint was change in pulmonary vascular resistance (PVR) at week 16.
In total, 187 patients were randomized to single-tablet M/T FDC (n = 108), macitentan (n = 35), or tadalafil (n = 44). PVR reduction with M/T FDC was significantly greater vs macitentan (29%; geometric mean ratio 0.71; 95% CL: 0.61-0.82; P < 0.0001) and vs tadalafil (28%; geometric mean ratio 0.72; 95% CL: 0.64-0.80; P < 0.0001). Three patients died in the M/T FDC arm (judged unrelated to treatment). Adverse events (AEs) leading to discontinuation, serious AEs, and those of special interest (anemia, hypotension, and edema) were more frequent with M/T FDC.
Macitentan and tadalafil FDC significantly improved PVR vs monotherapies in PAH patients, with a safety and tolerability profile consistent with the individual components. The A DUE study supports M/T FDC as a once-daily, single-tablet combination for initial therapy and escalation to double combination therapy in patients with PAH. (Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension [PAH]) [A DUE]; NCT03904693).
摘要：
背景：内皮素受体拮抗剂（ERA）和磷酸二酯酶5抑制剂（PDE5i）联合治疗推荐用于低/中危肺动脉高压（PAH）患者。ERAMacitentan和PDE5i他达拉非（M/TFDC）的固定剂量组合，每天一次，单一片剂将简化治疗。
目标：多中心，双盲,适应性3期DUE研究调查了M/TFDC与10mg马西坦和40mg他达拉非单药治疗PAH患者的疗效和安全性，包括未治疗和既往ERA或PDE5i单一疗法治疗的患者。
方法：世界卫生组织功能II-III级患者被随机分配到M/TFDC，Macitentan,或他达拉非，取决于他们的PAH治疗(治疗-幼稚，ERA,或PDE5i单一疗法)在基线。主要终点是第16周时肺血管阻力（PVR）的变化。
结果：总计，187例患者被随机分配到单片M/TFDC（n=108），Macitentan(n=35),或他达拉非（n=44）。M/TFDC的PVR降低显著高于马西坦(29%;几何平均比0.71;95%CL:0.61-0.82;P<0.0001)和他达拉非(28%;几何平均比0.72;95%CL:0.64-0.80;P<0.0001)。三名患者在M/TFDC组中死亡（判断与治疗无关）。导致停药的不良事件(AE)，严重的AE，和那些特别感兴趣的(贫血，低血压,和水肿）在M/TFDC中更为常见。
结论：Macitentan和他达拉非FDC显著改善了PAH患者的PVR，具有与各个组件一致的安全性和耐受性。ADUE研究支持M/TFDC作为每日一次，PAH患者的初始治疗和双联合治疗的单片联合治疗。（比较Macitentan和他达拉非单药疗法与相应固定剂量联合疗法在肺动脉高压[PAH]受试者中的疗效和安全性的临床研究）[DUE]；NCT03904693）。
目标：多中心，双盲,适应性3期DUE研究调查了M/TFDC与10mg马西坦和40mg他达拉非单药治疗PAH患者的疗效和安全性，包括未治疗和既往ERA或PDE5i单一疗法治疗的患者。
方法：世界卫生组织功能II-III级患者被随机分配到M/TFDC，Macitentan,或他达拉非，取决于他们的PAH治疗(治疗-幼稚，ERA,或PDE5i单一疗法)在基线。主要终点是第16周时肺血管阻力（PVR）的变化。
结果：总计，187例患者被随机分配到单片M/TFDC（n=108），Macitentan(n=35),或他达拉非（n=44）。M/TFDC的PVR降低显著高于马西坦(29%;几何平均比0.71;95%CL:0.61-0.82;P<0.0001)和他达拉非(28%;几何平均比0.72;95%CL:0.64-0.80;P<0.0001)。三名患者在M/TFDC组中死亡（判断与治疗无关）。导致停药的不良事件(AE)，严重的AE，和那些特别感兴趣的(贫血，低血压,和水肿）在M/TFDC中更为常见。
结论：Macitentan和他达拉非FDC显著改善了PAH患者的PVR，具有与各个组件一致的安全性和耐受性。ADUE研究支持M/TFDC作为每日一次，PAH患者的初始治疗和双联合治疗的单片联合治疗。（比较Macitentan和他达拉非单药疗法与相应固定剂量联合疗法在肺动脉高压[PAH]受试者中的疗效和安全性的临床研究）[DUE]；NCT03904693）。
