DIRECTing the fight against blindness

October 31, 2000

The launch of a landmark trial defining a new approach to the treatment of diabetic retinopathy

(London, UK, 1 November 2000) - The launch of the DIabetic REtinopathy Candesartan Trial (DIRECT) programme, takes place today. DIRECT will establish whether treatment with the angiotensin II type 1 (AT1) receptor blocker, candesartan cilexetil, targeting the renin angiotensin system (RAS), can provide effective prevention against the onset and progression of diabetic retinopathy.

Diabetic retinopathy can ultimately lead to blindness in type 1 and type 2 patients with diabetes. In the developed world, diabetic retinopathy is the leading cause of blindness in the working population1 and the most commonly feared complication of diabetes.2 After 20 years of diabetes, nearly all patients with type 1 and over 60 percent of patients with type 2 diabetes will have developed diabetic retinopathy.

DIRECT is the first large-scale, international clinical trial looking at the benefits of RAS blockade in the prevention and treatment of diabetic retinopathy. About 4,500 patients in 20 countries are expected to participate in the DIRECT programme. In this double-blind trial, patients will be assigned to receive up to 32mg of candesartan cilexetil or placebo.

"DIRECT represents an important step forward in the fight against diabetic retinopathy", said Professor Nish Chaturvedi, member of the DIRECT Steering Committee, and Professor of Clinical Epidemiology at Imperial College, London.

"An effective new approach using drug intervention to halt progression, and possibly prevent diabetic retinopathy, would fill a large unmet need in diabetes care. It could dramatically reduce or even avoid the need for laser treatment, limiting retinal damage and preserving an individual's sight."

Previous studies have demonstrated the beneficial effects of glycaemic control and the effective treatment of hypertension. Tight glycaemic control remains the only proven treatment for the prevention of retinopathy placing a heavy burden on both the patient and the health care service.

Retinopathy will still occur in a proportion of diabetic patients treated with tight glycaemic control, therefore there is a need for a supplementary intervention. DIRECT, if successful, will help transform the management of this devastating condition. A new, effective and well-tolerated preventative treatment option would help to relieve the economic burden and suffering that retinopathy causes to millions of diabetic patients.

The DIRECT programme is being conducted and jointly sponsored by AstraZeneca and Takeda Chemical Industries Ltd. EURODIAB, a European diabetes research network, based at University College, London, and Imperial College, London, will be the academic co-ordinating centre.

The DIRECT programme will be overseen by an independent Steering Committee, chaired by Professor Anne-Katrin SjØlie, University of Southern Denmark, Odense. The Steering Committee consists of leading ophthalmologists, diabetologists and epidemiologists, and has scientific responsibility for the DIRECT programme.

Effectively, DIRECT is three separate clinical trials within one programme. Each arm of the programme will investigate the effect of candesartan cilexetil in diabetic, normotensive, normoalbuminuric patients

The three arms will investigate the effects of candesartan cilexetil in:
1. Type 1 diabetic patients without retinopathy for primary prevention.
2. Type 1 diabetic patients with retinopathy for secondary prevention.
3. Type 2 diabetic patients with retinopathy for secondary prevention.

The rationale for DIRECT arose from the promising results of the EURODIAB Controlled Trial of Lisinopril in Insulin dependent Diabetes (EUCLID).4 EUCLID established as its primary endpoint, that the ACE inhibitor, lisinopril, slows the progression of albuminuria in normotensive type 1 diabetic patients.

Importantly, EUCLID also looked at diabetic retinopathy, as a secondary endpoint, and the results suggested that ACE inhibition could delay the progression of diabetic retinopathy. These results highlighted the potential of looking specifically at the benefits of RAS blockade treatment, in a large-scale trial, in diabetic retinopathy. Candesartan cilexetil was chosen for DIRECT because it is a highly effective angiotensin receptor blocker and is generally better tolerated than ACE inhibitors, having placebo-like tolerability.

The prevention and management of diabetic retinopathy is a major challenge in diabetes care. The DIRECT programme has the potential to transform the approach to future care and will provide the answer to a key question - does angiotensin receptor blockade reduce this microvascular complication of diabetes through an effect on the renin angiotensin system?
References 1. Hutchinson A, McIntosh A, Peters J et al. Effectiveness of screening and monitoring tests for diabetic retinopathy - a systematic review. Diabetic Med 2000; 17: 495-506.
2. Dunning PL. Diabetes Education 1995; 21 (N1):58-65.
3. American Diabetes Association. Diabetic Retinopathy. Diabetes Care 2000; 23: S73-76.
4. Chaturvedi N, Sjølie A-K, Stephenson JM and the EUCLID Study Group Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. Lancet 1998; 351: 28-31.

For further information please contact:

Alison MacKenzie
Tel: 0207-465-8737
Fax: 020-7872-9679

Dr. Michael George
Takeda Chemical Industries, Ltd.
Tel: 44-171-484-9000
Fax: 44-171-484-9062

Public Relations Department
Takeda Chemical Industries, Ltd.
Tel: 81-6-6204-2060
Fax: 81-6-6204-2035

Dr Anders Svensson
Tel: 46-32-776-2521
Mob: 46-70-586-2521

Ketchum UK

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