Clinical trial NCT00202345: Iron Sucrose in Stage 3/4 Kidney Disease
Official title: Assessment of the Use of Intravenous Iron Sucrose to Maintain Haemoglobin Levels and Delay the Onset of Use of Erythropoietic Agents and/or Dialysis in Stage 3/4 Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Kidney Failure
Anemia
Keywords: Creatinine Clearance
Hemoglobin
Iron sucrose
Oral iron therapy
Ferritin
Transferrin saturation
Iron
Lead sponsor: Melbourne Health
Sponsor class: OTHER
First posted: 2005-09-20
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: One of the complications of late stage kidney disease is the development of a low red blood cell count (anaemia/low haemoglobin concentration). The Australian Commonwealth government limits funding of medications (called erythropoietic stimulating agents) to those patients who have already developed anaemia.

There is evidence supporting the beneficial effects of maintaining a higher haemoglobin in these patients. Higher haemoglobin can delay the onset of dialysis and reduce the development of heart enlargement. However, the administration of erythropoietic stimulating agents is not without risk, including a high financial burden, worsening of high blood pressure and a rare complication called pure red cell aplasia.

Previous studies have shown that patients with chronic kidney disease require additional iron to maintain the production of red blood cells. Thus it would be timely to determine if the administration of iron sucrose to these patients can maintain a near normal haemoglobin concentration, without the need to start an erythropoietic stimulating agent and possibly delaying dialysis.

Study Hypothesis: That administration of iron sucrose is superior to standard care in the prevention of anaemia in patients with stage 3 /4 kidney disease.

Detailed description: Eligible patients will be approached. Those who agree to partake in the study will, after enrolment (including informed consent), be randomized to one of 2 groups.

Group A: To receive intravenous iron sucrose to maintain supra-physiological measures of iron status ) Group A will be targeted to have ferritin levels between 300 and 500µg/L and/or a transferrin saturation of between 25 and 50%. Between 100 and 200mg of intravenous iron sucrose will be administered by slow bolus injection one- to two-monthly to achieve these levels.

Oral iron will not be used routinely in this group.

Group B: Will have oral iron therapy if required to maintain ferritin levels between 100 and 150µg/L and/or transferrin saturations \>20% but \<25%. Patients in Group B who are unable to tolerate oral iron will be administered iron sucrose if necessary to maintain acceptable iron levels.

Patients in Group B will therefore differ from those in Group A (a) through the routine use of iron sucrose and (b) through the maintenance of different ferritin and transferrin saturation levels.

Eligibility criteria: Inclusion Criteria:

1. Initial Hb concentrations ≥ 110g/L (males and females)
2. Calculated GFR ≤ 35mL/min (≤ 50mL/min for diabetics)
3. Demonstration of a clinically significant rise in creatinine and/or a drop in Hb concentration in the previous 18 months. If such data are not available, the investigator will make a decision regarding eligibility based on the clinical circumstances.

Exclusion Criteria:

1. Age \> 80
2. Pregnancy\*
3. Unstable ischaemic heart disease\*
4. Uncontrolled, severe, congestive cardiac failure
5. Haemochromatosis or iron overload\* (ferritin \>300µg/L and TSAT \>25%)
6. Liver failure
7. Myelodysplastic syndromes or monoclonal gammopathies
8. Active malignancy or gastrointestinal bleeding\*
9. Persistent sepsis\* or significant chronic inflammation (CRP \> 25)\*
10. Iron deficiency\* (Ferritin \<30ug/L and Tsat \<15%)or other haematinic disorder
11. Active and significant haemolysis\*
12. Previous organ transplantation
13. Concurrent or significant past (\>6 months) immuno-suppression
14. Adult polycystic kidney disease
15. Current use of an ESA
16. On dialysis \*: patients can still be considered eligible after condition is reversed or treated

Primary outcomes:
measure: The primary endpoint will be the change in Hb concentration at 12 months or termination (dialysis, commencement of an ESA). Minimum permitted enrolment is 6 months.
Secondary outcomes:
measure: The secondary endpoints will be the change in renal function (calculated creatinine clearance), the quality of life, the time taken to dialysis, the time from randomization to the requirement of an ESA and the number of hospitalization days.
Other outcomes:
Locations:
city: Gosford
country: Australia
facility: Central Coast Health
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hospital
state: Queensland
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Melbourne
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
Study officials:
affiliation: Melbourne Health
name: Lawrence P McMahon, MD
role: PRINCIPAL_INVESTIGATOR
References: