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

Heart Failure Clinical Trial

— FAIR-HFpEF  

Official title:

Effect of IV Iron (Ferric Carboxymaltose, Ferinject) on Exercise Tolerance, Symptoms and Quality of Life in Patients With Heart Failure With Preserved Ejection Fraction (HFpEF) and Iron Deficiency With and Without Anaemia.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03074591
• Other study ID #: Charite
• Status: Completed
• Phase: Phase 4
• Start date: August 1, 2017
• Est. completion date: April 10, 2024

Study information

• Verified date: May 2024
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 10, 2024
• Est. primary completion date: December 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Heart Failure
• Iron-deficiency

Intervention

Drug:
• 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.
• Saline Solution for Injection
In the placebo/saline group, patients will receive the aequivalent number of normal saline infusions.

Locations

Country	Name	City	State
Germany	Charité University Medicine Berlin	Berlin
Germany	Herzzentrum Dresden GmbH	Dresden	Saxonia
Germany	University Medical Center Göttingen	Gottingen	Lower Saxony
Germany	Universitäres Herzzentrum Hamburg	Hamburg
Germany	Saarland University Medical Center	Homburg	Saarland
Germany	Innere Medizin/Kardiologie	Nurnberg	Bavaria
Germany	Herzklinik Ulm	Ulm

Sponsors (2)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	University of Göttingen

Country where clinical trial is conducted

Germany, 

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	exercise capacity	The difference of 6-minute walking distance in meters from baseline to week 24 in symptomatic patients with HFpEF with documented ID compared to the control group.	24 weeks
Secondary	6min-walking distance	Difference in 6-minute walking distance in meters from baseline to end of study in symptomatic patients with HFpEF with documented ID compared to the control group	52 weeks
Secondary	Patient Global Assessment (PGA)	Difference in Patient Global Assessment (PGA) in symptomatic patients with HFpEF with documented ID from baseline to end of study.; (7-point Likert scale [non-parametric])	52 weeks
Secondary	NYHA functional class	Difference in NYHA class from baseline to end of study in symptomatic patients with HFpEF	52 weeks
Secondary	Change in quality of life assessments	Difference in quality of life assessments (EQ-5D (= European Quality of Life 5 Dimensions 3 Level Version; = tool for Patient-Reported Outcomes (PRO) measurement); KCCQ (= Kansas City Cardiomyopathy Questionnaire)) from baseline to end of study in symptomatic patients with HFpEF.; KCCQ: (0-100) -> 100=best; EQ-5D (5-point Likert scale, 5 dimensions (mobility, self-care, usual activities, pain, anxiety) 5 levels (1 = no problems level 5 = extreme problems))	52 weeks
Secondary	Rate of recurrent heart failure hospitalisations and death	Difference in the rate of recurrent heart failure hospitalisations and deaths in symptomatic patients with HFpEF and ID.	52 weeks

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