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Trial registered on ANZCTR


Registration number
ACTRN12615000952549
Ethics application status
Approved
Date submitted
31/08/2015
Date registered
10/09/2015
Date last updated
12/09/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Iron Infusion in Heart Failure Study
Scientific title
A Randomized Controlled Study of Ferric Carboxymaltose versus Placebo in Patients with Heart Failure on Short Term Outcomes including quality of life, exercise tolerance, hemodynamic indices, serum BNP and ST2 levels
Secondary ID [1] 286372 0
Nil
Universal Trial Number (UTN)
U1111-1168-4875
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Heart Failure 294513 0
Iron Deficiency 294514 0
Condition category
Condition code
Cardiovascular 294817 294817 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is 1000mg (20mL) of Ferric Carboyxmaltose, diluted in 250mL of 0.9% NaCl, administered intravenously via an intravenous cannula over 15 minutes as a once-off infusion.
Intervention code [1] 291436 0
Treatment: Drugs
Comparator / control treatment
The control group will be 250mL of normal saline (0.9% NaCl) administered intravenously over 15 minutes.
Control group
Placebo

Outcomes
Primary outcome [1] 294580 0
Change in Kansas City Cardiomyopathy Questionnaire score
Timepoint [1] 294580 0
2 weeks after infusion
Secondary outcome [1] 313651 0
Change in Patient Health Questionnaire - 9 score
Timepoint [1] 313651 0
2 weeks after infusion
Secondary outcome [2] 313652 0
Change in NT pro-BNP levels, collected in serum and measured by the electrochemiluminescence immunoassay "ECLIA" on the Elecsys immunoassay analyzer
Timepoint [2] 313652 0
2 weeks after infusion
Secondary outcome [3] 313653 0
Change in ST-2 levels, collected in serum and measured by enzyme-linked immunosorbant assay using the Critical Diagnositcs Presage ST2 assay kit
Timepoint [3] 313653 0
2 weeks after infusion
Secondary outcome [4] 313654 0
Changes in 6-minute walk test distance
Timepoint [4] 313654 0
1 day, 1 week, and 2 weeks after infusion
Secondary outcome [5] 313655 0
Changes in stroke volume measured noninvasively via impedance cardiography
Timepoint [5] 313655 0
1 day, 1 week, and 2 weeks after infusion
Secondary outcome [6] 313656 0
Changes in hand grip strength measured by a hand held dynamometer
Timepoint [6] 313656 0
1 day, 1 week, and 2 weeks after infusion
Secondary outcome [7] 317289 0
Changes in cardiac output measured noninvasively via impedance cardiography
Timepoint [7] 317289 0
1 day, 1 week, and 2 weeks after infusion
Secondary outcome [8] 317290 0
Changes in cardiac index measured noninvasively via impedance cardiography
Timepoint [8] 317290 0
1 day, 1 week, and 2 weeks

Eligibility
Key inclusion criteria
1) Chronic Heart Failure
2) Iron Deficiency
3) Patient willing and able to give consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Patients with a significant condition which will affect their clinical status such as terminal malignancy, HIV infection, etc
2) Pregnant patients
3) Patients unable to complete the Kansas City Cardiomyopathy Questionnaire, PHQ9 Questionnaire, or a 6-minute walk test
4) Patients that underwent a major change in clinical status including hospitalization or introduction of a new heart failure medication over the last month.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All patients are recruited from the Heart Failure Clinic at Concord Hospital. Patients with iron deficiency will be approached by the investigator regarding their interest in participation and informed consent will be obtained prior to their enrollment. Participating patients will present to the Concord Hospital Cardiovascular Outpatient department on the day of their infusion, where an independent clinical trial pharmacist will randomize the patient using a computer software program to iron or placebo. The investigators will not know which treatment is allocated to the patient
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
At randomization, the pharmacist will use a computer software to randomize the patient to either iron or placebo, stratified by their NYHA class (I vs II and III). The details on which treatment the patient received will be entered into a separate database that will not be made available to the investigators, ensuring they are blinded to what treatment the patients are having
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Ferric carboyxmaltose is easily distinguished from normal saline due to its distinctive brown color. To ensure blinding of the patient, the treatment is administered with a curtain shielding the patient's view. To ensure blinding of the investigators, the treatment is administered by an independent nurse not involved in data analysis.
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The primary outcome is an improvement in 2 week change in KCCQ score greater or equal to 5, which is considered a clinically significant change. Assuming a standard deviation of change in KCCQ of 8, a sample size of 82 patients (41 treatment, 41 placebo) will have 80% power to detect a between group change in KCCQ score of 5 or greater. We will also arrange for an outside statistician to conduct a blinded interim analysis after 20 patients per group have been enrolled to revise the sample size requirement and ensure that we have the power to show a clinically significant difference of 5 points between groups is statistically significant. We will analyze the outcomes with an ANCOVA model on the change in KCCQ score, PHQ-9 score, BNP, ST2 at 2 weeks. A repeated measures mix model will be used for changes in 6-minute walk test, hand grip strength, cardiac output, cardiac index, and stroke volume. We have pre-specified subgroups including NYHA class (I vs II/III), left ventricular ejection fraction (normal vs reduced), gender, anaemia (haemoglobin greater or equal to 12g/dL vs <12g/dL), diabetes, and estimated glomerular filtration rate (greater or equal to 60ml/min/1.73m2 vs <60 ml/min/1.73m2) for further analysis to identify interactions.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 3569 0
Concord Repatriation Hospital - Concord
Recruitment postcode(s) [1] 9383 0
2139 - Concord Repatriation Hospital

Funding & Sponsors
Funding source category [1] 290941 0
Hospital
Name [1] 290941 0
Concord Hospital Department of Cardiology Trust Fund
Address [1] 290941 0
Department of Cardiology
Concord Hospital
1A Hospital Road
Concord, NSW 2139
Country [1] 290941 0
Australia
Funding source category [2] 294507 0
Commercial sector/Industry
Name [2] 294507 0
Vifor Pharma
Address [2] 294507 0
Flughofstrasse 61
P.O. Box
CH-8152 Glattbrugg
Country [2] 294507 0
Switzerland
Primary sponsor type
Individual
Name
Professor Andrew Sindone
Address
Department of Cardiology
Concord Hospital
1A Hospital Road
Concord, NSW 2139
Country
Australia
Secondary sponsor category [1] 289626 0
Individual
Name [1] 289626 0
Dr. Christopher Chi-Yuen Wong
Address [1] 289626 0
Department of Cardiology
Concord Hospital
1A Hospital Road
Concord, NSW 2139
Country [1] 289626 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293420 0
Sydney Local Health District Human Research Ethics Committee - Concord Repatriation General Hospital
Ethics committee address [1] 293420 0
Building 20
Concord Repatriation General Hospital
Hospital Road
Concord NSW 2139
Ethics committee country [1] 293420 0
Australia
Date submitted for ethics approval [1] 293420 0
20/03/2015
Approval date [1] 293420 0
04/06/2015
Ethics approval number [1] 293420 0
HREC/15/CRGH/52

Summary
Brief summary
The purpose of our current study is to characterize the immediate short term impact of iron repletion on heart failure patients’ quality of life, exercise tolerance, hemodynamic indices, and serum BNP and ST2 levels; this will in turn add to the growing body of evidence supporting the investigation and treatment of iron deficiency in patients with congestive cardiac failure. Our hypothesis is that intravenous ferric carboxymaltose in congestive cardiac failure patients with concomitant iron deficiency will improve quality of life (as measured by the Kansas City Cardiomyopathy Questionnaire Score), short term exercise capacity (as measured on the six minute walk test), hemodynamic indices (as measured via impedance cardiography), and blood profile (BNP and ST2 levels )when compared with a placebo infusion of 0.9% sodium chloride.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 55854 0
Prof Andrew Sindone
Address 55854 0
Department of Cardiology
1A Hospital Road
Concord Hospital
Concord, NSW 2139
Country 55854 0
Australia
Phone 55854 0
+612 9767 6296
Fax 55854 0
Email 55854 0
Andrew.Sindone@email.cs.nsw.gov.au
Contact person for public queries
Name 55855 0
Dr Christopher Wong
Address 55855 0
Department of Cardiology
1A Hospital Road
Concord Hospital
Concord, NSW 2139
Country 55855 0
Australia
Phone 55855 0
+612 9767 6296
Fax 55855 0
Email 55855 0
christopher.c.wong@hotmail.com
Contact person for scientific queries
Name 55856 0
Prof Andrew Sindone
Address 55856 0
Department of Cardiology
1A Hospital Road
Concord Hospital
Concord, NSW 2139
Country 55856 0
Australia
Phone 55856 0
+612 9767 6296
Fax 55856 0
Email 55856 0
Andrew.Sindone@email.cs.nsw.gov.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary