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Trial registered on ANZCTR


Registration number
ACTRN12616001219471
Ethics application status
Approved
Date submitted
30/08/2016
Date registered
2/09/2016
Date last updated
31/01/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Iron infusion in iron-deficient patients undergoing surgery for colorectal cancer who are anaemic versus not anaemic in order to improve physical fitness as determined by exercise testing and a quality of life questionnaire.
Scientific title
An iron infusion with Ferric Carboxymaltose as a technique of improving physiological reserve in iron deficient patients undergoing surgery for colorectal cancer: a randomized control trial
Secondary ID [1] 290067 0
Nil known
Universal Trial Number (UTN)
Trial acronym
FeRIC (Fe dEficiency in ColoRectal Cancer)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 300129 0
Iron deficiency 300130 0
Anaemia 300131 0
Condition category
Condition code
Cancer 300008 300008 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Anaesthesiology 300009 300009 0 0
Other anaesthesiology
Blood 300010 300010 0 0
Anaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention will occur independent of date of surgery. The follow-up date will occur before date of surgery. Control treatment will occur independent of date of surgery. The follow-up date will occur before date of surgery. This means that FCM will be administered at least 2 weeks before any further intervention, such as neoadjuvant chemotherapy or surgery. This will not cause any delay in normal treatment.

After baseline CPX is performed (Day 0), participants will receive 1000mg of Ferric Carboxymaltose (FCM) in a maximum of 250mls of 0.9% saline solution; Ferinject, Vifor Pharma, Glattbrugg, Switzerland) over a 15 minute period. All patients will be monitored for 30 minutes following completion of the infusion. No further blood tests will be required on the day of the infusion.

Adherence to FCM will be monitored as the patient will be monitored on the ward.
Intervention code [1] 295795 0
Treatment: Drugs
Comparator / control treatment
Control treatment will occur independent of date of surgery. The follow-up date will occur before date of surgery. This means that the placebo will be administered at least 2 weeks before any further intervention, such as neoadjuvant chemotherapy or surgery. This will not cause any delay in normal treatment.

After baseline CPX is performed (Day 0), participants will receive 250mls of 0.9% saline solution as a placebo over a 15 minute period. All patients will be monitored for 30 minutes following completion of the infusion. No further blood tests will be required on the day of the infusion.

Adherence to the placebo will be monitored as the patient will be monitored on the ward.
Control group
Placebo

Outcomes
Primary outcome [1] 299495 0
To assess if the preoperative functional status (as measured by CPX) of anaemic and/or iron deficient colorectal cancer patients will be improved following an intravenous infusion of FCM. The primary endpoint is the change in VO2peak measured by the CPX, from baseline CPX (Day 0) to CPX test #2 (Day 14) following a transfusion of FCM.
Timepoint [1] 299495 0
The primary endpoint is the change in VO2peak measured by the CPX, from baseline CPX (Day 0) to CPX test #2 (Day 14) following a transfusion of FCM.
Secondary outcome [1] 327344 0
To assess if an infusion of Ferric Carboxymaltose (FCM) will improve Anaerobic Threshold (AT). Change in AT measured by the CPX, from baseline CPX (Day 0) to CPX test #2 (Day 14) following a transfusion of FCM (Day 0)
Timepoint [1] 327344 0
Change in AT measured by the CPX, from baseline CPX (Day 0) to CPX test #2 (Day 14) following a transfusion of FCM (Day 0)
Secondary outcome [2] 327345 0
To assess if an infusion of FCM will improve haemoglobin from baseline blood test (Day o) to second blood test (Day 14)
Timepoint [2] 327345 0
Change in haemoglobin from day of CPX #1 (Day 0) to day of CPX test #2 (Day 14)
Secondary outcome [3] 327346 0
To assess if an infusion of FCM will improve reticulocyte count from baseline blood test (Day o) to second blood test (Day 14)
Timepoint [3] 327346 0
Change in reticulocyte count from day of CPX #1 (Day 0) to day of CPX test #2 (Day 14)
Secondary outcome [4] 327361 0
To assess if an infusion of FCM will improve ferritin count from baseline blood test (Day o) to second blood test (Day 14)
Timepoint [4] 327361 0
Change in ferritin from day of CPX #1 (Day 0) to day of CPX test #2 (Day 14)
Secondary outcome [5] 327362 0
To assess if an infusion of FCM will improve transferrin saturations from baseline blood test (Day o) to second blood test (Day 14)
Timepoint [5] 327362 0
Change in transferrin saturations from day of CPX #1 (Day 0) to day of CPX test #2 (Day 14)
Secondary outcome [6] 327363 0
To assess if an infusion of Ferric Carboxymaltose will improve Health-Related Quality of Life indicators, from Day 0 to Day 14
Timepoint [6] 327363 0
Change in Health-Related Quality of Life outcomes from time of baseline CPX to time of CPX test #2 as measured by WHODAS-2 and EQ-5D from Day 0 to Day 14

Eligibility
Key inclusion criteria
1. Patients 18 years of age and older
2. Patients with histologically confirmed colorectal cancer presenting to Peter MacCallum Cancer Centre, or Epworth Hospital (Richmond and Eastern campuses).
3. Ferritin <100mcg/l or 100-300mcg/L and TSAT<20%
4. Normal Serum Vitamin B12 and Folate levels
5. Normal red cell folate and B12 levels
6. Patients planned for surgery colorectal surgery
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Hb (>130mg/dL male, or >120mg/dL female) & (either one of: Ferritin >300mcg/l, or Ferritin >100mcg/l and TSAT >20%)
2. Marked Iron deficiency anaemia precluding randomization: Hb < 110 mg/dL & Ferritin <20 mcg/l
3. Iron therapy contraindicated
4. Treatment with iron therapy or blood transfusion in the previous 12 weeks
5. Presentation for neoadjuvant CRT or Surgery within the study period
6. Patients with a known haematological abnormality (such as haemochromatosis or thalassemia, TSAT >50%)
7. Liver disease where ALT is above 3 times the upper limit of the normal range
8. Patients with a history of acquired iron overload or iron storage disorders
9. Previous hypersensitivity or allergic reactions to parentral (polymaltose/carboxymaltose) iron preparations
10. Patients unable to give informed consent
11. Physical disability preventing CPX, or contraindication in local CPX policy (such as angina at rest)
12. Patients included in other clinical trials that involve the administration of iron therapy
13. Blood transfusion in previous three months

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)
Treatment allocation will be concealed from the investigators involved in the CPX. Participants and investigators will be blinded to the study drug by using non-transparent bags and lines, which will be prepared by the Peter MacCallum pharmacy under supervision of a Clinical Trial Pharmacist.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated randomisation will be carried out using random permuted blocks of 6 within each Hb stratum. Patients will be stratified according to Hb levels (less than 120mg/dL female, less than 130mg/dL male vs greater than or equal 120mg/dL female, greater than or equal to 130mg/dL male). Once the planned allocation has been reached in either of the Hb strata, recruitment to that stratum will cease. Treatment allocation will be concealed from the investigators involved in the CPX. Participants and investigators will be blinded to the study drug by using non-transparent bags and lines, which will be prepared by the Peter MacCallum pharmacy under supervision of a Clinical Trial Pharmacist.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
A multivariate linear regression model will be built with i) baseline V02peak, ii) treatment arm (IV iron vs. control) and iii) anaemia status as independent variables, and change in V02 peak between CPX test #2 and baseline as the dependent variable (outcome variable). The model will be used to estimate the difference between treatment arms in the mean change in V02peak between baseline and CPX test #2, and its 95% CI.
The assumptions of the linear regression will be tested and a normalising transformation will be considered if necessary.

We assume a baseline average V02peak of 15mls/kg/min, with a standard deviation of 2mls/kg/min in each group (treatment and control). With a total sample size of 36 patients, the power to detect a treatment effect of 2.1mls/kg/min (i.e. an expected mean change in V02 peak between baseline and CPX2 of 2.1 in the treatment group vs. an expected change of zero in the placebo group), adjusted for unequal sampling (2:1) 82% (2 sided type 1 error rate = 5%). Patients who withdraw from the study prior to the CPX2 test will be replaced in order to ensure that the total planned sample size is achieved.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
20/09/2016
Actual
31/10/2016
Date of last participant enrolment
Anticipated
20/03/2020
Actual
Date of last data collection
Anticipated
20/07/2020
Actual
Sample size
Target
36
Accrual to date
3
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 6589 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 6590 0
Epworth Richmond - Richmond
Recruitment postcode(s) [1] 14196 0
3000 - Melbourne
Recruitment postcode(s) [2] 14197 0
3121 - Richmond

Funding & Sponsors
Funding source category [1] 294433 0
Charities/Societies/Foundations
Name [1] 294433 0
Peter MacCallum Cancer Centre Foundation Grant
Country [1] 294433 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
305 Grattan St
Melbourne
VIC 3000
Country
Australia
Secondary sponsor category [1] 293286 0
None
Name [1] 293286 0
Address [1] 293286 0
Country [1] 293286 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295861 0
Peter MacCallum Cancer Centre Ethics Committee
Ethics committee address [1] 295861 0
305 Grattan St,
Melbourne
VIC 3000
Ethics committee country [1] 295861 0
Australia
Date submitted for ethics approval [1] 295861 0
09/05/2016
Approval date [1] 295861 0
30/08/2016
Ethics approval number [1] 295861 0
HREC/16/PMCC/50

Summary
Brief summary
This pilot study aims to test if an iron infusion to iron-deficient patients planned for surgery for colorectal cancer who are anaemic versus not anaemic will improve physical fitness.

Who is it for?
You may be eligible to join this study if you are aged 18 years and above, have histologically confirmed colorectal cancer and Ferritin of less than 100mcg/l or between 100-300mcg/L with a transferrin saturation of less than %20.

Study details
Consenting participants will be randomly (by chance) allocated to either receive an infusion enriched with 1000mg iron (Ferric Carboxymaltose) or saline solution of similar appearance. All participants will receive maximum of 250mls of 0.9% saline solution with or without iron (depending on group) over a 15 minute period. All patients will be monitored for 30 minutes following completion of the infusion. No further blood tests will be required on the day of the infusion.

This project is a pilot study, and if feasible, may be extended to a larger study in the future. This project is being conducted at Peter MacCallum Cancer Centre and Epworth Health Care.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 68742 0
Mr Vladimir Bolshinsky
Address 68742 0
Division of Surgical Oncology
Peter MacCallum Cancer Centre
Locked Bag 1
A'Beckett St,
Melbourne
VIC 8006
Country 68742 0
Australia
Phone 68742 0
+61 3 8559 5000
Fax 68742 0
Email 68742 0
[email protected]
Contact person for public queries
Name 68743 0
Dr Michael Li
Address 68743 0
Department of Cancer Anaesthesia, Perioperative & Pain Medicine
Peter MacCallum Cancer Centre
Locked Bag 1
A'Beckett St,
Melbourne
VIC 8006
Country 68743 0
Australia
Phone 68743 0
+61 3 8559 5000
Fax 68743 0
Email 68743 0
[email protected]
Contact person for scientific queries
Name 68744 0
Mr Vladimir Bolshinsky
Address 68744 0
Division of Surgical Oncology
Peter MacCallum Cancer Centre
Locked Bag 1
A'Beckett St,
Melbourne
VIC 8006
Country 68744 0
Australia
Phone 68744 0
+61 3 8559 5000
Fax 68744 0
Email 68744 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
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