A Randomized, Double-blind, Placebo-controlled, Multicentre Trial, Assessing the Impact of Ferric Carboxymaltose on Exercise Capacity and Functional Status in Pulmonary Hypertension
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 306
- 试验地点
- 7
- 主要终点
- Change in 6MWD
研究概览
简要总结
Pulmonary hypertension (PH) is a condition characterized by elevated blood pressure in the pulmonary arteries. This leads to symptoms such as shortness of breath and a significantly reduced exercise capacity, resulting in a very poor quality of life. Currently, treatment options for PH are limited.
More than 60% of patients with PH develop iron deficiency. Studies have shown that this deficiency is associated with more severe symptoms, reduced exercise capacity, and even lower quality of life. Oral iron supplements are often ineffective in these patients due to impaired absorption in the intestines, caused by chronic low-grade inflammation-a common feature in PH.
Intravenous iron administration can rapidly correct the deficiency, but it remains unclear whether this also leads to clinical improvements such as enhanced exercise capacity, reduced shortness of breath, and improved quality of life. Moreover, the cost-effectiveness of this treatment is still unknown. The IRON-PH study aims to answer these questions.
As part of the IRON-PH study, 306 patients with pulmonary hypertension will be enrolled. Each patient will be randomized to receive either intravenous iron (ferric carboxymaltose) or intravenous placebo (NaCl 0.9%).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years of age
- •WHO functional class II - IV
- •Iron deficiency defined as TSAT <21% (no more than ≥3 months old at randomization)
- •PH defined by echocardiography and/or right heart catheterization (RHC) according to the following WHO groups:
- •Group 1 PH:
- •Patients with a diagnosis of idiopathic PAH, hereditary PAH, drug induced PAH or PAH and associated with CTD or CHD (historical RHC available) on stable and optimized doses of PAH targeted therapies for at least 4 weeks before randomization.
- •Echocardiographic evidence of a high or intermediate probability for PH as per 2022 ESC PH guidelines.
- •Group 2 PH and baseline LVEF > 50% on imaging modality within last 6 months before randomization and on stable doses of loop diuretics and HFpEF therapies for 4 weeks. Group 2 PH can be included based on echocardiography or RHC.:
- •Echocardiography (<6mo before randomization):
- •Presence of LVH or LA-enlargement
- •E/e' >15 (at rest or exercise)
- •TRVmax >2.8 m/s (at rest) or mPAP/CO>3 mHg/L/min (exercise) or echocardiographic evidence of high or intermediate probability for PH as per 2022 ESC PH guidelines.
- •RHC (<6mo before randomization)
- •mPAP > 20 mmHg
- •PCWP > 15 mmHg at rest or PCWP/CO-slope > 2mmHg/L/min or exercise PCWP>25mmHg, or PCWP 13-15 mmHg with elevation ≥18mmHg after 500 cc Fluid Challenge
- •Group 4 PH:
- •Inoperable CTEPH
- •Persistent/recurrent CTEPH (> 1 year after endarterectomy or > 6 months after balloon pulmonary angioplasty) ineligible for balloon pulmonary angioplasty.
- •Echocardiographic evidence of a high or intermediate probability for PH as per 2022 ESC PH guidelines.
排除标准
- •Screening haemoglobin < 8 g/dl or >15 g/dl
- •Ferritin > 700 ng/mL
- •Known hypersensitivity reaction to any component of FCM
- •Group 1 PH associated with veno-occlusive diseases.
- •Primary diagnosis of group 3 PH
- •Primary diagnosis of group 5 PH
- •Treatment with oral or other IV iron therapies at screening.
- •Current or planned mechanical circulatory support or lung/heart transplantation.
- •Any planned surgery or procedure leading to expected significant blood loss (defined as more than 250 ml = equal to 125mg of iron).
- •Haemodialysis or peritoneal dialysis (current or planned within the next 24 weeks).
- •Inability to return for follow up visits within the necessary windows
- •Concurrently in a study with another investigational product.
- •Uncorrected moderate to severe aortic stenosis (AVA <1.5cm² and mean gradient >20 mmHg) or severe valvular regurgitation (except tricuspid regurgitation)
- •Impression by investigator that patient cannot perform a 6MWT
- •Active infection as judged by the investigator.
- •Pregnancy or desire to become pregnant during the study duration.
研究组 & 干预措施
Ferric carboxymaltose
干预措施: Ferric Carboxymaltose (FCM) (Drug)
Placebo
干预措施: Sodium Chloride (NaCl) 0.9 % (Drug)
结局指标
主要结局
Change in 6MWD
时间窗: From baseline to 24 week follow-up
Change in 6-minute walking distance (6MWD) from baseline to 24 week follow-up
次要结局
- Change in MLHFQ(Baseline to 24 week follow-up)
- Change in EQ5D5L(Baseline to 24 week follow-up)
- Change in FSS(Baseline to 24 week follow-up)
- Developing composite clinical worsening event(From first patient Day 1 (Baseline) to study completion, an average of 2 years)