Effect of IV Iron in Patients With Heart Failure With Preserved Ejection Fraction

NCT ID: NCT03074591

Last Updated: 2024-05-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-01
• Study Completion Date: 2024-04-10

Brief Summary

This study addresses, whether treatment with IV iron for patients with heart failure with preserved ejection fraction (HFpEF) and iron deficiency (ID), both with or without anaemia, can improve exercise capacity as measured by 6-minute walking test (6-MWT) and symptoms while being safe

Detailed Description

All previous trials have excluded patients with HFpEF. This study addresses, whether treatment with IV iron for patients with heart failure with preserved ejection fraction (HFpEF) and iron deficiency (ID), both with or without anaemia, can improve exercise capacity as measured by 6-minute walking test (6-MWT) and symptoms while being safe. The FAIR-HFpEF study was designed to evaluate the efficacy of Ferinject® in improving symptoms of HFpEF in patients with ID. Analyses will focus both on subjective and objective measures as well as on patients with and without anaemia. Furthermore, the tolerability and safety of Ferinject® treatment will be evaluated.

Conditions

Iron-deficiency; Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Treatment

Active treatment: Ferric Carboxymaltose solution (Ferinject®) for parenteral application, 50 mg/mL iron. Medication will be given as a short time infusion over 15 minutes in 100mL NaCl.

Group Type: ACTIVE_COMPARATOR

Ferric Carboxymaltose 50Mg/Ml Inj 15Ml

Intervention Type: DRUG

After baseline assessments patients will be randomised in a 1:1 ratio to receive Ferric Carboxymaltose IV or placebo/saline (normal saline: 0.9% w/v NaCl). In the Treatment group, Ferric Carboxymaltose will be administered according to the dosing schedule.

Placebo

Placebo: Normal saline (0.9% weight/volume (w/v) NaCl) administered in analogy to active treatment procedures.

Group Type: PLACEBO_COMPARATOR

Saline Solution for Injection

Intervention Type: DRUG

In the placebo/saline group, patients will receive the aequivalent number of normal saline infusions.

Interventions

Ferric Carboxymaltose 50Mg/Ml Inj 15Ml

After baseline assessments patients will be randomised in a 1:1 ratio to receive Ferric Carboxymaltose IV or placebo/saline (normal saline: 0.9% w/v NaCl). In the Treatment group, Ferric Carboxymaltose will be administered according to the dosing schedule.

Intervention Type: DRUG

Saline Solution for Injection

In the placebo/saline group, patients will receive the aequivalent number of normal saline infusions.

Intervention Type: DRUG

Other Intervention Names

Ferric Carboxymaltose; Saline Solution

Eligibility Criteria

Inclusion Criteria

1. Patient is willing to participate and provides written informed consent;

2. Age ≥18 years;

3. Clinical diagnosis of heart failure with preserved ejection fraction (HFpEF) with LVEF ≥45% at screening or within 6 months prior to planned randomisation (assessed by echocardiography or MRI);

4. Ambulatory for at least 7 days with NYHA class II or III at time of randomisation (the screening visit can take place at the end of a hospitalisation);

5. Treated with a diuretic;

6. Presence of atrial fibrillation (AF) at screening or randomisation is allowed in 2 out of 4 patients (calculated per centre);

7. At screening or randomisation, presence of one of the following criteria:

1. hospitalisation with a diagnosis of HF within 12 months prior to planned randomisation; OR

2. raised plasma levels of natriuretic peptides in a patient with sinus rhythm (i.e. in patients without AF: NT-proBNP >300 pg/mL or BNP >100 pg/mL or MR-proANP >120 pmol/L; in patients with AF: NT-proBNP >600 pg/mL or BNP >200 pg/mL or MR-proANP >250 pmol/l)

8. Evidence of diastolic dysfunction at screening or randomisation, defined as:

1. E/E' >13; OR

2. LA width ≥38 mm; OR

3. LA length ≥50 mm; OR

4. LA area ≥20 cm2; OR

5. LA volume ≥55 ml; OR

6. left atrial volume index >28 mL/m2;

9. Haemoglobin >9.0 g/dL and ≤14.0 g/dL (at screening);

10. ID with ferritin <100 ng/mL or ferritin 100-299 plus TSAT <20% (at screening);

11. 6-minute-walking distance at baseline <450 m (average of the last 2 documented tests within 8 weeks prior to planned randomisation that also need to be within 20% of each other).

Exclusion Criteria

1. Unable to sign informed consent

2. Any prior echocardiography measurement of LVEF <40%;

3. Clinical signs and symptoms of infection including fever >38°C;

4. Use of IV iron, erythropoietin or blood transfusions within the previous 60 days;

5. Use of concurrent immunosuppressive therapy;

6. History of acquired iron overload or haemochromatosis (or a first relative with haemochromatosis);

7. Known hypersensitivity to FCM or any other IV iron product;

8. Known bleeding or haemolytic anemia;

9. Presence of any condition that precludes exercise testing, such as decompensated HF, significant musculoskeletal disease, unstable angina pectoris, obstructive cardiomyopathy, severe uncorrected valvular disease, or uncontrolled brady-arrhythmias or tachy-arrhythmias;

10. Probable alternative diagnoses that in the opiniton of the investigator could account for the patient's HF symptoms such as severe obesity, primary pulmonary hypertension, or chronic obstructive pulmonary disease (COPD); hence, patients with the following are excluded:

1. Severe COPD, i.e. with known FEV1 <50%, requiring home oxygen therapy, or on chronic oral steroid therapy;

2. body mass index ≥40.0 kg/m2;

11. Presence of uncontrolled atrial fibrillation with resting heart rate >110/min;

12. Presence of uncontrolled hypertension with blood pressure >160/100 mm Hg;

13. Renal replacement therapy;

14. Concurrent therapy with an erythropoiesis stimulating agent;

15. Known active malignancy;

16. Known HIV or active hepatitis infection;

17. Pregnancy;

18. Patients, who may be dependent on the sponsor, the investigator or the trial sites, have to be excluded from the trial

19. Lack of willingness to storage and disclosure of pseudonymous disease data in the context of the clinical trial.

20. Participation in another clinical trial within previous 30 days and/ or anticipated participation in another trial during this study.

21. Inability to fully comprehend and/or perform study procedures in the investigator's opinion;

22. Persons staying at an institution due to order by a national body or a court of law.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Göttingen

OTHER

Sponsor Role: collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role: lead

Responsible Party

Prof. Stefan D Anker

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stefan Anker, Prof

Role: PRINCIPAL_INVESTIGATOR

Charite University, Berlin, Germany

Locations

Innere Medizin/Kardiologie

Nuremberg, Bavaria, Germany

University Medical Center Göttingen

Göttingen, Lower Saxony, Germany

Saarland University Medical Center

Homburg, Saarland, Germany

Herzzentrum Dresden GmbH

Dresden, Saxony, Germany

Charité University Medicine Berlin

Berlin, , Germany

Universitäres Herzzentrum Hamburg

Hamburg, , Germany

Herzklinik Ulm

Ulm, , Germany

Countries

Germany

References

von Haehling S, Doehner W, Evertz R, Garfias-Veitl T, Diek M, Karakas M, Birkemeyer R, Fillippatos G, Ponikowski P, Böhm M, Friede T, Anker SD. Iron deficiency in heart failure with preserved ejecton fracton: ratonale and design of the FAIR-HFpEF trial. Global Cardiol 2023; 1: 39-46.

Reference Type: BACKGROUND

Related Links

https://www.globalcardiology.info/site/article/view/15

Related Info

Other Identifiers

Charite

Identifier Type: -

Identifier Source: org_study_id