Ischemic Stroke
Conditions
Keywords
DOAC, NOAC (Novel Oral Anticoagulants), Anticoagulation, r-tPA (tissue-type plasminogen activator), Alteplase, Tenecteplase, Rivaroxaban, Apixaban, Dabigatran, Edoxaban
Brief summary
DO-IT is an international, multicenter, prospective, two-arm, randomized, open label, blinded endpoint superiority trial determining the safety and efficacy of intravenous thrombolysis (IVT) in participants experiencing an acute ischemic stroke (AIS) with recent (within the last 48 hours) intake of direct oral anticoagulant (DOAC). For this purpose, 906 adult participants experiencing an AIS with recent DOAC intake will be enrolled at several high-volume international stroke centers and randomly assigned in a ratio of 1:1 to one of two treatment arms: (1) IVT and standard of care/best medical treatment or (2) standard of care/best medical treatment. The DO-IT trial is a definitive test of the hypothesis that IVT is superior to standard of care for achieving better outcome at 90 days in AIS participants with recent DOAC intake.
Interventions
DRUGTenecteplase or Alteplase
Patients randomized to intravenous thrombolysis (IVT) treatment will receive intravenous Tenecteplase or Alteplase.
Sponsors
Insel Gruppe AG, University Hospital Bern
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed consent (deferred consent when possible according to national legislation) * AIS eligible to receive intravenous alteplase/tenecteplase as per standard of care disabling according to the judgement of the treating physician * DOAC ingestion within 48 hours prior to enrollment, or patient with an ongoing prescription of DOAC but exact time point of last intake is unknown. * Either * Can be randomized within 4 hours 15 minutes and treated within 4 hours 30 minutes of last known well time OR * MRI showing a pattern of "DWI-FLAIR-mismatch", i.e. acute ischemic lesion visibly on DWI ("positive DWI") but no marked parenchymal hyperintensity visible on FLAIR ("negative FLAIR") indicative of an acute ischemic lesion ≤4.5 hours of age AND Treatment can be started within 4.5 hours of symptom recognition (e.g., awakening).
Exclusion criteria
* Contra-indications to IVT by the current standard of care of the treating physicians with the exception of recent DOAC intake as specified above. * Intended reversal by specific or unspecific reversal agents * Pregnancy or lactating women. To be reasonable sure to exclude women with ongoing pregnancy, women are not considered of childbearing potential if they fulfill the following criteria * Age \> 55 years OR * Age \< 55 years and at least 12 months since last menstrual period OR * Have had a documented surgical sterilization * Patient \< 18 years of age (since the benefit of IVT is unproven in this population) Since the benefit of IVT might be smaller in patients in which additional endovascular treatment is planned, the investigators will cap patients with intended mechanical thrombectomy at 20% of the trial population. If this number is reached, the following additional exclusion criterion will be applied: * Intended treatment with endovascular reperfusion strategies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modified Rankin Scale (mRS) | 90 days +/- 2 weeks after randomization | Modified Rankin Scale is a scale that runs from 0-6, running from perfect health without symptoms (0) to death (6). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dichotomized modified Rankin Scale (mRS) 0-2 (good functional outcome) | 90 days +/- 2 weeks post-randomization | Modified Rankin Scale is a scale that runs from 0-6, running from perfect health without symptoms (0) to death (6). |
| Change from baseline in stroke severity (National Institutes of Health Stroke Scale, NIHSS) | 24 +/- 12 hours after Intervention | The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. Thus, 0 (minimum score) means "no symptoms", whereas 42 (maximum score) means "severe stroke". |
| Health-related Quality of Life (EuroQol 5D-3L questionnaire) | 90 days +/- 2 weeks post-randomization | The EuroQol 5D-3L (EuroQol 5 Dimensions with each 3 Levels) measures health-related Quality of Life. |
Countries
Austria, Belgium, Canada, Finland, France, Germany, Greece, Netherlands, Norway, Portugal, Spain, Switzerland
Contacts
CONTACTThomas Meinel, MD, PhD
CONTACTFreschta Zipser-Mohammadzada, PhD
STUDY_DIRECTORThomas Meinel, MD, PhD
Insel Gruppe AG, University Hospital Bern
Outcome results
None listed