Does intermittent pneumatic compression reduce the risk of post stroke deep vein thrombosis? The CLOTS 3 trial: study protocol for a randomized controlled trial

BACKGROUND Approximately 80,000 patients each year are admitted to U.K. hospitals with an acute stroke and are immobile. At least 10% will develop a proximal deep vein thrombosis in the first month and 1.5% a pulmonary embolus. Although hydration, antiplatelet treatment and early mobilisation may reduce the risk of deep vein thrombosis, there are currently no preventive strategies which have been clearly shown to be both effective and safe. Anticoagulation increases the risks of bleeding and compression stockings are ineffective. Systematic reviews of small randomized trials of intermittent pneumatic compression have shown that this reduces the risk of deep vein thrombosis in patients undergoing surgery, but that there are few data concerning its use after stroke. The CLOTS trial 3 aims to determine whether, compared with best medical care, best medical care plus intermittent pneumatic compression in immobile stroke patients reduces the risk of proximal deep vein thrombosis. METHODS/DESIGN CLOTS Trial 3 is a parallel group multicentre trial; with centralized randomisation (minimisation) to ensure allocation concealment. Over 80 centres in the U.K. will recruit 2800 immobile stroke patients within the first 3 days of their hospital admission. Patients will be allocated to best medical care or best medical care plus intermittent pneumatic compression. Ultrasonographers will perform a Compression Duplex Ultrasound Scan to detect deep vein thrombosis in each treatment group at about 7-10 days and 25-30 days. The primary outcome cluster includes symptomatic or asymptomatic deep vein thrombosis in the popliteal or femoral veins detected on either scan. Patients are then followed up by postal or telephone questionnaire at 6 months from randomisation to detect later symptomatic deep vein thrombosis and pulmonary emboli and to establish their functional outcome (Oxford handicap scale) and quality of life (EQ5D-3 L). The ultrasonographers performing the scans are blinded to treatment allocation, whereas the patients and caregivers are not. The trial has 90% power to detect a 4% absolute difference in risk of the primary outcome and includes a health economic analysis. DISCUSSION The trial started recruitment in Dec 2008 and will complete recruitment during 2012. It will report results in 2013. TRIAL REGISTRATION NUMBER ISRCTN: ISRCTN93529999.