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Trial registered on ANZCTR


Registration number
ACTRN12618000917235
Ethics application status
Approved
Date submitted
28/05/2018
Date registered
31/05/2018
Date last updated
6/11/2018
Date data sharing statement initially provided
6/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Correction of preoperative iron deficiency in children undergoing elective spinal fusion.
A Randomised control trial of Intravenous Iron vs. Oral Iron therapy.
Scientific title
Correction of preoperative iron deficiency in children undergoing elective spinal fusion.
A Randomised control trial of Intravenous Iron (Ferric Carboxymaltose) vs. Oral Iron therapy.
Secondary ID [1] 294699 0
Nil known
Universal Trial Number (UTN)
U1111-1212-7603
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Iron deficiency 307557 0
Anaemia 307558 0
Idiopathic Scoliosis 307559 0
Condition category
Condition code
Blood 306635 306635 0 0
Anaemia
Musculoskeletal 306636 306636 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients who are found to be iron deficient prior to their elective spinal surgery will be randomised to receive either oral or intravenous iron therapy preoperatively.

Those randomised to intravenous iron (intervention will receive a weight appropriate dose (see below) of ferric carboxymaltose administered as an intravenous infusion diluted in 0.9% Sodium Chloride as per manufactures guidelines. This dose will be administered once 3-5 weeks preoperatively unless the dose exceeds 20mg/kg or 1000mg in which case the patient will receive a divided dose timed one week apart.

Using the Ganzoni Formula to estimate total iron deficit:

Total iron dose (mg iron) = Weight(kg) x (Target Hb* - Actual Hb)(g/L) x 0.24 + Iron for stores**

Where:
* Target Hb <35kg = 130g/L
>35kg = 150g/L

** Iron for stores <35kg = 15mg/kg
>35kg = 500mg

The above calculated dose will be administered in the Medical Day Unit according to the CMI and manufactures guidelines.

Compliance and tolerably of intravenous iron will be documented directly in the patient medical notes.
Intervention code [1] 300990 0
Treatment: Drugs
Comparator / control treatment
For those patients randomised to oral iron therapy dosing is based on the AMH Children's Dosing Companion Guidelines:
1 month – 18 years, oral 3–6 mg/kg (maximum 200 mg) daily of elemental iron.
Patients may elect to take either ferrous sulphate liquid (6mg/mL) or ferrous fumigate tablets (67.5mg/tab) at a dose of 6mg/kg up to a maximum 200mg/day.

In consultation with the haematology department at the Women’s and Children’s Hospital the following doses of oral iron are suggested:
To increase tolerability and patient compliance, the iron supplementation will be started at half the recommended dose (3mg/kg/day) for 5 days.
Once drug tolerance is established (Day 6) the patient are will be instructed to increase to a full dose (6mg/kg/day – maximum 200mg elemental iron) to be taken until the day before surgery.
Control group
Active

Outcomes
Primary outcome [1] 305630 0
Incidence of severe anaemia as defined by a Haemoglobin concentration of <100g/L on full blood examination.
Timepoint [1] 305630 0
One week post operatively or at the time of discharge from hospital (whichever is earlier)
Secondary outcome [1] 345971 0
Incidence of blood transfusion as documented on the patient data sheets collected during their hospital admission and confirmed using the patient electronic record system (Oasis).
Timepoint [1] 345971 0
Time of discharge from hospital
Secondary outcome [2] 345972 0
Length of hospital stay (in days) as documented on the patient data sheets collected during their hospital admission and confirmed using the patient electronic record system (Oasis).
Timepoint [2] 345972 0
Time of discharge from hospital
Secondary outcome [3] 345973 0
Haemoglobin concentration as measured using full blood examination.
Timepoint [3] 345973 0
Once at the patients postoperative wound review appointment between 2 and 4 weeks postoperatively.
Secondary outcome [4] 347487 0
Incidence of anaemia as defined as a haemoglobin concentration <120g/L as measured using a full blood examination.
Timepoint [4] 347487 0
Once at the patients postoperative wound review appointment between 2 and 4 weeks postoperatively.
Secondary outcome [5] 347488 0
Haemoglobin concentration as measured using full blood examination.
Timepoint [5] 347488 0
Once at the patients postoperative review appointment between 6 and 12 weeks postoperatively.
Secondary outcome [6] 347489 0
Incidence of anaemia as defined as a haemoglobin concentration <120g/L as measured using a full blood examination.
Timepoint [6] 347489 0
Once at the patients postoperative review appointment between 6 and 12 weeks postoperatively.
Secondary outcome [7] 347490 0
Incidence of iron deficiency as definied by serum ferritin <30mcg/L on serum iron studies.
Timepoint [7] 347490 0
Once at the patients postoperative review appointment between 6 and 12 weeks postoperatively.
Secondary outcome [8] 347492 0
SRS 30 Questionnaire results. Patients will be asked to fill out a questionnaire and these results will be compared to their preoperative results.
Timepoint [8] 347492 0
Once at the preoperative planning appointment 6-12 weeks preoperatively and once at the postoperative review appointment between 6 and 12 weeks postoperatively.

Eligibility
Key inclusion criteria
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Age <18 years
- Diagnosed with adolescent idiopathic scoliosis
- Requiring posterior spinal fusion surgery of greater than or equal to 6 vertebral levels or other spinal fusion surgery associated with significant blood loss as determined by the surgical team
- Diagnosis of iron deficiency (ferritin <30mcg/L without anaemia or ferritin <100mcg/L with anaemia (Hb <120g/L))
- Ability to take oral medication and be willing to adhere to the oral iron regimen
- Willingness to attend hospital to undergo intravenous cannulation as required for the intravenous iron regimen
Agreement to adhere to Lifestyle Considerations throughout study duration
Minimum age
8 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

Current use of iron supplements
Pregnancy or lactation
Known allergic reactions to components of the IV ferric carboxymaltose or oral iron supplements
Significant medical co-morbidity such as neuromuscular disease, severe anaemia, cardiac disease, significant respiratory disease or impairment
Significant needle phobia
Hypophosphataemia, hypoparathyroidism, low vitamin D levels

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)
Opaque sealed envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated block randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
The null hypothesis states that there is no difference between oral and IV iron therapy in the incidence of severe anaemia at the time of discharge following elective spinal fusion surgery. The Primary Outcome measure is the Incidence of severe anaemia (Hb<100g/L) at discharge from hospital.
Previous audit of 16 spine patients demonstrated a mean discharge Hb of 96g/L, with a standard deviation of 15.2. Haematocrit was not recorded.
Intravenous iron sucrose has been proven to increase Hb in adults with iron deficiency anaemia of various aetiologies that is non-responsive to oral iron by up to 50% (85.4g/L to 121 g/L).
Whilst the figures for paediatric surgical patients’ responsiveness to IV iron are not known (hence the development of the proposed study); it has been postulated that this may be likely to be similar to adults. Thus these preexisting findings in adults allow for an extrapolation of data to enable power calculation for the proposed study. Namely, that of the of patients being discharged with severe anaemia (Hb<10 g/dL) after spinal surgery - which currently number 68% of patients - should be able to be halved (50% decrease) through judicious and appropriate IV iron therapy.
In view of the lack of previously defined population characteristics, power calculations have been done using:
a two study group design (Population rates of Discharge Hb<100 of 68.75% observed previously, compared to the expected post iron-infusion rates of Discharge Hb<100 of 34.38%, a figure chosen for reasons outlined above.)
Further, while data will be collected in a continuous manner, it will be analysed as dichotomous, binomial data (two outcomes only: Hb >10 g/dL or Hb <10g/dL.) to reduce the number of patients required for the study.
Assumption of alpha of 0.05, as per current medical research convention
Assumption of power (1-beta) of 0.8 as per current medical research convention
This will result in an expected sample size of approximately 14 patients in the treatment group.
This figure has been reached using the following equation, which was selected to meet the above criteria.. The calculation was performed using the on-line tool at http://clincalc.com/stats/samplesize.aspx.
This power calculation remains a guide, and will be subject to formal review by a statistician. Further recruitment may be required in the event of patient drop-out, the rates of which are difficult to predict. Anticipating a 10% attrition rate we will aim to recruit 32 patients (16 in each treatment arm).

Plan for statistical analysis will be further advised by a biostatistian prior to data being processed.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/12/2018
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
34
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 11003 0
Womens and Childrens Hospital - North Adelaide
Recruitment postcode(s) [1] 22794 0
5006 - North Adelaide

Funding & Sponsors
Funding source category [1] 299625 0
Hospital
Name [1] 299625 0
Women's and Children's Health Network
Country [1] 299625 0
Australia
Primary sponsor type
Individual
Name
Dr Rebecca Munk
Address
Department of Paediatric Anaesthesia
Woman's and Children's Hospital
72 King William Road
North Adelaide, South Australia
5006
Country
Australia
Secondary sponsor category [1] 298947 0
None
Name [1] 298947 0
Address [1] 298947 0
Country [1] 298947 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300214 0
Women's and Children's Health Network Human Research Ethics Committee
Ethics committee address [1] 300214 0
Ethics committee country [1] 300214 0
Australia
Date submitted for ethics approval [1] 300214 0
30/05/2018
Approval date [1] 300214 0
10/09/2018
Ethics approval number [1] 300214 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82938 0
Dr Rebecca Munk
Address 82938 0
Department of Paediatric Anaesthesia
Women's and Children's Hospital
72 King William Road
North Adelaide, South Australia, Australia
5006
Country 82938 0
Australia
Phone 82938 0
+618 8161 7231
Fax 82938 0
Email 82938 0
rebecca.munk@sa.gov.au
Contact person for public queries
Name 82939 0
Kory Horwood
Address 82939 0
Department of Orthopaedic Surgery
Women's and Children's Hospital
72 King William Road
North Adelaide, South Australia, Australia
5006
Country 82939 0
Australia
Phone 82939 0
+618 8161 7000
Fax 82939 0
Email 82939 0
kory.horwood@sa.gov.au
Contact person for scientific queries
Name 82940 0
Rebecca Munk
Address 82940 0
Department of Paediatric Anaesthesia
Women's and Children's Hospital
72 King William Road
North Adelaide, South Australia, Australia
5006
Country 82940 0
Australia
Phone 82940 0
+618 8161 7231
Fax 82940 0
Email 82940 0
rebecca.munk@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Patient blood results, length of stay and dose of iron received
When will data be available (start and end dates)?
After trial is completed for 5 years post completion.
Available to whom?
Other researchers or clinicians
Available for what types of analyses?
Meta-analysis
How or where can data be obtained?
By contacting the principle investigator


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
No additional documents have been identified.