Effects of Iron Therapy and Exercise Training in Patients With Heart Failure and Iron Deficiency

Study Overview
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Brief Summary
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It is the aim of the study to prove, if intravenous supplementation with ferric carboxymaltose in iron-deficient patients with heart failure with reduced ejection fraction (HFrEF) leads to better exercise training effects compared to exercise training without previous iron supplementation.

Detailed Description
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In patients with heart failure with reduced ejection fraction (HFrEF) exercise training (ET) is recommended. In iron-deficient HFrEF patients iron supplementation by ferric carboxymaltose (FCM) is recommended. Both treatment options (ET and iron supplementation) affect oxidative metabolism. In this study iron-deficient HFrEF patients are included and randomly assigned to two study arms: Study arm A: Intravenous iron supplementation with FCM, subsequent (after 2 months) ET program. Study arm B: ET program, subsequent (after 2 months) intravenous iron supplementation with FCM. Primary study endpoint is exercise capacity (Peak VO2). Secondary endpoints are 6-minute walking distance, NYHA class, echocardiographic parameters and the combined endpoint cardiovascular hospitalizations and death.

Official Title
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A Randomized Trial on Sequential Effects of Iron Therapy and Exercise Training in Patients With Heart Failure and Iron Deficiency

Conditions
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Heart Failure With Reduced Ejection Fraction, Exercise Training, Ferric Carboxymaltose

Intervention / Treatment
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* Behavioral: Initial exercise training
* Drug: Initial FCM
* Drug: Subsequent FCM
* Behavioral: Subsequent exercise training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Heart failure with reduced ejection fraction ≤ 40% New York Heart Failure Asssociation class II-III Iron deficiency (ferritin < 100 ng/ml or 100-299 ng/ml, if transferrin saturation < 20%) Exclusion Criteria: Planned cardiovascular interventions (such as bypass surgery or valve interventions) Acute coronary Syndrome Malignant rhythm disturbances Acute or chronic infection Reduced prognosis or exercise capacity by non-cardiac comorbidities Missing informed consent

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Initial FCM<br>Intravenous iron supplementation with FCM, subsequent (after 2 months) exercise training program | Drug: Initial FCM<br>* Initial intravenous iron supplementation (FCM)<br>Behavioral: Subsequent exercise training<br>* Subsequent exercise training program after 2 months<br>|
| Experimental: Initial exercise<br>Exercise training program, subsequent (after 2 months) intravenous iron supplementation with FCM | Behavioral: Initial exercise training<br>* Initial exercise training program<br>Drug: Subsequent FCM<br>* Subsequent intravenous iron Supplementation (FCM) after 2 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise capacity (Peak VO2) | Peak VO2 is measured by spiroergometry | Change from baseline to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 Minute walking distance | To further assess exercise capacity | Change from baseline to 4 months | 
| New York Heart Association class (class I, II, III, IV with class I = best status, and class IV = worst status) | To assess symptoms | Improvement or deterioration of NYHA class from baseline to 4 months | 
| Echocardiographic ejection fraction of left ventricular function (measured in %, the lower the worse) | Systolic and diastolic function, chamber diameters, strain analyses | Improvement or deterioration of ejection fraction from baseline to 4 months | 
| Combined endpoint cardiovascular hospitalizations and death | To assess major events | After 2 and 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure with Reduced Ejection Fraction, Exercise Training Program, Iron Deficiency