Intravenous Thrombolysis for Ischemic Stroke

(DO-IT Trial)

Recruiting at 13 trial locations

Overseen By Thomas Meinel, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Insel Gruppe AG, University Hospital Bern

Must be taking: DOACs

Must not be taking: Reversal agents

Disqualifiers: Pregnancy, Under 18, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Immediate intervention upon randomization

906 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it involves participants who have recently taken direct oral anticoagulants (DOACs). It seems you can continue taking DOACs, as the trial includes people who have taken them within the last 48 hours.

What data supports the effectiveness of the drug for ischemic stroke?

Research shows that tenecteplase is as effective as alteplase, the only approved drug for treating acute ischemic stroke, in helping patients recover when given within 4.5 hours of symptom onset. ^{1 2 3 4 5}

Is intravenous thrombolysis for ischemic stroke safe?

Research shows that tenecteplase and alteplase, both used for treating strokes, have similar safety profiles, meaning they are generally safe for humans. Studies found no significant differences in serious side effects like brain bleeding or death between the two treatments. ^{1 6 7 8 9}

How does the drug for ischemic stroke differ from other treatments?

Alteplase is the only approved drug for acute ischemic stroke, working by dissolving blood clots to restore blood flow to the brain. Tenecteplase, a newer alternative, is genetically engineered to have a longer half-life and greater specificity for clots, potentially offering more effective and faster recovery, although it is not yet approved for this use. ^{1 3 5 10 11}

Research Team

Thomas Meinel, MD, PhD

Principal Investigator

Insel Gruppe AG, University Hospital Bern

Eligibility Criteria

This trial is for adults who've had a stroke within the last 48 hours and have taken direct oral anticoagulants (DOACs) recently. It's not suitable for those with certain medical conditions or treatments that could interfere with the study.

Inclusion Criteria

Informed consent (deferred consent when possible according to national legislation)

I am eligible for a clot-dissolving drug as decided by my doctor.

I have taken a blood thinner within the last 48 hours or am prescribed one but unsure when I last took it.

Exclusion Criteria

My doctor advises against IVT for me, except for recent DOAC use.

I am planned to receive a treatment to reverse my condition.

I am not part of the 20% receiving mechanical thrombectomy in the trial.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either intravenous thrombolysis with Tenecteplase or Alteplase and standard of care, or standard of care alone

Immediate intervention upon randomization

1 visit (in-person)

Initial Follow-up

Participants are monitored for symptomatic intracranial hemorrhage and changes in stroke severity

36 hours

Continuous monitoring

Extended Follow-up

Participants are assessed for health-related quality of life and functional outcomes using the Modified Rankin Scale

90 days

Periodic assessments

Treatment Details

Interventions

• Alteplase
• Tenecteplase

Trial Overview The DO-IT trial is testing whether intravenous thrombolysis (IVT), using drugs Tenecteplase or Alteplase, can improve outcomes in stroke patients on DOACs better than standard care alone. Participants are randomly chosen to receive either IVT plus standard care or just standard care.

Participant Groups

Group I: Intravenous Thrombolysis + Best medical treatment (standard of care) Experimental Treatment 1 Intervention

Patients will receive intravenous administration of Tenecteplase or Alteplase.

Group II: Best Medical Treatment (standard of care) Active Control 1 Intervention

Patients will receive Standard of care/Best medical treatment according to local applicable guidelines, including the current American Heart Association/American Stroke Association (AHA/ASA) and European Stroke Organisation/ European Society of Minimally Invasive Neurological Therapy (ESO/ESMINT) guidelines.

Alteplase is already approved in United States, European Union for the following indications:

Approved in United States as Activase for:

• Acute ischemic stroke
• Acute myocardial infarction
• Pulmonary embolism
• Blocked central venous catheter

Approved in European Union as Actilyse for:

• Acute ischemic stroke
• Acute myocardial infarction
• Pulmonary embolism
• Blocked central venous catheter

Who Is Running the Clinical Trial?

Insel Gruppe AG, University Hospital Bern

Lead Sponsor

Trials

831

Recruited

2,353,000+

Findings from Research

In a study involving 1585 patients across 5 randomized clinical trials, tenecteplase showed significantly greater complete recanalization and early neurological improvement compared to alteplase in treating acute ischemic stroke.

Both treatments had similar safety profiles, with no significant differences in rates of recovery, functional independence, or serious complications like intracerebral hemorrhage, indicating that tenecteplase is at least as effective and safe as alteplase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenecteplase versus alteplase for management of acute ischemic stroke: a pairwise and network meta-analysis of randomized clinical trials. Kheiri, B., Osman, M., Abdalla, A., et al.[2018]

A comprehensive analysis of 19,514,140 case reports revealed that while tenecteplase is as effective as alteplase for treating acute ischemic stroke, it has a higher incidence of serious adverse events (AEs) such as death and cardiogenic shock, indicating potential safety concerns.

Unexpected adverse reactions, including ocular issues and pneumonia aspiration, were identified with tenecteplase, highlighting the need for ongoing monitoring to ensure patient safety before it can be considered a full alternative to alteplase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing adverse events of tenecteplase and alteplase: a real-world analysis of the FDA adverse event reporting system (FAERS). Shi, FE., Yu, Z., Sun, C., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Tenecteplase versus alteplase for stroke thrombolysis evaluation (TASTE): A multicentre, prospective, randomized, open-label, blinded-endpoint, controlled phase III non-inferiority trial protocol. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Effect of Time to Thrombolysis on Clinical Outcomes in Patients With Acute Ischemic Stroke Treated With Tenecteplase Compared to Alteplase: Analysis From the AcT Randomized Controlled Trial. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

In acute ischemic stroke, early IV tenecteplase was noninferior to alteplase for excellent functional outcome. [2022]

5. France pubmed.ncbi.nlm.nih.gov

Tenecteplase in acute ischemic stroke: Review of the literature and expert consensus from the French Neurovascular Society. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Tenecteplase versus alteplase for management of acute ischemic stroke: a pairwise and network meta-analysis of randomized clinical trials. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Intravenous Thrombolytics in the Treatment of Acute Ischemic Stroke. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Making a case for the right '-ase' in acute ischemic stroke: alteplase, tenecteplase, and reteplase. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Comparing adverse events of tenecteplase and alteplase: a real-world analysis of the FDA adverse event reporting system (FAERS). [2023]

10. Croatia pubmed.ncbi.nlm.nih.gov

Thrombolysis for acute ischemic stroke--our experiences as part of SITS-MOST. [2010]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Intravenous Tenecteplase Bolus in Acute Ischemic Stroke: Results of Two Open-Label, Multicenter Trials. [2018]