Iron Substitution With Ferric Carboxymaltose as Treatment Strategy for Heart Failure Patients With Preserved Ejection Fraction

NCT05477498 | Withdrawn Phase 4 DMC

• 1 other identifier: 2018-02280
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to investigate the effects of treatment with intravenous ferric carboxymaltose on exercise tolerance measured as VO2peak in patients with HFpEF and iron deficiency, compared to placebo.

Conditions

Heart Failure With Normal Ejection Fraction; Iron-deficiency

Keywords

Exercise tolerance; iron substitution

Outcome Measures

Primary Outcomes (1)

• Change in peak oxygen uptake (VO2peak)

  Change of VO2peak will be measured by spiroergometry at the baseline and post-intervention visit.

  12 weeks

Secondary Outcomes (11)

• Change in ventriculo-arterial coupling (VAC)

  12 weeks

• Change in arteriovenous oxygen difference (Da-vO2)

  12 weeks

• Change in pulse wave velocity (PWV)

  12 weeks

• Change in New York Heart Association (NYHA) functional class

  12 weeks

• Change in habitual physical activity

  12 weeks

Study Arms (2)

Iron substitution

EXPERIMENTAL

Iron deficiency status will be assessed at the baseline visit (Day 0) as well as after 6 weeks of iron substitution (Week 6). The study drug will be given as FCM solution (Ferinject®, Vifor Pharma AG, Villars-sur-Glâne, Switzerland) by intravenous injection. Infusions of 10 or 20 mL (which is the amount of FCM that is equivalent to 500 or 1000 mg of iron, respectively) will be administered in ≥6 minutes diluted in ≈100 mL of sterile 0.9% sodium chloride solution (NaCl) for 10 mL, or in ≥15 minutes diluted in ≈200 mL for 20 mL. Dosing will be based on screening Hb level and weight, rather than on ferritin and TSAT results. On Day 0 (baseline visit), patients with Hb ≤14 g/dL, both \<70 kg and \>70 kg will receive 1000 mg FCM (20 mL), whereas patients with Hb \>14g/dL will receive 500 mg FCM (10 mL).

Drug: Ferric carboxymaltose

Placebo

PLACEBO COMPARATOR

Patients in the control group will receive a placebo solution administered as normal saline (0.9% weight/volume (w/v) NaCl) by intravenous injection as per the instructions for active treatment.

Drug: Placebo

Interventions

Ferric carboxymaltose DRUG

Application of FCM solution (Ferinject®, Vifor Pharma AG, Villars-sur-Glâne, Switzerland) by intravenous injection.

Also known as: Ferinject®

Iron substitution

Placebo DRUG

Application of placebo solution administered as normal saline (0.9% weight/volume (w/v) NaCl) by intravenous injection as per the instructions for active treatment.

Also known as: NaCl 0.9%

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent as documented by signature
• NYHA functional classes II-III
• Signs and symptoms of chronic HF, such as:
• Dyspnea
• Paroxysmal nocturnal dyspnea
• Reduced exercise tolerance
• Fatigue
• Extended recovery after exercising
• Peripheral edema (lower leg, ankle)
• EF (ejection fraction) \>50%
• Structural or functional changes in echocardiography:
• Left atrial volume index (LAVI) \>34 ml/m2 OR
• Left ventricular mass index (LVMI) \>115 g/m2 (men), \>95 g/m2 (women) OR
• E/E' (ratio between mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E')) \>13 AND mean E' septal and lateral wall \<9 cm/s
• NT-proBNP \>125 pg/ml

You may not qualify if:

• Age \<18 years
• Pregnancy or lactation
• Life-expectancy \<6 months
• Planned cardiac interventions in the following 6 months
• Unstable angina pectoris
• Uncontrolled brady- or tachyarrhythmia
• Severe uncorrected valvular heart disease
• Paroxysmal atrial fibrillation
• Clinically significant concomitant disease states (e.g. hypertension grades 2-3 (\>160/100 mmHg), severe renal failure (GFR \<30 ml/min/1.73m2), hepatic dysfunction (ALT or AST \>3x upper limit of normal, chronic obstructive pulmonary disease (COPD) grades III-IV)
• On-going cancer treatment
• Significant musculoskeletal disease limiting exercise tolerance
• Active infection
• Immunosuppressive medical therapy
• Earlier hypersensitivity to parenteral iron preparation
• Anemia and iron deficiency due to active and/or chronic bleeding

Sponsors & Collaborators

• Cantonal Hosptal, Baselland: lead
• Clinical Trial Unit, University Hospital Basel, Switzerland: collaborator

MeSH Terms

Conditions

Anemia, Iron-Deficiency

Interventions

ferric carboxymaltose; Sodium Chloride

Condition Hierarchy (Ancestors)

Anemia, Hypochromic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Thomas Dieterle, MD

  University Department of Internal Medicine, Cantonal Hospital Baselland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Each administration of the study drug will be carried out after completion of all applicable study related assessments. FCM is a dark brown solution and cannot be easily masked from placebo (0.9% saline). Therefore, unblinded study personnel (at least one study nurse) who will not be involved in any study procedures for efficacy or safety will be responsible for preparing the infusion and packing bag and tube in an opaque wrapping. Preparation and wrapping will take place in a different room to maintain subject blinding. Administration of the study drug will take place by blinded study personnel. The results of the central laboratory on iron deficiency status and Hb will be sent only to the unblinded study personnel, who will be responsible for evaluating these parameters for subsequent dosing and/or other intervention, if applicable.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Intervention group: Active treatment with ferric carboxymaltose, given as diluted solution by intravenous injection Control group: Placebo, administered as normal saline 0.9%

Study Record Dates

• First Submitted: July 5, 2019
• First Posted: July 28, 2022
• Study Start: December 1, 2021
• Primary Completion: August 31, 2022
• Study Completion: December 31, 2022
• Last Updated: July 28, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share