Boehringer Ingelheim has started what it claims is the biggest ever clinical trial programme in thromboembolic disease, as it moves a new oral thrombin inhibitor, Rendix (dabigatran etexilate), into late-stage development.

The RE-VOLUTION programme will involve more than 27,000 patients worldwide and investigate the use of Rendix to prevent strokes in patients with atrial fibrillation, as well as in the prevention and treatment of deep vein thrombosis after orthopaedic surgery.

Atrial fibrillation is a major unmet need in cardiovascular medicine. It is the most common form of cardiac arrhythmia and accounts for 15% of all strokes, but current treatments have a number of drawbacks. The mainstay of treatment is warfarin, a 50-year-old drug which while orally-available requires time-consuming and costly monitoring and is notorious for interacting with other drugs and food.

The other alternatives are anticoagulants such as the low-molecular weight heparins, but these must be given by injection which makes them unsuitable for long-term use in stroke prevention.

The first Phase III study in RE-VOLUTION, in atrial fibrillation and called RE-LY, has already recruited the first patients of a planned total enrolment of 15,000. It will compare Rendix with warfarin over a period of up to three years.

A number of other companies are vying to develop an effective drug for stroke prevention in atrial fibrillation, but there was a major disappointment last year when one much-anticipated candidate, Sanofi-Aventis and Bristol-Myers Squibb's Plavix (clopidogrel), was found to raise the risk of strokes and heart attacks compared to warfarin in a Phase III trial.

Other products in development for this indication include: AstraZeneca's Exanta (ximelegatran), though this was turned down by the US Food and Drug Administration in 2004, and Bayer's oral Factor Xa inhibitor, BAY 59-7939, currently in Phase II testing.