Oral Iron Therapy in Chronic Heart Failure Patients

Study Overview
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Brief Summary
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This study is design to evaluate the effectiveness of oral iron therapy in patients with heart failure and identify the central and peripheral mechanisms involved in the improvement of functional capacity after intervention. The investigation includes subjective and objective measures on exercise performance and heart function after intervention, and the tolerability of oral iron treatment.

Detailed Description
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This is a placebo-controlled, double-blind and randomized clinical trial that will include patients with symptomatic stable chronic heart failure (New York Heart Association Functional Class II or III), with diagnosis of iron deficiency (ferritin <100 ng / dL or ferritin between 100 - 300 ng / dL and transferrin saturation <20%) followed in an outpatient clinic. The enrolled patients (n = 36) will be randomly allocated in the ratio 2:1 to treatment with 60 mg of elemental iron orally (n = 24) or placebo administration (n = 12), 3 times daily for 4 months. The primary outcome investigated will be an increase of the transferrin saturation ≥ 10 percentage points between baseline and after the intervention. Secondary outcomes of the study will be the change in iron stores, red blood cell indices, neurohumoral activation, left ventricular systolic function, functional capacity, mechanoreflex activity, and quality life score.

Official Title
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Oral Iron Therapy in Chronic Heart Failure Patients: a Randomized, Placebo-controlled and Double-blind Clinical Trial (Pilot Study) of Efficiency

Conditions
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Heart Failure

Intervention / Treatment
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* Dietary Supplement: Ferrous sulfate
* Dietary Supplement: Placebo starch


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Both gender patients aged over 18 years; Diagnosis of chronic heart failure (identified by the use of Framingham criteria) for ≥ 6 months; New York Heart Association functional class II and III; Left ventricular ejection fraction ≤ 45% Regular attendance in an outpatient Heart Failure Clinic; Adequate therapeutic drug for heart failure syndrome based on beta-adrenergic blocker, angiotensin converting enzyme inhibitor or angiotensin receptor blocker, and mineralocorticoid receptor blocker; Evidence of iron deficiency in biochemical analyses: ferritin values < 100 ng/dL or between 100 ng/dL and 300 ng/dL, with transferrin saturation < 20%; Hemoglobin value between 9,0 - 16 g/dL; Provide written informed consent. Exclusion criteria Recent device implant (in the last 3 months) or perspective of device implantation (conventional or multisite pacing) in the next 6 months; Known active infection, inflammatory disease or C-reactive protein > 20 mg/dL Immunosuppressive therapy; In use of erythropoietin and/or current treatment with oral or intravenous iron; Clinically bleeding or blood transfusion in previous 3 months; Renal failure on dialysis; Hemoglobinopathies, hemochromatosis or active malignancy; Unstable angina pectoris or clinically significant uncorrected valvular disease, except mitral and tricuspid regurgitation secondary to ventricular dilatation; Acute myocardial infarction or acute coronary syndrome, transient ischaemic attack within the last 3 months; Uncontrolled arterial hypertension; Evidence of comorbidity that features active systemic disease, i.e. liver disease, collagen disease and untreated hyperthyroidism or hypothyroidism; Pregnant or lactating women; Anaemia due to reasons other than iron deﬁciency (i.e. vitamin B12 deficiency); Recent admission for decompensated heart failure (last 3 months).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ferrous sulfate<br> | Dietary Supplement: Ferrous sulfate<br>* 200mg of ferrous sulfate three times a day for 4 months<br>|
| Placebo Comparator: Placebo<br> | Dietary Supplement: Placebo starch<br>* 200mg of placebo starch three times a day for 4 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical parameter of serum transferrin saturation |  | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical parameter of hemoglobin in the hemogram analysis |  | 4 months | 
| Biochemical parameter of serum ferritin |  | 4 months | 
| Volume of oxygen consumed at peak exercise during cardiopulmonary exercise testing | Unit of measure mL/kg/min | 4 months | 
| Volume of oxygen consumed at anaerobic threshold during cardiopulmonary exercise testing | Unit of measure mL/kg/min | 4 months | 
| Ejection fraction of the left ventricle on doppler echocardiographic study | Unit of measure % | 4 months | 
| Biochemical parameter of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) serum levels |  | 4 months | 
| Blood pressure results during mechanoreflex evaluation | Unit of measure mmHg | 4 months | 
| Heart rate results during mechanoreflex evaluation | Unit of measure beats per minute | 4 months | 
| Volume of oxygen consumed results during mechanoreflex evaluation | Unit of measure mL/kg/min | 4 months | 
| Total score of physical, emotional, and overall dimensions domains of the Minnesota Living with Heart Failure Questionnaire | Score range 0 to 105 points | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure, Iron, Anemia, Chronic disease