What is the Effect of Intravenous Iron Supplementation on Cardiopulmonary Haemodynamics, Exercise Capacity and Quality of Life in Patients With IPAH and Iron Deficiency?
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 5
- 主要终点
- Change in Resting Pulmonary Vascular Resistance (PVR)
研究概览
简要总结
This study will establish whether intravenous iron replacement has clinical benefit in idiopathic pulmonary arterial hypertension.
A 24-week double-blind, randomised, placebo-controlled, crossover study will investigate whether a single dose of 1g of Ferinject® or CosmoFer improves cardiopulmonary haemodynamics, exercise capacity and quality of life and is well-tolerated.
IV iron formulation used in Europe - Ferinject IV iron formulation used in China - CosmoFer
详细描述
These results represent the outcome of two separate clinical trials which were conducted in collaboration, led by Imperial College and Fuwai, China respectively. The protocols were analogous, although in China Endurance Cardio-Pulmonary Exercise Testing (CPET) was not done and instead of Ferinject/Placebo being infused over 15 minutes, Cosmofer/Placebo was infused over 4-6 hours.
The study analyses were performed as Intention to Treat, except for patients 6009-6017 as described below. The study was a cross-over design and results are presented for 2 groups based on the participants' study timepoint, and presented separately for the two study datasets (Europe and Fuwai). A meta-analysis was conducted for the combined data where possible and the relevant p-values have been provided.
Iron results in the European dataset are taken from blood results which were collected centrally and analysed by one laboratory at Imperial College London. N-Terminal B-type natriuretic peptide (NT-PRO-BNP) and Soluble Transferrin Receptors (STFR) were not done at Fuwai.
The study was conducted according to Good Clinical Practice (GCP), but there were some missing data (imputed using multiple imputation techniques), and also some significant protocol deviations which are summarised below.
Six participants (2003, 3004, 4002-4005) had their endurance CPETs set at incorrect workloads which differed significantly from that achieved at the baseline incremental CPET. These data were therefore treated as missing, and relevant values imputed as per the statistical analysis plan.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Ferinject or CosmoFer followed by Placebo
IV iron formulation used in Europe - Ferinject - given over 15 minutes
IV iron formulation used in China - CosmoFer - over a period of 4 to 6 hours
IV Iron given at Week 0, Placebo (saline) given at Week 12.
干预措施: Saline (Drug)
Ferinject or CosmoFer followed by Placebo
IV iron formulation used in Europe - Ferinject - given over 15 minutes
IV iron formulation used in China - CosmoFer - over a period of 4 to 6 hours
IV Iron given at Week 0, Placebo (saline) given at Week 12.
干预措施: Ferinject or CosmoFer (Drug)
Placebo followed by Ferinject or CosmoFer
Placebo comparator
Placebo (saline) given at Week 0, IV Iron given at Week 12.
干预措施: Saline (Drug)
Placebo followed by Ferinject or CosmoFer
Placebo comparator
Placebo (saline) given at Week 0, IV Iron given at Week 12.
干预措施: Ferinject or CosmoFer (Drug)
结局指标
主要结局
Change in Resting Pulmonary Vascular Resistance (PVR)
时间窗: 12 weeks post study treatment
To be measured by cardiac catheterisation in wood units.
Change in Exercise Capacity - Endurance
时间窗: 12 Weeks post study treatment
Time measured in seconds from start to end of the endurance bicycle cardiopulmonary exercise testing at 80% of the peak work rate. Peak work rate is determined by that achieved at the baseline incremental cardiopulmonary exercise test (CPET). Note that this was the primary end-point of the European study. Endurance CPET was not done in China.
次要结局
- Oxygen Consumption (VO2) at 3 Minutes(12 weeks post study treatment)
- Iron Indices: Ferritin(12 weeks post study treatment)
- Oxygen Consumption (VO2) / Work Rate (WR) Slope(12 weeks post study treatment)
- Oxygen Consumption (VO2) at the End of Endurance Cardio-pulmonary Exercise Test (CPET)(12 weeks post study treatment)
- Oxygen Consumption (VO2) Level at Peak 12 Weeks After Study Treatment(12 weeks post study treatment)
- 6 Minute Walk Test: Borg Dyspnoea Score After Test(12 weeks post study treatment)
- Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR Questionnaire): Activity Score(12 weeks post study treatment)
- Mean Right Atrial Pressure (Cardiac Catheter)(12 weeks post study treatment)
- Ventilation / Volume of Exhaled Carbon Dioxide (VE/VCO2 Slope)(12 weeks post study treatment)
- Iron Indices: Serum Iron(12 weeks post study treatment)
- 6 Minute Walk Test: Distance Walked(12 weeks post study treatment)
- Stroke Volume (Cardiac Catheter)(12 weeks post treatment)
- Oxygen Consumption (VO2) at Metabolic Threshold(12 weeks post treatment)
- Peak Oxygen (O2) Pulse Rate(12 weeks post study treatment)
- Iron Indices: Transferrin Saturations(12 weeks post study treatment)
- Iron Indices: Soluble Transferrin Receptors (sTfR)(12 weeks post study treatment)
- Iron Indices: N-terminal Pro B-type Natriuretic Peptide (NT-pro-BNP)(12 weeks post study treatment)
- Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR Questionnaire): Symptom Score(12 weeks post study treatment)
- Cardiac Magnetic Resonance Imaging (MRI): Left Ventricular End Systolic Volume (LVESV)(12 weeks)
- Cardiac Magnetic Resonance Imaging (MRI): Right Ventricular Stroke Volume (RVSV)(12 weeks)
- Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR Questionnaire): QoL Score(12 weeks post study treatment)
- Oxygen Consumption (VO2) Level at Peak(12 weeks post study treatment)
- Cardiac Magnetic Resonance Imaging (MRI): Right Ventricular End Systolic Volume (RVESV)(12 weeks)
- Cardiac Magnetic Resonance Imaging: Left Ventricular Mass(12 weeks)
- Cardiac Magnetic Resonance Imaging (MRI): Right Ventricular End-diastolic Volume(12 weeks)
- Cardiac Magnetic Resonance Imaging (MRI): Right Ventricular Ejection Fraction (RVEF)(12 weeks)
- Cardiac Magnetic Resonance Imaging (MRI): Left Ventricular End Diastolic Volume (LVEDV)(12 weeks)
- Cardiac Magnetic Resonance Imaging: Left Ventricular Stroke Volume (LVSV)(12 weeks)
- Cardiac Magnetic Resonance Imaging (MRI): Left Ventricular Ejection Fraction (LVEF)(12 weeks)