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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.

Condition category

Condition code

Renal and Urogenital

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]

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]

Time to normalisation of haemoglobin post renal transplant.

Timepoint [1]

3 month follow up post transplant.

Secondary outcome [1]

Need for blood transfusions.

Timepoint [1]

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?

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]

Hospital

Name [1]

Princess Alexandra hospital foundation research grant.

Address [1]

Princess Alexandra hospital, Ipswich road, Woolloongabba, 4102, Qld.

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Princess Alexandra hospital Human Research Ethics committee

Ethics committee address [1]

Princess Alexandra hospital, Ipswich road, Woolloongabba, 4102, Qld.

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

04/09/2007

Ethics approval number [1]

2007/142

Ethics committee name [2]

Princess Alexandra hospital human research ethics committee

Ethics committee address [2]

Princess Alexandra hospital, Ipswich road, Woolloongabba, 4102, Qld.

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

Approval date [2]

04/09/2007

Ethics approval number [2]

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

Address

Country

Phone

Fax

Contact person for public queries

Name

Associate Professor David Mudge

Address

Department of Nephrology,
level 1,
ARTS building,
Princess Alexandra hospital,
Ipswich road,
Woolloongabba, 4102.
Queensland

Country

Australia

Phone

(07)32405080

Fax

[email protected]

Contact person for scientific queries

Name

Associate Professor David Mudge

Address

Department of Nephrology,
level 1,
ARTS building,
Princess Alexandra hospital,
Ipswich road,
Woolloongabba, 4102.
Queensland

Country

Australia

Phone

(07)32405080

Fax

[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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No additional documents have been identified.

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