Pathophysiological relevance of IRON deficiency and related mitochondrial dysfunction in Heart Failure with Preserved Ejection Fraction (IRON-HFpEF)

Phase 1

Conditions: Heart failure with preserved ejection fraction
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2019-003461-17-NL

Lead Sponsor: Amsterdam UMC, location VUmc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 45

Inclusion Criteria

1. Diagnosis of heart failure with preserved ejection fraction
a. signs/and symptoms of heartfailure (NYHA II or higher)
b. Left ventricular ejection fraction =50%
c. evidence of left ventricular diastolic dysfunction:
-pulmonary capillary wedge pressure (PCWP) at rest = 15mmHg and/or PCWP during exercise = 25mmHg
or if no right heart catheterisation has been performed:
-HFpEf score = 6;
-diastolic dysfunction grade II or higher on echocardiogram + NTproBNP of >125 pg/mL
d. no other significant cardiac (e.g. significant valvular disease) or extra-cardiac con-dition (e.g. severe COPD) that explains symptoms
2. Optimal medical treatment
3. Clinically stable
4. Iron deficient (ferritin <100pg/L or ferritin 100-300pg/L and transferrin saturation or TSAT <20%).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

Exclusion Criteria

1. No informed consent
2. Contra indication ferric carboxy maltose
a. known allergic reaction to product; b. clinical signs of an acute infection; c. conditions with high risk for an allergic reaction (severe asthma or eczema, systemic lupus erhytematosus, rheumatoid arthtritis or concurrent use of significant immunosuppressive therapy); severe liver disease
3. History of (previous 2 months) or planned use of intravenous/oral iron, erythro-poietin or blood transfusion
4. Acute coronary syndrome, TIA/CVA, PCI/CABG/valve replacement or any major surgery within 3 months prior;
5. Unable to undergo the complete study protocol (i.e. right heart catheterisation, 6 minute walk distance)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Asses whether, in patients with heart failure with preserved ejection fraction and iron deficiency, ferric carboxymaltose improves left ventricular diastolic function and skeletal muscle function by improving energy metabolism;Secondary Objective: Whether ferric carboxymaltose corrects iron tissue in end-organs (heart and skeletal muscle);Primary end point(s): Exercise PCWP measured by right heart catheterisation (gold standard for evaluation of left ventricular diastology);Timepoint(s) of evaluation of this end point: 4 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Myocardial and calf muscle PCr/ATP-ratio at rest measured by 31P-MRS.<br>2. PCr/ATP ratio in calf muscle during exercise . And PCr recovery after exercise<br>3. Change in mitochondrial function<br>4. Correction of iron storage in plasma (ao ferritin and TSAT) and organs (MRI of heart / skeletal muscle)<br>5 Safety endpoints (SAE's)<br>6. Change in symptoms (NYHA, fatigue-score and quality of life questionairres (KCCQ and EQ-5D)<br>7. Change in exercise tolerance (6 minute walk test; bicycle ergometry)<br>8. Change in NTproBNP<br>9. Change in microvascular function (substudy);Timepoint(s) of evaluation of this end point: 4 months