Oral Iron Repletion Effects On Oxygen Uptake in Heart Failure
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 225
- 试验地点
- 17
- 主要终点
- Change in Peak VO2 (ml/Min) (VO2 =Oxygen Consumption)
研究概览
简要总结
The purpose of this study is to determine if oral iron (Fe) polysaccharide is superior to oral placebo in improving functional capacity as measured by change in peak VO2 (oxygen uptake) by CPET (Cardiopulmonary Exercise Testing) , of a broad population of patients with HFrEF (Heart Failure with Reduced Ejection Fraction) and Fe deficiency at 16 weeks.
Hypothesis: In a broad population of HFrEF patients with Fe deficiency, compared to oral placebo, therapy with oral Fe polysaccharide will be associated with improvement in functional capacity at 16 weeks as assessed by CPET.
详细描述
Therapeutic options to further improve functional capacity and symptoms in HF beyond neurohormonal antagonism are limited. Studies have demonstrated impaired oxidative capacity of skeletal muscle among HF patients, which may contribute to symptoms of breathlessness and persistent fatigue.
In addition to its role in erythropoiesis, iron (Fe) plays a critical role in skeletal muscle's oxygen (O2)-storage capacity (myoglobin) and systemic aerobic energy production. As Fe deficiency is common in patients with symptomatic HF, repletion of iron stores may improve submaximal exercise capacity among these patients beyond the effects on erythropoiesis.
While intravenous Fe repletion in HF patients with mild Fe-deficiency (i.e. Ferritin <100 or Ferritin 100-299 with transferrin saturation <20%) with or without anemia global well-being and functional status, oral Fe repletion has not been studied. Furthermore, the efficacy of oral Fe to replete iron stores in a similar population and its impact on functional capacity, measured objectively by peak VO2, remains unknown.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Age >18 years
- •Previous clinical diagnosis of heart failure with current New York Heart Association (NYHA) Class II-IV symptoms LVEF≤0.40 within 2 years prior to consent, and ≥3 months after a major change in cardiac status (i.e. CABG or CRT).
- •Serum ferritin between 15-100 ng/ml or serum ferritin between 100-299 ng/ml with transferrin saturation <20%
- •Hemoglobin 9.0-13.5 g/dL (males), 9-13.5 (females) at time of enrollment
- •Stable evidence-based medical therapy for HF (including beta-blocker and ACE-inhibitor/ARB unless previously deemed intolerant, and diuretics as necessary) with </= 100% change in dose for 30 days prior to randomization
- •a. Changes in diuretic dose guided by a patient-directed flexible dosing program are considered stable medical therapy
- •Willingness to provide informed consent
排除标准
- •Presence of a neuromuscular, orthopedic or other non-cardiac condition that prevents the patient from exercise testing on a bicycle/treadmill ergometer and/or inability to achieve an RER ≥ 1.0 on screening/baseline CPET
- •Severe renal dysfunction (eGFR< 20 ml/min/1.73m2)
- •Severe liver disease (ALT or AST > 3x normal, alkaline phosphatase or bilirubin >2x normal)
- •Gastrointestinal conditions known to impair Fe absorption (i.e. inflammatory bowel disease)
- •Known active infection as defined by current use of oral or intravenous antimicrobial agents
- •Documented active gastrointestinal bleeding
- •Active malignancy other than non-melanoma skin cancers
- •Anemia with known cause other than Fe deficiency or chronic disease
- •Fe overload disorders (i.e. hemochromatosis or hemosiderosis)
- •History of erythropoietin, IV or oral Fe therapy, or blood transfusion in previous 3 months.
- •Current ventricular assist device
- •Anticipated cardiac transplantation within the next 4 months
- •Primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy, acute myocarditis, constrictive pericarditis or tamponade
- •Previous adverse reaction to study drug or other oral Fe preparation
- •Known or anticipated pregnancy in the next 4 months
研究组 & 干预措施
Polysaccharide iron complex 150 mg
oral Fe polysaccharide 150mg twice daily for 16 weeks
干预措施: Polysaccharide Iron Complex 150 mg (Drug)
Placebo (for Polysaccharide Iron Complex 150 mg)
Oral placebo twice a day for 16 weeks
干预措施: Placebo (for Polysaccharide Iron Complex) (Drug)
结局指标
主要结局
Change in Peak VO2 (ml/Min) (VO2 =Oxygen Consumption)
时间窗: Baseline (BL) and Week 16
To determine if oral Fe (Iron) polysaccharide is superior to oral placebo in improving functional capacity as measured by change in peak VO2 by CPET (Cardiopulmonary Exercise Testing) , of a broad population of patients with HFrEF (Heart Failure with Reduced Ejection Fraction) and Fe deficiency at 16 weeks.
次要结局
- Change From Baseline in Sub-maximal Exercise Capacity as Assessed by the 6 Minute Walk Test (6MWT)(Measured at BL, week 8 and week 16)
- Change in Plasma NT-pro BNP(Measured at Baseline and Week 16)
- Change in Health Status: Kansas City Cardiomyopathy Questionnaire (KCCQ) - Clinical Summary Score(Measured at Baseline, Week 8 and Week 16)
- Change From Baseline in O2 Uptake Kinetics as Assessed by Mean Response Time From CPET(Measured at BL week 16)
- Change From Baseline in Ventilatory Efficiency Defined by Ve/VCO2(Measured at BL week 16)
研究者
Adrian Hernandez
MD, MHS, FAHA: Associate Professor of Medicine;Director, Outcomes & Health Services Research
Duke University