The Iron and Muscle Study

NCT04862715 | Completed Phase 4 DMC

• 1 other identifier: 234820
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-center randomized controlled trial that will examine the efficacy of IV iron supplementation when compared to placebo, with and without exercise training, on changes in patient exercise capacity. The study aims to provide sufficient data to inform a power calculation for the definitive study to examine whether IV iron therapy in patients with CKD stages 3-4 (non-dialysis) can improve exercise capacity, muscle metabolism and physical function. Specifically, we propose to examine whether a strategy of IV iron therapy in patients with stages 3-4 CKD who are iron-deficient but NOT anaemic leads to improvements in exercise capacity. Very little is currently known about the effects of iron deficiency on cardiac or skeletal muscle metabolism in patients suffering from CKD. Nevertheless, it seems likely that iron deficiency will contribute to mitochondrial dysfunction and reduced energy production in cardiac or skeletal muscle of CKD patients, and importantly may contribute to the reduced exercise capacity, physical function and overwhelming fatigue commonly reported in this population. The results of this trial will provide data to ascertain whether intravenous iron therapy might be beneficial to exercise capacity, muscle metabolism, physical function, and fatigue and whether iron repletion enhances the effect of an exercise intervention.

Conditions

CKD Stage 3; CKD Stage 4; Iron-deficiency

Outcome Measures

Primary Outcomes (1)

• Exercise capacity as measured by 6 minute walk distance (6MWD)

  An exercise capacity test

  4 weeks

Secondary Outcomes (13)

• Haemoglobin levels

  12 weeks

• Iron status

  12 weeks

• Renal function

  12 weeks

• VO2 peak test (in a sub-set of participants)

  12 weeks

• Isokinetic dynamometry (muscle strength)

  12 weeks

Study Arms (2)

Treatment

ACTIVE COMPARATOR

Active study medication Medication name: Ferinject® Active ingredient: Ferric carboxymaltose Dosage form: 50 mg iron/ml solution for injection/infusion. Appearance: Dark brown, non-transparent aqueous solution Excipients: Sodium hydroxide, hydrochloric acid and water for injection Strength/Packaging: Each 2 ml vial contains 100 mg of iron as ferric carboxymaltose. Each 10 ml vial contains 500 mg of iron as ferric carboxymaltose. Each 20 ml vial contains 1,000 mg of iron as ferric carboxymaltose. Manufacturer: Vifor Pharma UK Limited

Drug: Ferinject

Placebo

PLACEBO COMPARATOR

Medication name: NaCl (sodium chloride 0.9%) Active ingredient: NaCl (sodium chloride 0.9%) Dosage form: 0.9% w/v NaCl as sterile solution in water for injection Excipients: Water Strength/Packaging: 100 ml container with 100 ml normal saline Manufacturer: As per local hospital supplier

Other: Placebo: NaCl (sodium chloride 0.9%)

Interventions

Ferinject DRUG

Active study medication Medication name: Ferinject® Active ingredient: Ferric carboxymaltose Dosage form: 50 mg iron/ml solution for injection/infusion. Appearance: Dark brown, non-transparent aqueous solution Excipients: Sodium hydroxide, hydrochloric acid and water for injection Strength/Packaging: Each 2 ml vial contains 100 mg of iron as ferric carboxymaltose. Each 10 ml vial contains 500 mg of iron as ferric carboxymaltose. Each 20 ml vial contains 1,000 mg of iron as ferric carboxymaltose. Manufacturer: Vifor Pharma UK Limited

Treatment

Placebo: NaCl (sodium chloride 0.9%) OTHER

Medication name: NaCl (sodium chloride 0.9%) Active ingredient: NaCl (sodium chloride 0.9%) Dosage form: 0.9% w/v NaCl as sterile solution in water for injection Excipients: Water Strength/Packaging: 100 ml container with 100 ml normal saline Manufacturer: As per local hospital supplier

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with established CKD (Stages 3-4) not on dialysis
• Resting BP ≤ 160/95mmHg
• Men and women aged 18 - 80 years
• Serum ferritin level less than 100μg/L AND/OR transferrin saturation ≤20%
• Haemoglobin 110 - 150 g/L

You may not qualify if:

• Pregnancy or breast feeding (Female patients of childbearing age will be asked if there is any possibility they may be pregnant. This is standard of care and no pregnancy test will be requested unless there is doubt about this. IV iron is given to many pregnant patients in standard treatment and there is no evidence of harm to mother or foetus).
• Weight \< 50kg
• Known allergy to iron therapy
• Haemochromatosis, porphyria cutanea tarda or history of acquired iron overload
• Intravenous iron within previous 6 weeks
• CRP \> 50 mg/L
• Serum phosphate \< 0.7 mmol/L.
• Active infection
• Current therapy with ESAs
• Uncontrolled atrial fibrillation
• Use of anticoagulants in those under consideration for muscle biopsy
• Unstable angina or heart attack within the last year
• Presence of solid organ cancer
• Known haemoglobinopathy, myelodysplasia, or myeloma
• Patients with peripheral vascular or musculoskeletal disease, who the investigator deems unable to carry out the 6MWT.

Sponsors & Collaborators

• King's College Hospital NHS Trust: lead
• King's College London: collaborator
• University of Leicester: collaborator

Study Sites (1)

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

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

• Kate Bramham

  Kings College Hospital NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2019
• First Posted: April 28, 2021
• Study Start: April 26, 2019
• Primary Completion: December 21, 2021
• Study Completion: February 21, 2022
• Last Updated: March 2, 2022

Record last verified: 2022-02

Locations

GB (1)