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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Exercise Training; Heart Failure With Reduced Ejection Fraction; Ferric Carboxymaltose
• Intervention / Treatment: Drug: Initial FCM; Behavioral: Subsequent exercise training; Behavioral: Initial exercise training; Drug: Subsequent FCM

Detailed Description

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.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Bremen, Germany
    • Bremer Institut für Herz- und Kreislaufforschung

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Herzzentrum Bremen

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): March 15, 2022
• Study Completion (Actual): March 15, 2022

Study Registration Dates

• First Submitted: January 8, 2019
• First Submitted That Met QC Criteria: January 10, 2019
• First Posted (Actual): January 14, 2019

Study Record Updates

• Last Update Posted (Actual): March 16, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Iron Deficiency; Heart Failure with Reduced Ejection Fraction; Exercise Training Program
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Heart Failure; Anemia, Iron-Deficiency
• Other Study ID Numbers: BIHKF-7162

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No