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

Periodic Reporting for period 3 - TENSION (Efficacy and safety of thrombectomy in stroke with extended lesion and extended time window: a randomized, controlled trial)

Période du rapport: 2021-01-01 au 2022-06-30

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. 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 third reporting period the main tasks were related to the clinical trial and enrolment of patients in the clinical trial. Challenges to the trial imposed by the COVID-19 pandemic continued with effects on patient enrolment and activation of new sites in all countries. However, accompanied by mitigation measures and intensified communication with the investigators the trial kept enrolling continuously. We continued measures from the contingency plan, which was deployed in the second funding period, including the activation of new sites in already participating countries, and the extension of the trial to further countries (currently being prepared for Hungary, Ireland, Italy, and Switzerland). By the end of the third reporting period, 33 trial sites are active in 9 countries, and 209 patients have been enrolled in TENSION.
The results RESCUE-Japan-LIMIT trial, which demonstrated a benefit of thrombectomy as compared to standard care in patients with large vessel occlusion and MRI-defined ASPECTS of 3-5 within 6 hours of symptom onset, were published, and the Steering Committee decided to continue enrollment in TENSION, as the results of this trial cannot be transferred to the target population of TENSION.
All trial-related boards and committees are working effectively. The image core lab is continuously evaluating all images acquired within the trial, and the quality of image judgement by local investigators is good. A scientific analysis of interobserver agreement of the first 100 TENSION investigators completing the image training was published providing further insights into the expected variance in image judgement results. The DSMB has evaluated the 2nd and 3rd annual safety report and did not have any safety concerns but encouraged continuation of the trial. The Statistical Analysis Plan for the trial was finalized based on the final study protocol. For health-economic analysis, a Markov model structure is being developed to evaluate the long-term economic consequences of endovascular thrombectomy compared with best medical care, and to estimate the influence on health-related quality of life. Dissemination, communication and exploitation activities were continued, including regular meetings of the Innovation and Exploitation Management Board and round-table meetings with members of the industry and scientific societies. Initiated by the TENSION consortium, together with the coordinating investigators of the other ongoing and completed trials of thrombectomy in patients with low ASPECTS a pooled analysis of the individual trials is planned, and an analysis plan was drafted.

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 in 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.

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Periodic Reporting for period 3 - TENSION (Efficacy and safety of thrombectomy in stroke with extended lesion and extended time window: a randomized, controlled trial)

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