Safety and Efficacy of Intravenous Thrombolysis in Patients with Ischemic Stroke on Treatment with Direct Oral Anticoagulants: DO-IT – The DOAC Intravenous Thrombolysis trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Insel Gruppe AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

4 Aug 2025 → ongoing

Decision date (initial)

2026-01-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-515561-34-01

ClinicalTrials.gov

NCT06571149

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

The DO-IT trial is a definitive test of the hypothesis that the strategy of IVT (with either alteplase or tenecteplase) is
superior to standard of care for achieving better outcome (functional outcome quantified by a shift on
the modified Rankin Scale, mRS) at 90 days in AIS patients with recent DOAC ingestion who are
otherwise eligible for IVT according to local standards of care.

Conditions and MedDRA coding

Acute ischemic stroke with recent ingestion of direct oral anticoagulants.

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Informed consent (deferred consent when possible according to national legislation)
2. AIS eligible to receive intravenous alteplase/tenecteplase as per standard of care disabling according to the judgement of the treating physician
3. 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.
4. Either o Can be randomized within 4 hours 15 minutes and treated within 4 hours 30 minutes of last known well time OR o 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 5

1. Contra-indications to IVT by the current standard of care of the treating physicians with the exception of recent DOAC intake as specified above.
2. Intended reversal by specific or unspecific reversal agents
3. 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 o Age > 55 years OR o Age < 55 years and at least 12 months since last menstrual period OR o Have had a documented surgical sterilization
4. Patient < 18 years of age (since the benefit of IVT is unproven in this population)
5. Since the benefit of IVT might be smaller in patients in which additional endovascular treatment is planned, we 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. modified Rankin Scale (mRS, functional outcome) at 90 days ± 2 weeks (shift analysis)

Secondary endpoints 6

1. Dichotomized good functional outcome (mRS 0-2 or return to baseline at day 90 (±2 weeks))
2. change in stroke severity (National Institutes of Health Stroke Scale and ischemic stroke volume) between baseline and 24 ± 12 hours
3. health-related Quality of Life (EuroQol 5D-3L) at 90 days ± 2 weeks
4. symptomatic intracranial hemorrhage within the first 36 hours (European Co-operative Acute Stroke Study-II definition)
5. major extracranial bleeding up to 24 ± 12 hours
6. all-cause mortality up to 7 days after admission or until discharge

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Insel Gruppe AG

Sponsor organisation

Insel Gruppe AG

Address

Freiburgstrasse 18

City

Bern

Postcode

3010

Country

Switzerland

Scientific contact point

Organisation

Insel Gruppe AG

Contact name

Thomas Meinel

Public contact point

Organisation

Insel Gruppe AG

Contact name

Thomas Meinel

Sponsor responsibilities

Article 77 compliance

Insel Gruppe AG

Contact point sponsor

Insel Gruppe AG

Article 77 implementation

Insel Gruppe AG

Locations

9 EU/EEA countries · 80 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 94 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications