CREATE Study Answers Key Question on Anaemia Management in Chronic Kidney Disease

Basel, Switzerland, November 16 (ots/PRNewswire) -

- New England Journal of Medicine Article Shows no Additional
Cardiac Benefit From Increasing Haemoglobin to Levels Outside Current
Recommendations

The long awaited results of CREATE (i), a landmark trial that
investigated a key question in nephrology, were published today.
CREATE set out to see if there was additional cardiovascular benefit
in treating anaemia in patients with chronic kidney disease (CKD) to
a haemoglobin level as seen in healthy individuals. The CREATE
results clearly show that there is no additional cardiovascular
benefit from treating to higher haemoglobin levels in this patient
group.[1] CREATE confirms the current anaemia treatment
recommendations of treating to a sub-normal level of haemoglobin and
supports the use of NeoRecormon(R) (epoetin beta) within its current
label. These recommendations are in line with the consensus of the
European Best Practice Guidelines (see Notes to Editors) for all ESAs
(Erythropoiesis Stimulating Agents) like epoetins and darbepoetin
alfa.

Anaemia is an almost universal complication of renal disease. More
patients with chronic kidney disease not yet on dialysis die from
cardiovascular problems than progress to end stage renal disease.[2]
Previous studies have suggested that treating anaemia with epoetin
may improve cardiac outcome. However, the optimal target haemoglobin
range in patients with different stages of chronic kidney disease and
with mild to moderate anaemia has not been determined.

CREATE was the first prospective study completed to date to look
at anaemia treatment and cardiovascular outcomes in patients with
chronic kidney disease not on dialysis. CREATE was designed to answer
the important question of whether complete correction of anaemia
improves cardiovascular outcomes in this patient group compared to
partial anaemia correction and maintenance of haemoglobin at lower
sub-normal levels consistent with current recommendations.

"The vast majority of patients with chronic kidney disease have
anaemia which puts them at high risk of developing cardiovascular
problems. It is therefore reassuring to confirm that we are already
delivering optimal care for patients with mild to moderate anaemia by
treating in line with current clinical experience and guidelines."
commented CREATE principle investigator, Professor Tilman Drüeke of
the Necker Hospital, Paris, France.

About the CREATE study:

The study involved 603 patients with early (stages 3-4) chronic
kidney disease and mild anaemia (haemoglobin 11.0 to 12.5 g/dL).
Patients were randomized to receive NeoRecormon(R) (epoetin beta) at
a starting dose of 2000 IU to correct haemoglobin levels to either
13-15 g/dL (normal 'complete' correction, Group 1) or 10.5-11.5 g/dL
(sub-normal 'partial' correction, Group 2). Subcutaneous
NeoRecormon(R) (epoetin beta) was initiated at randomization (Group
1) or when haemoglobin fell below 10.5 g/dL (Group 2). Patients were
followed up for between 2-4 years.

Key results:

- Early anaemia correction to higher haemoglobin levels did not
alter the time to the primary composite endpoint of eight
cardiovascular events over the study period.

- There were no significant differences in all-cause mortality or
cardiovascular mortality between the study groups. Overall, the
cardiovascular event rate in the study was lower than expected in
both groups.

- Left ventricular mass index (LVMI)(see Notes to Editors)
remained stable, with no significant difference between the two
haemoglobin target groups.

- Patients from Group 1 experienced greater improvements in
quality of life (general health and physical function).

- The time to dialysis was shorter in Group 1 (127 vs. 111 events
for Group 1 and 2 respectively, P=0.034). There was no significant
difference in the change in mean eGFR (estimated Glomerular
Filtration Rate, a measurement of renal function) between both
groups. Initiation of dialysis resulted from the decision from the
treating nephrologist with no protocol-specific criteria.

- Overall, there were no major differences in adverse events
between both groups.

Key conclusion:

The CREATE study results showed that that there is no additional
cardiovascular benefit to be gained by treating pre-dialysis patients
without significant left ventricular hypertrophy (LVH), to reach the
normal haemoglobin range observed in healthy individuals and adds
direct evidence that confirms current best practice guidelines and
supports the use of NeoRecormon(R) within its current label for the
treatment of anaemia.

(i) Cardiovascular risk Reduction with Early Anaemia Treatment by
Epoetin beta

(R) NeoRecormon is a registered trademark of F. Hoffmann-La Roche
and is legally protected. All trademarks used or mentioned in this
release are legally protected. Full prescribing information is
available upon request.

Notes to Editors

1. Patients whose kidneys are failing are unable to secrete
erythropoietin, a protein that is produced by the kidneys and which
stimulates the production of oxygen-bearing red blood cells in the
bone marrow. As a consequence anaemia develops which causes cardiac
ischaemia (lack of oxygen in the heart muscle). The lack of oxygen
means that the heart has to work harder, which in turn leads to left
ventricular hypertrophy (LVH).

2. LVMI is a measurement of LVH, an irreversible condition
featuring an enlarged, diseased heart. LVH can eventually lead to
chronic heart failure (CHF), and other health problems.[3] [4]

3. Current European (EBPG) and USA (NKF-K/DOQI) guidelines
recommend that Hb in CKD patients should be at or greater than 11.0
g/dL. In the US, the guidelines caution when intentionally
maintaining haemoglobin>13 g/dl. There is no specific maximum limit
in the European guidelines.[5] [6]

About Roche

For more information please visit www.roche.com

References

[1] Drüeke et al. Effects of Normalizing Hemoglobin in Chronic
Kidney Disease Patients. NEJM 2006, 355: 2071-84

[2] Dirks JH et al. Kidney Int Suppl. 2005. 68:s1-6.

[3] Collins AJ. Anaemia management prior to dialysis:
cardiovascular and cost-benefit observations. Nephrol Dial
Transplant. 2003. 18(Suppl 2): ii2-ii6

[4] Levin A et al. Prevalent left ventricular hypertrophy in the
predialysis population: identifying opportunities for intervention.
Am J Kidney Dis. 1996. 27:347-354

[5] Revised European Best Practice Guidelines for the Management
of Anaemia in Patients with Chronic Renal Failure. Nephrol Dial
Transplant. 2004; 19: [Suppl 2].

[6] NKF-K/DOQI Clinical practice guidelines and clinical practice
recommendations for anaemia in chronic kidney disease. Am J Kidney
Dis 2006; 47(5 Suppl 3): S11-S15.

ots Originaltext: Roche Pharmaceuticals
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Contact:
For further information please contact Dr Corinne Fründt at Roche,
Tel: +41-61-687-0236, Mobile: +41-79-593-7216. Dr Diane Lorton at
Galliard Healthcare, Tel: +44-207-663-2265, Mobile: +44-7811-358698