Effects of Iron Therapy in Heart Failure With Preserved Ejection Fraction and Iron Deficiency (PREFER-HF)

NCT03833336 | Completed Phase 3 DMC

• 2 other identifiers: PREFER-HF2016-003604-31
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of the study is to evaluate whether the administration of iron to patients with heart failure and preserved ejection fraction results in an improvement of symptoms and functional class, in addition to evaluating whether oral iron is equivalent to intravenous iron to achieve this improvement.

Conditions

Heart Failure With Normal Ejection Fraction; Ferropenic Anemia

Keywords

heart failure; preserved ejection fraction; ferropenic anemia

Outcome Measures

Primary Outcomes (1)

• Six minute walking test distance

  Change in meters traveled in six minute walking test from baseline to week 24. An increase in distance is related to an improvement in functional capacity.

  24 weeks

Secondary Outcomes (4)

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

  24 weeks

• Quality of Life assesed by Kansas City Cardiomyopathy Questionnaire

  24 weeks

• Hospitalizations

  24 weeks

• Mortality

  24 weeks

Study Arms (4)

Placebo

PLACEBO COMPARATOR

normal saline solution plus oral lactose capsules

Other: Placebo

Intravenous ferric carboxymaltose

ACTIVE COMPARATOR

Ferric carboxymaltose 500-1000 mg at 0,6,12,24 weeks ( adjusted by protocol)

Drug: Ferric carboxymaltose

Oral iron A: ferroglycine sulfate

ACTIVE COMPARATOR

oral capsules of ferroglycine sulfate iron until week 24

Drug: Ferroglycine Sulfate

Oral iron B: sucrosomial iron

ACTIVE COMPARATOR

oral capsules of sucrosomial iron until week 24

Drug: Sucrosomial Iron

Interventions

Placebo OTHER

The group assigned to placebo will receive an infusion of normal saline solution plus oral lactose capsules identical to oral medication.

Placebo

Ferric carboxymaltose DRUG

The group assigned to receive intravenous iron will receive intravenous ferric carboxymaltose ajusted by weight and Hb levels according to study protocol plus oral placebo

Intravenous ferric carboxymaltose

Ferroglycine Sulfate DRUG

One group assigned to receive oral iron will receive two 100 mg oral capsule of ferroglycine sulfate plus intravenous placebo (normal saline solution)

Oral iron A: ferroglycine sulfate

Sucrosomial Iron DRUG

One group assigned to receive oral iron will receive or two oral capsule containing 30 mg of pyrophosphate sucrosomial iron plus intravenous placebo (normal saline solution)

Oral iron B: sucrosomial iron

Eligibility Criteria

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

You may qualify if:

• Subjects with stable chronic HF (NYHA II/IV functional class) on optimal background therapy (as determined by the investigator) for at least 4 weeks with no dose changes of heart failure drugs during the last 2 weeks (with the exception of diuretics). In general, optimal pharmacological treatment should include an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker and a beta blocker unless contraindicated or not tolerated and diuretic if indicated.
• Left ventricular ejection fraction \>45% (value within 3 months of planned date of randomization).
• BNP \>100 pg/mL and/or N-terminal-pro-BNP \>400 pg/mL at the screening visit.
• Subject must be capable of completing the 6 minute walking test
• Screening serum ferritin \<100 ng/mL or 100-300 ng/mL with transferrin saturation \<20%.
• At least 18 years of age.
• Before any study-specific procedure, the appropriate written informed consent must be obtained.

You may not qualify if:

• Subject has known sensitivity to any of the products to be administered during dosing.
• History of acquired iron overload.
• History of erythropoietin-stimulating agent, i.v. iron therapy, and/or blood transfusion in previous 6 weeks prior torandomization.
• Oral iron therapy at doses \>100 mg/day in previous 1 week prior to randomization. Note: ongoing use of multivitamins containing iron \<75 mg/day is permitted.
• Exercise training programme(s) in the 3 months prior to screening or planned in the next 6 months.
• Known active bacterial infection.
• Chronic liver disease (including active hepatitis) and/or screening alanine transaminase or aspartate transaminase above three times the upper limit of the normal range.
• Subjects with known hepatitis B surface antigen positivity and/or hepatitis C virus ribonucleic acid positivity.
• Subjects with known seropositivity to human immunodeficiency virus.
• Clinical evidence of current malignancy with exception of basal cell or squamous cell carcinoma of the skin, and cervical intraepithelial neoplasia.
• Currently receiving systemic chemotherapy and/or radiotherapy.
• Renal dialysis (previous, current, or planned within the next 6 months).
• Unstable angina pectoris as judged by the investigator; severe valvular or left ventricular outflow obstruction disease needing intervention; atrial fibrillation/flutter with a mean ventricular response rate at rest \>100 beats per minute.
• Acute myocardial infarction or acute coronary syndrome, transient ischemic attack, or stroke within the last 3 months prior to randomization.
• Coronary artery bypass graft, percutaneous intervention (e.g. cardiac, cerebrovascular, and aortic; diagnostic catheters are allowed), or major surgery, including thoracic and cardiac surgery, within the last 3 months prior to randomization.

Sponsors & Collaborators

• Institut de Recerca Biomèdica de Lleida: lead
• Fundació La Marató de TV3: collaborator

Study Sites (2)

Hospital Universitari Arnau de Vilanova

Lleida, Lleida, Spain

Location

Hospital de Manises

Manises, Valencia, Spain

Location

MeSH Terms

Conditions

Anemia, Iron-Deficiency; Heart Failure

Interventions

ferric carboxymaltose; ferroglycine sulfate; sucrosomial iron

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: José Luis Morales Rull, MD, PhD, Principal Investigator NUTRIMMIC group ( Nutrition Metabolism and Microbiota in Heart Failure)

Study Record Dates

• First Submitted: February 5, 2019
• First Posted: February 7, 2019
• Study Start: August 23, 2017
• Primary Completion: September 15, 2024
• Study Completion: December 20, 2024
• Last Updated: May 21, 2025

Record last verified: 2025-05

Locations

ES (2)