None listed
Conditions
Brief summary
The study aims to determine the efficacy and safety of iron supplementation in patients with atrial fibrillation and iron deficiency. Participants will be individuals with symptomatic atrial fibrillation who meet the inclusion and exclusion criteria. After providing consent, patients will have a blood tests to identify those with iron deficiency. Those with iron deficiency will continue their involvement in the study and will be asked to complete a set of health questionnaires, and undergo a cardiac ultrasound, exercise testing, and heart rhythm monitoring. Participants will be randomised to one of two treatment groups (in a 1:1 ratio) of either placebo or ferric carboxymaltose (iron) delivered through an infusion over 15 minutes. Patients will have follow-up visits at week 4 and 8, and will undergo final testing at week 12. The trial will recruit 84 patients. It is expected that participants who receive the supplementation of iron will improve their exercise tolerance after 12 weeks compared to those who receive the placebo.
Interventions
A total of 84 individuals will be randomised in a 1:1 ratio to ferric carboxymaltose or placebo.
Active Treatment
Ferric carboxymaltose (FCM, Ferinject ®, Vifor Pharma Pty Limited [Melbourne, Australia]), delivered intravenously over 15 minutes given as a single infusion during each visit at week 0, 1 (if required), 4, and 8.
Iron Repletion
For participants in the active treatment group, the total dose of FCM for repletion will be calculated using the Ganzoni formula, rounded to the nearest 10
A total of 84 individuals will be randomised in a 1:1 ratio to ferric carboxymaltose or placebo. Active Treatment Ferric carboxymaltose (FCM, Ferinject ®, Vifor Pharma Pty Limited [Melbourne, Australia]), delivered intravenously over 15 minutes given as a single infusion during each visit at week 0, 1 (if required), 4, and 8. Iron Repletion For participants in the active treatment group, the total dose of FCM for repletion will be calculated using the Ganzoni formula, rounded to the nearest 100mg. Participants in the active treatment group will receive FCM up to the calculated iron deficit, given over two infusions. The first infusion, given in week 0, will be up to a maximum dose of 1000 mg. The second infusion, given in week 1, will deliver the remainder of the required repletion dose, if required. Patients will be observed during the infusion, and for 30 minutes after its completion. They will have their vital signs taken before the infusion, 5 minutes after the commencement of the infusion, and upon conclusion of the infusion. Iron Maintenance At the start of weeks 4 and 8, participants will have iron studies performed. The results of these studies will be reviewed and entered into the web database by an unblinded study coordinator not involved in assessments of efficacy or safety. Participants in the active treatment group will then receive two maintenance infusions of 200 mg FCM, the first during week at the end of week 4 and the second at the end of week 8. In cases of elevated levels of ferritin > 800 ng/L, or ferritin > 500 ng/L when Tsat > 50% or Hb > 160 g/L detected on the iron studies performed the week prior, placebo is to be given instead of FCM during the respective visit. The primary outcome observed will be the change in VO2peak (mL/min/kg) from baseline to week 12, as measured by cycle ergometer cardiopulmonary exercise testing performed at baseline and week 12.
Sponsors
University of Adelaide
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• At least 18 years of age • Paroxysmal or persistent atrial fibrillation • Stable medical therapy in the 4 weeks prior to enrolment with no dose changes of atrial fibrillation drugs in the last 2 weeks • Haemoglobin < 150g/L • Serum ferritin < 100 ug/L or serum ferritin < 300 ug/L if Tsat < 20%
Exclusion criteria
• Known hypersensitivity to parenteral iron preparations • History of primary or secondary haemochromatosis • Known haemoglobinopathy or haemolytic anaemia • History of erythropoietin-stimulating agent, intravenous iron therapy, and / or blood transfusion in the 6 weeks prior to randomisation • Requiring treatment with blood transfusion in the next 3 months • Requiring surgery with anticipated moderate or severe blood loss in the next 3 months • Oral iron therapy at doses > 80 mg/day (of elemental iron) in the 1 week prior to randomisation (note: ongoing use of multivitamins containing <= 80 mg/day is permitted) • Planned cardioversion, catheter ablation, AV nodal ablation with pacemaker insertion or surgical ablation within the next 3 months • Body weight <= 35 kg • Exercise training program(s) in the 3 months prior to screening, or planned in the next 3 months • Ongoing blood loss • Current active autoimmune or systemic inflammatory diseases • Current active systemic infection or bacteraemia • Known chronic liver disease, hepatitis B or hepatitis C infection, or screening AST / ALT above three times the upper limit of normal range • Known active malignancy, with the exception of squamous cell and basal cell carcinoma of the skin, and cervical intraepithelial neoplasia • Currently receiving systemic chemotherapy and/or radiotherapy • Known chronic kidney disease • History of dialysis, current dialysis or dialysis planned within the next 3 months • Currently pregnant, breastfeeding, or trying to conceive within the next 3 months • Acute myocardial infarction, transient ischaemic attack, or stroke in the 3 months prior to randomisation • Coronary artery bypass graft, percutaneous intervention, or major surgery (including thoracic and cardiac surgery) within the last 3 months (diagnostic catheterisations are allowed) • Subject is unable to perform exercise testing, either according to the Investigator’s judgement, or due to the following conditions: o Severe lower limb musculoskeletal or neurological conditions o Unstable angina o Severe valvular or left ventricular outflow tract obstruction requiring intervention • Subject is currently enrolled in, or is within 30 days of completion of, another interventional study • Subject has previously been randomised to this study (subjects may be rescreened if they previously did not meet the eligibility criteria) • Subject will not be available for completion of all assessments as per the study protocol
Outcome results
None listed