A trial on unruptured intracranial aneurysms (the TEAM trial): results, lessons from a failure and the necessity for clinical care trials

The trial on endovascular management of unruptured intracranial aneurysms (TEAM), a prospective randomized trial comparing coiling and conservative management, initiated in September 2006, was stopped in June 2009 because of poor recruitment (80 patients). Aspects of the trial design that may have contributed to this failure are reviewed in the hope of identifying better ways to successfully complete this special type of pragmatic trial which seeks to test two strategies that are in routine clinical use. Cultural, conceptual and bureaucratic hurdles and difficulties obstruct all trials. These obstacles are however particularly misplaced when the trial aims to identify what a good medical practice should be. A clean separation between research and practice, with diverging ethical and scientific requirements, has been enforced for decades, but it cannot work when care needs to be provided in the presence of pervasive uncertainty. Hence valid and robust scientific methods need to be legitimately re-integrated into clinical practice when reliable knowledge is in want

Testing devices for the prevention and treatment of stroke and its complications

We are entering a challenging but exciting period when many new interventions may appear for stroke based on the use of devices. Hopefully these will lead to improved outcomes at a cost that can be afforded in most parts of the world. Nevertheless, it is vital that lessons are learnt from failures in the development of pharmacological interventions (and from some early device studies), including inadequate preclinical testing, suboptimal trial design and analysis, and underpowered studies. The device industry is far more disparate than that seen for pharmaceuticals; companies are very variable in size and experience in stroke, and are developing interventions across a wide range of stroke treatment and prevention. It is vital that companies work together where sales and marketing are not involved, including in understanding basic stroke mechanisms, prospective systematic reviews, and education of physicians. Where possible, industry and academics should also work closely together to ensure trials are designed to be relevant to patient care and outcomes. Additionally, regulation of the device industry lags behind that for pharmaceuticals, and it is critical that new interventions are shown to be safe and effective rather than just feasible. Phase IV postmarketing surveillance studies will also be needed to ensure that devices are safe when used in the ‘real-world’ and to pick up uncommon adverse events

Preventing Deep Vein Thrombosis After Stroke: Strategies and Recommendations

The risk of deep vein thrombosis (DVT) after stroke is increased in patients with restricted mobility, a previous history of DVT, dehydration, or comorbidities such as malignant diseases or clotting disorders. Patients with an increased risk of DVT should receive prophylactic treatment. To reduce the chance of DVT, patients should be mobilized as soon as possible and should be kept well hydrated. Anti-embolism stockings cannot be recommended, because they have been demonstrated not useful for preventing DVT or pulmonary embolism in patients with stroke, and they are associated with a significantly increased risk of skin breaks. The usefulness of intermittent pneumatic compression is currently under study in a randomized clinical trial. Treatment with subcutaneously administered low-dose unfractionated heparin is preferred to unfractionated heparin and may be considered in patients with ischemic stroke if the risk of DVT is estimated to be higher than the risk of hemorrhagic complications. Aspirin may also be effective for patients with ischemic stroke who have contraindications to anticoagulants, although direct comparisons with anticoagulants are not available. In patients with intracerebral hemorrhage, low-dose subcutaneous low-molecular-weight heparin is probably safe after documentation of cessation of active bleeding, and may be considered on an individual basis after 3 to 4 days from stroke onset