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Trial registered on ANZCTR


Registration number
ACTRN12608000186358
Ethics application status
Approved
Date submitted
7/04/2008
Date registered
10/04/2008
Date last updated
10/04/2008
Type of registration
Retrospectively registered

Titles & IDs
Public title
Intravenous versus oral iron supplementation for correction of post-transplant anaemia in renal transplant patients.
Scientific title
Intravenous versus oral iron supplementation for correction of post-transplant anaemia in renal transplant patients
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post transplant anaemia in renal transplant recipients. 3011 0
Condition category
Condition code
Renal and Urogenital 3162 3162 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intravenous iron supplementation as single 500mg dose within 5 days of renal transplant surgery.
Intervention code [1] 2751 0
Treatment: Drugs
Comparator / control treatment
Oral iron supplementation, as per current practice of giving 325mg ferrous sulphate, once daily, per oral, until haemoglobin level normalised (>120g/l for males, >110g/l for females).
Control group
Active

Outcomes
Primary outcome [1] 4046 0
Time to normalisation of haemoglobin post renal transplant.
Timepoint [1] 4046 0
3 month follow up post transplant.
Secondary outcome [1] 6808 0
Need for blood transfusions.
Timepoint [1] 6808 0
3 month follow up post transplant.

Eligibility
Key inclusion criteria
1.New live or cadaveric donor renal transplant recipient
2.Aged 18 years or over
3.Able to give written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.Patients with transferrin saturation >50% or ferritin >800µg/l.
2.Women lactating, pregnant or of child-bearing potential not using a reliable contraceptive method.
3.Patients with a history of psychological illness or condition which interferes with their ability to understand or comply with the requirements of the study.
4.Patients who have received a new investigational drug within the last 4 weeks.
5.Intolerance of intravenous or oral iron supplements
6.As the following medications can have interactive effects, they cannot be administered during the course of the study:
-All new investigational medications

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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted 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
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
23/11/2007
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 3269 0
Hospital
Name [1] 3269 0
Princess Alexandra hospital foundation research grant.
Country [1] 3269 0
Australia
Primary sponsor type
Hospital
Name
Princess Alexandra hospital (Department of nephrology)
Address
Department of Nephrology, level 1 ARTS building,
Princess Alexandra hospital, Ipswich road, Woolloongabba, 4102, Qld.
Country
Australia
Secondary sponsor category [1] 2940 0
None
Name [1] 2940 0
Address [1] 2940 0
Country [1] 2940 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5255 0
Princess Alexandra hospital Human Research Ethics committee
Ethics committee address [1] 5255 0
Princess Alexandra hospital, Ipswich road, Woolloongabba, 4102, Qld.
Ethics committee country [1] 5255 0
Australia
Date submitted for ethics approval [1] 5255 0
Approval date [1] 5255 0
04/09/2007
Ethics approval number [1] 5255 0
2007/142
Ethics committee name [2] 5271 0
Princess Alexandra hospital human research ethics committee
Ethics committee address [2] 5271 0
Princess Alexandra hospital, Ipswich road, Woolloongabba, 4102, Qld.
Ethics committee country [2] 5271 0
Australia
Date submitted for ethics approval [2] 5271 0
Approval date [2] 5271 0
04/09/2007
Ethics approval number [2] 5271 0
2007/142

Summary
Brief summary
PROJECT RATIONALE AND OBJECTIVES

Post-transplant anaemia (PTA) remains a common problem after kidney transplantation, with an incidence ranging from nearly 80% at day 0 to about 25% at 1 year. It has been associated with poor graft outcome, and recently has also been shown to be associated with increased mortality.
PTA may occur at any time after renal transplantation. Early PTA (post surgery until 3 months) is most likely to be related to pre-transplant anaemia, the surgery itself, iron deficiency, immunosuppression and infection. Later PTA is more likely to be related to consequences of long-term immunosuppression or a failing graft. All the large scale studies to date have focused mainly on late PTA, and there is a lack of studies looking at the management of early PTA, in particular, the optimal management of iron deficiency.
Our unit routinely administers oral ferrous sulphate to all post transplant patients, however this is not without problems including gastrointestinal intolerance, and interference with the absorption of immunosuppressant medications by leading to significant constipation.
Recently, we have observed that several dialysis patients serendipitously given intravenous iron for treatment of iron deficiency anaemia immediately prior to transplantation, have had better Hb levels in the post-transplant period, without needing oral iron supplementation. In a retrospective case series, Gillespie and Symonds used intravenous ferrous gluconate to treat 15 paediatric and young adult renal transplant recipients and found that doses of up to 250mg induced a statistically significant increase in mean haemoglobin levels. There were only 4 adverse events reported in 3 patients, all self limiting and none life threatening.9 However, there are no trials to date comparing the efficacy of intravenous versus oral iron replacement.
We surmise that giving a single dose of intravenous iron (as ferrous gluconate - Ferrosig®) may be better than a protracted course of oral iron.

Aim
To compare the time to normalisation of Hb post-transplant in patients given a single dose of iv iron as compared with oral iron.

STUDY PROTOCOL AND METHODS
1. Patients
All adult patients receiving a renal transplant at the Princess Alexandra Hospital will be invited to participate in the study. Informed consent will be obtained from all participants.

Inclusion criteria
1.New live or cadaveric donor renal transplant recipient
2.18 years or over
3.Able to give written informed consent.

Exclusions

1.Patients with transferrin saturation >50% or ferritin >800µg/l.
2.Women lactating, pregnant or of child-bearing potential not using a reliable contraceptive method.
3.Patients with a history of psychological illness or condition which interferes with their ability to understand or comply with the requirements of the study.
4.Patients who have received a new investigational drug within the last 4 weeks.
5.Intolerance of intravenous or oral iron supplements
6.As the following medications can have interactive effects, they cannot be administered during the course of the study:
-All new investigational medications

Design:
This is an open-label, randomised, controlled clinical trial in which the primary outcome measure will be the mean time to resolution of PTA (defined as Hb =110 g/l). Patients meeting the inclusion criteria and consenting to participate in the study will be randomly allocated in a 1:1 ratio to either (a) oral iron (ferrous sulphate slow-release 2 tablets mane – the most current practice in the transplant unit) or (b) intravenous iron polymaltose as a 500 mg single dose given within the first 5 days after transplantation.
Randomisation will occur by the use of sequentially numbered, sealed, opaque envelopes with stratification for calcineurin inhibitor type (cyclosporin or tacrolimus). Immunosuppressive therapy will be managed according to our unit’s standard protocols. Patients will have blood tests checked as per our unit’s follow up protocol for recent transplant recipients. We would use these to monitor full blood count, renal function, and calcineurin inhibitor trough levels on a weekly basis, as well as iron studies, B12, and folate at one monthly intervals.

Power and Statistical Analysis
Prospective power calculations have indicated that a minimum of 48 patients in each group would have to be followed up for 3 months in order to have a 90% probability of detecting a halving of the time to correction of haemoglobin levels to =110 g/l in iron-treated patients, assuming an a of 0.05.

Adverse Events During the Investigation
Each patient will be observed closely during the period of the study looking for adverse events. The patient will be removed from the study on clinical grounds in the event of any significant adverse reaction and will then be investigated extensively for the cause. Pre-existing conditions will be excluded from reporting; treatment-emergent signs and symptoms as well as post-treatment adverse events will be recorded on the Adverse Event Case Report Form. Any significant adverse events will be notified to the Ethics Committee of PAH.

Gastrointestinal adverse effects will be defined as the onset of nausea, vomiting, abdominal cramping or diarrhoea. Infusion related reactions will be described as self-limiting flushing sweating, chills, myalgias, arthralgias, bronchospasm and chest pain occurring at the time of the infusion. All infectious episodes and the results of subsequent microbiological investigation will be recorded during the study period.

CLINICAL TRIAL DRUGS

A standard slow-release oral ferrous sulphate (Ferro-gradumet®, Abbott) one tablet daily (equivalent to 105 mg of elemental iron per day) or single intravenous dose of Iron polymaltose (Ferrosig®, Sigma, 500 mg) will be used.

PROCEDURES INVOLVING THE SUBJECT
Patients enrolled in the study will have no extra blood samples collected beyond those normally collected as part of routine transplant follow up.

ASSESSMENT OF PATIENTS
The treating renal physician will be required to give his or her approval prior to patient inclusion in the study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28502 0
Address 28502 0
Country 28502 0
Phone 28502 0
Fax 28502 0
Email 28502 0
Contact person for public queries
Name 11659 0
Associate Professor David Mudge
Address 11659 0
Department of Nephrology,
level 1,
ARTS building,
Princess Alexandra hospital,
Ipswich road,
Woolloongabba, 4102.
Queensland
Country 11659 0
Australia
Phone 11659 0
(07)32405080
Fax 11659 0
Email 11659 0
[email protected]
Contact person for scientific queries
Name 2587 0
Associate Professor David Mudge
Address 2587 0
Department of Nephrology,
level 1,
ARTS building,
Princess Alexandra hospital,
Ipswich road,
Woolloongabba, 4102.
Queensland
Country 2587 0
Australia
Phone 2587 0
(07)32405080
Fax 2587 0
Email 2587 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

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