Intravenous Iron Supplement for Iron Deficiency in Patients With Severe Aortic Stenosis

NCT04206228 | Completed Phase 2 Results

• 1 other identifier: 2019-002037-11
• Study Type: interventional
• Target: 149
• Locations: 1 country
• Sites: 1

Brief Summary

Iron deficiency is a prevalent nutritional deficiency and a common cause of anemia. Although iron deficiency is traditionally linked to anemia, iron deficiency is prevalent even in the absence of anaemia and in itself limits function and survival. Iron deficiency is a common feature of various chronic diseases, and up to 50% of patients with heart failure have iron deficiency. Iron deficiency is more prevalent the more advanced the disease is and occurs more frequently in women. Iron deficiency comprises absolute iron deficiency (usually defined as ferritin \< 100 ng/ml) as well as functional iron deficiency, in which iron supply is inadequate to meet the demand for the production of red blood cells and other cellular functions despite normal or abundant body iron stores. Iron deficiency is associated with poor exercise capacity, lethargy and reduced quality of life. Results from our studies have shown that iron deficiency is prevalent in patients with aortic stenosis. Some of the symptoms associated with aortic stenosis, such as fatigue, reduced exercise capacity, dyspnoea and cognitive dysfunction, have traditionally been thought to be caused by the haemodynamic derangements precipitated by the valvular stenosis. However, similar symptoms can be brought about by iron deficiency, and the investigators hypothesize that intravenous iron supplement will improve exercise capacity, muscle strength, cognition, health-related quality of life and myocardial function in patients with severe aortic stenosis and iron deficiency. This is a phase 2, double blind, randomised, placebo-controlled trial. Participants will be randomised in a 1:1 fashion to receive a single intravenous dose of iron isomaltoside (50 patients) or matching placebo (50 patients). The study is designed to show superiority with regard to the primary endpoint in patients assigned to active treatment versus patients allocated to the placebo arm. The main goal is to evaluate the effect of a single dose of intravenous iron isomaltoside on exercise capacity after transcatheter aortic valve implantation in patients with severe aortic stenosis and iron deficiency. For this study, the investigators have defined as serum ferritin \< 100 µg/l or ferritin between 100 and 300 µg/l in combination with a transferrin saturation \< 20 %.

Conditions

Severe Aortic Stenosis; Iron-deficiency

Keywords

Severe Aortic Stenosis; Iron-deficiency; Iron Isomaltoside; Exercise Capacity

Outcome Measures

Primary Outcomes (1)

• Submaximal Exercise Test

  The distance walked on a 6 min walk test performed 6 months after the trial intervention.

  6 months

Secondary Outcomes (9)

• Iron Deficiency

  6 months

• Muscle Strength

  6 months

• The 36-item Short Health Survey Questionnaire (SF-36) Summary PCS

  6 months

• The 3-level Version of EQ-5D (EQ-5D-3L) Questionnaire

  6 months

• EuroQol-visual Analogue Scales (EQ-VAS)

  6 months

Other Outcomes (1)

• Adverse Events

  6 months

Study Arms (2)

Active treatment

ACTIVE COMPARATOR

Active drug: Intravenous iron isomaltoside dissolved in 100 ml NaCl 0.9 %

Drug: Intravenous iron isomaltoside

Placebo

PLACEBO COMPARATOR

Placebo: Intravenous NaCl 0.9 % dissolved in 100 ml

Drug: Placebo

Interventions

Intravenous iron isomaltoside DRUG

The active drug, iron isomaltoside, will be administered as a single, intravenous infusion of 20 mg/kg body weight (rounded off to the nearest 100 mg) dissolved in 100 ml NaCl as recommended by the drug manufacturer ("on-label" treatment), over 30 minutes only (1,67 ml/min).

Also known as: Monofer®

Active treatment

Placebo DRUG

The placebo will be prepared according to the randomisation code, and administered as a single intravenous infusion over 30 minutes only (1,67 ml/min).

Also known as: Intravenous sodium chloride 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:

• Aortic stenosis patients with peak flow velocity (\>3.5 m/s) scheduled for aortic valve replacement with TAVI
• Iron deficiency defined as serum ferritin \< 100 µg/l or ferritin between 100 and 300 µg/l in combination with a transferrin saturation \< 20 %.
• Age \> 18 years.
• Signed informed consent and expected compliance with protocol.

You may not qualify if:

• Patients will be excluded from the study if they meet any of the following criteria:
• Anaemia (Haemoglobin \< 100 mg/l)
• Haemochromatosis
• Haemosiderosis
• Porphyria cutanea tarda
• Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells
• Decompensated liver disease (Child-Pugh score 7 or higher)
• End-stage renal failure, i.e. eGFR \< 15 ml/min or on renal replacement therapy
• Planned major surgery within 6 months
• Unresolved cancer predisposing to chronic bleeding or associated with life expectancy \< 2 years
• On erythropoietin analogues
• Known sensitivity or intolerance to iron isomaltoside or other parenteral iron preparations
• A clear indication for intravenous iron supplement
• On oral iron substitution (unless the subject agrees to stop treatment prior to randomisation)
• Alcohol or drug abuse within 3 months of informed consent that would interfere with trial participation or any ongoing condition leading to decreased compliance with study procedures or study drug intake

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (1)

Rikshospitalet University Hospital

Oslo, Norway

Location

Related Publications (2)

• Bardan S, Kvaslerud AB, Andresen K, Klove SF, Edvardsen T, Gullestad L, Broch K. Intravenous ferric derisomaltose in iron-deficient patients undergoing transcatheter aortic valve implantation due to severe aortic stenosis: study protocol of the randomised controlled IIISAS trial. BMJ Open. 2022 Sep 2;12(9):e059546. doi: 10.1136/bmjopen-2021-059546.

  PMID: 36691165 DERIVED

• Kvaslerud AB, Bardan S, Andresen K, Klove SF, Fagerland MW, Edvardsen T, Gullestad L, Broch K. Intravenous iron supplement for iron deficiency in patients with severe aortic stenosis scheduled for transcatheter aortic valve implantation: results of the IIISAS randomised trial. Eur J Heart Fail. 2022 Jul;24(7):1269-1279. doi: 10.1002/ejhf.2557. Epub 2022 Jun 3.

  PMID: 35579454 DERIVED

MeSH Terms

Conditions

Aortic Valve Stenosis; Anemia, Iron-Deficiency

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction; Anemia, Hypochromic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Kaspar Broch
• Organization: Oslo University Hospital

sbbrok@ous-hf.no

+4723 07 00 00

Study Officials

• Lars Gullestad, MD, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 18, 2019
• First Posted: December 20, 2019
• Study Start: January 13, 2020
• Primary Completion: February 15, 2022
• Study Completion: February 15, 2022
• Last Updated: April 15, 2026
• Results First Posted: April 15, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)