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Efficacy and safety of thrombectomy in stroke with extended lesion and extended time window: a randomized, controlled trial

Periodic Reporting for period 2 - TENSION (Efficacy and safety of thrombectomy in stroke with extended lesion and extended time window: a randomized, controlled trial)

Reporting period: 2019-07-01 to 2020-12-31

TENSION (efficacy and safety of ThrombEctomy iN Stroke with extended leSION and extended time window: a randomized, controlled trial) strives at providing innovative treatment to patients with severe stroke to reduce the individual and societal burden of death and dependency from stroke. To this end, TENSION is a randomized, controlled, prospective, open label, blinded endpoint (PROBE) trial of thrombectomy in stroke patients with extended ischemic stroke lesions and patients presenting in a late time window, who are excluded from available effective treatment approaches based on current knowledge and guidelines. The aim of TENSION is to provide evidence to guide effective treatment in these patients. The trial will enroll up to 665 subjects in eight European countries. Outcome evaluation will involve a comprehensive array of clinical and safety parameters, health and socio-economic outcomes including patient reported outcome measures (PROM) for evaluation according to the principles of value-based healthcare. Health economic evaluation with cost-effectiveness analysis will be performed and gender-effects on treatment and outcome will be studied.
Stroke is a major cause of death and disability in Europe with a large social and economic impact on patients, families, and society. The burden of stroke is in large parts determined by severe strokes resulting from the occlusion of large brain-supplying arteries. About 1.5 million people suffer from stroke in the EU each year with 10-20% severe strokes that might be candidates for thrombectomy, but in whom the benefit of treatment is uncertain. Based on current knowledge, no effective treatment is available for these patients, if brain lesions resulting from stroke are already extended and if patients arrive late in hospital, i.e. up to 12 hours of symptom onset. The central objective of TENSION is to assess whether stroke treatment using an existing currently available intervention, i.e. thrombectomy, improves clinical outcome, survival and quality of life in severe stroke patients with extended lesions and in an extended time window, as well. By this, TENSION will increase the population of stroke patients that may effectively be treated with thrombectomy. The larger demand for stroke thrombectomy together with the unequivocal demonstration of clinical benefit in a randomized controlled trial will foster area-wide implementation of thrombectomy and support establishment of interventional stroke in all European countries.
During the first reporting period the main task was the set-up of the framework trial and the start of the clinical trial. The trial protocol was finalized, required approvals were received, all necessary trial boards and committees were constituted. Standards for image assessment and thrombectomy within the clinical trial have been defined and made available to all investigators. A workflow for central image reading was established and an image database set up. The clinical trial protocol was reviewed, sample size calculation was completed, a plan for statistical analysis was drafted.
During the second reporting period the main tasks were related to the clinical trial and enrolment of patients in the clinical trial. We had to face challenges imposed by the COVID-19 pandemic with its impact on stroke patient treatment across all countries but accompanied by effective measures and communication with the investigators the trial kept enrolling continuously. As patient enrolment was found to fall behind the expected enrolment rates, a pre-planned contingency plan was deployed. The trial was extended to two new countries (Canada and Spain), and new trial sites were identified and opened. By the end of the second reporting period, 30 trial sites are active in 8 countries, and 117 patients have been enrolled in TENSION.
All trial-related boards are working effectively. The image core lab is continuously evaluating all images acquired within the trial. The DSMB has evaluated the first safety report and did not have any safety concerns but encouraged continuation of the trial. The process of online image analysis training and certification of trial investigators is running effectively. 144 readers have been qualified since start of the project. In an accompanying scientific analysis, interrater variability was analyzed for the first 100 qualified readers and published. Interrater agreement reliability for total ASPECTS and study enrollment appeared sufficient for practical application.
A health-economic analysis plan was developed. Dissemination, communication and exploitation activities were continued, including regular meetings of the Innovation and Exploitation Management Board.
The overall ambition of TENSION is to make effective treatment available for severe stroke patients and by this to improve functional outcome and quality of life of thousands of stroke patients in Europe and to reduce the individual, societal and economic burden of death and disability resulting from severe stroke. It is especially the severe strokes that are responsible for the huge immediate and secondary individual and societal strain caused by death, dependency, persistent disability and follow-up costs.
TENSION will provide effective treatment to a large new group of patients. The large group of severe stroke patients that is studied in TENSION has been neglected by previous thrombectomy trials. There is no convincing evidence for the benefit of thrombectomy and current guidelines do not provide specific treatment for these patients. Moreover, information on the effect of thrombectomy for acute stroke is largely limited to a single device, while I clinical practice numerous devices are used. Finally, there is only limited information on quality of life after stroke thrombectomy. TENSION progresses beyond the state of the art by addressing these open questions by providing evidence for the benefit of thrombectomy in this new group of patients, providing data on the use of different devices for thrombectomy, and providing information on quality of life after thrombectomy for severe stroke. The results of our trial will end uncertainty allow future treatment decisions based on evidence.
TENSION addresses an important health problem in the EU and has the potential to provide a manifest benefit for individual patients, doctors involved in the management of stroke, and the society at large. The annual costs of stroke in Europe are estimated at more than € 64 billion, of which about two thirds are direct healthcare costs, and 4 million DALYs are lost each year due to stroke in the EU. We expect the following impacts: At the individual patients’ level, TENSION will provide evidence for more effective and safe treatment of severe stroke; TENSION will improve functional outcome and avert death and disability in individual stroke patient; At the societal level, TENSION will reduce the burden of death and disability from severe stroke. TENSION will increase the target population for effective thrombectomy; TENSION will reduce the costs of stroke care by reduction of disability and dependency; TENSION will support health equity across Europe by providing evidence of the benefit of thrombectomy in different European countries with diverse healthcare systems.