SITS-MOST

SITS-MOST
Name	SITS-MOST
Type	multicenter observational study
Start	2002
End	2008
Countries	Netherlands; Germany; France; United Kingdom; Spain; Italy; Sweden; Norway; Denmark; Finland
Interventions	thrombolysis; alteplase; mechanical thrombectomy
Primary outcome	symptomatic intracerebral hemorrhage; mortality
Sample size	6489
Sponsor	European Medicines Agency; Erasmus University Rotterdam; Royal College of Physicians

SITS-MOST

SITS-MOST was a large European postmarketing multicenter registry established to monitor the safety and effectiveness of thrombolytic therapy for acute ischemic stroke after regulatory approval. It was coordinated by academic centers including Erasmus University Rotterdam and regional stroke networks, enrolling patients treated with intravenous alteplase within defined time windows to evaluate hemorrhagic complications, mortality, and functional outcomes compared with prior randomized trials and contemporaneous registries. The study informed practice in numerous NHS settings, academic hospitals such as Karolinska University Hospital, and stroke centers across France, Germany, Spain, and the Netherlands.

Background and Purpose

SITS-MOST was conceived amid regulatory and clinical debates following pivotal trials like NINDS t-PA Stroke Study, ECASS II, and ATLANTIS to provide real-world data on thrombolysis safety across diverse systems including university hospitals such as University College London Hospitals NHS Foundation Trust, tertiary centers like Karolinska Institutet, and regional networks exemplified by Sahlgrenska University Hospital. Sponsors included academic institutions and European regulators such as the European Medicines Agency to address questions raised by cardiology and neurology stakeholders including the European Stroke Organisation and the World Health Organization stroke initiatives. The purpose was to quantify symptomatic intracerebral hemorrhage rates, mortality, and functional recovery using standardized definitions comparable to trials led by teams from Johns Hopkins Hospital and Massachusetts General Hospital.

Study Design and Methods

SITS-MOST used a prospective, observational registry design modeled after trial methodologies from NINDS t-PA Stroke Study and surveillance initiatives like the Get With The Guidelines program. Methods included centralized data collection, predefined imaging review committees with experts from Karolinska Institutet and Erasmus MC, and harmonized definitions for endpoints used in ECASS II and SITS-ISTR. Statistical analyses referenced methods from epidemiology groups at Imperial College London and Harvard School of Public Health. Imaging criteria incorporated assessments familiar to neuroradiology centers such as Guy's and St Thomas' NHS Foundation Trust and neurovascular surgeons from Charité – Universitätsmedizin Berlin.

Patient Population and Inclusion Criteria

The registry enrolled adults presenting with acute ischemic stroke who received intravenous alteplase within time windows aligned to guidance from panels including the American Heart Association and the European Stroke Organisation. Participating centers ranged from academic tertiary referral hospitals like Addenbrooke's Hospital to community stroke units in regions served by Helsinki University Hospital. Inclusion criteria mirrored those in landmark trials such as ECASS III, excluding patients with hemorrhagic stroke on baseline CT scans interpreted by neuroradiologists affiliated with institutions like UCLA Health and Mount Sinai Hospital. Demographic and comorbidity data included factors commonly recorded in cohorts studied by investigators from Mayo Clinic and Cleveland Clinic.

Outcomes and Endpoints

Primary safety endpoints were rates of symptomatic intracerebral hemorrhage using definitions comparable to ECASS II and 90-day mortality benchmarks reported in NINDS t-PA Stroke Study. Functional outcomes were measured by the Modified Rankin Scale assessed at 90 days, a metric used in trials coordinated by Massachusetts General Hospital and Oxford University Hospitals NHS Foundation Trust. Secondary endpoints included early neurological improvement assessed with the National Institutes of Health Stroke Scale as used in protocols at Johns Hopkins Hospital and Stanford Health Care.

Key Findings and Results

SITS-MOST reported symptomatic intracerebral hemorrhage rates and 90-day mortality broadly consistent with randomized evidence from NINDS t-PA Stroke Study and ECASS II, while documenting real-world variations across centers like Karolinska University Hospital, Charité – Universitätsmedizin Berlin, and Erasmus MC. The registry highlighted associations between outcome and treatment delay, echoing findings from ECASS III and observational analyses by teams at Harvard Medical School. Subgroup analyses paralleled work from Mayo Clinic and Cleveland Clinic showing worse outcomes in older patients and those with higher baseline National Institutes of Health Stroke Scale scores, similar to patterns reported by the Australian Stroke Clinical Registry.

Safety and Adverse Events

Safety monitoring emphasized symptomatic intracerebral hemorrhage, systemic bleeding, and mortality, with adjudication by expert panels from institutions such as Karolinska Institutet and Imperial College London. Adverse event rates were benchmarked against prior trials including NINDS t-PA Stroke Study and postmarketing surveillance like registries coordinated by American Heart Association. The registry contributed data that informed risk stratification algorithms used in practice at centers like Addenbrooke's Hospital and UCLH.

Impact on Clinical Practice and Legacy

Findings from SITS-MOST influenced guideline updates by bodies including the European Stroke Organisation and the American Heart Association, reinforced implementation of thrombolysis pathways in stroke centers such as Royal Melbourne Hospital and Karolinska University Hospital, and catalyzed quality-improvement registries like Get With The Guidelines. The registry's methodology informed subsequent trials and registries including the SITS-ISTR database and contributed to evolving practices combining alteplase with mechanical thrombectomy techniques refined at centers like Massachusetts General Hospital and Charité – Universitätsmedizin Berlin. SITS-MOST remains cited in guideline documents from organizations such as the World Stroke Organization and has a legacy in harmonizing postmarketing surveillance across European stroke networks.

Category:Clinical trials