Supplementation of iron in pulmonary hypertension: Rationale and design of a phase II clinical trial in idiopathic pulmonary arterial hypertension.
Supplementation of iron in pulmonary hypertension: Rationale and design of a phase II clinical trial in idiopathic pulmonary arterial hypertension.
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DOI：
10.4103/2045-8932.109923
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发表时间：
2013-01
影响因子：
2.6
通讯作者：
Wilkins MR
中科院分区：
文献类型：
--
作者：
Howard LS;Watson GM;Wharton J;Rhodes CJ;Chan K;Khengar R;Robbins PA;Kiely DG;Condliffe R;Elliott CA;Pepke-Zaba J;Sheares K;Morrell NW;Davies R;Ashby D;Gibbs JS;Wilkins MR
我们的目的是评估静脉铁剂（Ferinject）输注在铁缺乏伴特发性肺动脉高压（IPAH）患者中的安全性和潜在临床获益。在没有贫血的情况下，缺铁（1）在IPAH患者中很常见;（2）与铁调素（铁稳态的关键调节剂）水平不适当升高有关;（3）与疾病严重程度和更差的临床结局相关。铁调素水平升高导致的吸收减少可能会阻碍口服铁吸收。肠外补铁治疗IPAH的安全性和获益尚不清楚。补充铁治疗肺动脉高压（SIPHON）是一项II期、多中心、双盲、随机、安慰剂对照、交叉临床试验，研究铁在IPAH中的作用。治疗12周后，至少60名患者将随机接受静脉内羧基麦芽糖铁（Ferinject）或生理盐水安慰剂，交叉点。主要结局将是通过心导管插入术测量的12周时静息肺血管阻力相对于基线的变化。次要措施包括休息和运动血流动力学和运动性能从系列自行车递增和耐力心肺运动试验。其他次要测量包括血清铁指数、6分钟步行距离、WHO功能分级、生活质量评分、N末端脑钠肽前体（NT-proBNP）以及心脏磁共振的心脏解剖和功能。我们认为静脉补铁可改善IPAH患者的血流动力学和临床结局。如果数据支持潜在有用的治疗效果并表明该药物是安全的，则该研究将用于III期研究以解决疗效。
Our aim is to assess the safety and potential clinical benefit of intravenous iron (Ferinject) infusion in iron deficient patients with idiopathic pulmonary arterial hypertension (IPAH). Iron deficiency in the absence of anemia (1) is common in patients with IPAH; (2) is associated with inappropriately raised levels of hepcidin, the key regulator of iron homeostasis; and (3) correlates with disease severity and worse clinical outcomes. Oral iron absorption may be impeded by reduced absorption due to elevated hepcidin levels. The safety and benefits of parenteral iron replacement in IPAH are unknown. Supplementation of Iron in Pulmonary Hypertension (SIPHON) is a Phase II, multicenter, double-blind, randomized, placebo-controlled, crossover clinical trial of iron in IPAH. At least 60 patients will be randomized to intravenous ferric carboxymaltose (Ferinject) or saline placebo with a crossover point after 12 weeks of treatment. The primary outcome will be the change in resting pulmonary vascular resistance from baseline at 12 weeks, measured by cardiac catheterization. Secondary measures include resting and exercise hemodynamics and exercise performance from serial bicycle incremental and endurance cardiopulmonary exercise tests. Other secondary measurements include serum iron indices, 6-Minute Walk Distance, WHO functional class, quality of life score, N-terminal pro-brain natriuretic peptide (NT-proBNP), and cardiac anatomy and function from cardiac magnetic resonance. We propose that intravenous iron replacement will improve hemodynamics and clinical outcomes in IPAH. If the data supports a potentially useful therapeutic effect and suggest this drug is safe, the study will be used to power a Phase III study to address efficacy.
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DOI：
10.1161/hypertensionaha.110.160515
发表时间：
2010-12
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Park AM;Wong CM;Jelinkova L;Liu L;Nagase H;Suzuki YJ
通讯作者：
Suzuki YJ
影响因子：
158.5
作者：
Galiè, N;Ghofrani, HA;Simonneau, G
通讯作者：
Simonneau, G
影响因子：
158.5
作者：
Olschewski, H;Simonneau, G;Seeger, W
通讯作者：
Seeger, W
影响因子：
24
作者：
Okonko, Darlington O.;Grzeslo, Agnieszka;Ponikowski, Piotr
通讯作者：
Ponikowski, Piotr
影响因子：
3.5
作者：
Tay, Edgar L. W.;Peset, Ana;Gatzoulis, Michael A.
通讯作者：
Gatzoulis, Michael A.