Intravenous Thrombolysis for Ischemic Stroke

(DO-IT Trial)

Recruiting at 14 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether intravenous thrombolysis (IVT) is more effective than usual care for individuals who have experienced an ischemic stroke (caused by a blocked blood vessel) and have recently taken blood thinners known as DOACs. Participants will receive either IVT with medications like Alteplase or Tenecteplase, both clot-busting drugs, along with standard care, or standard care alone. The trial aims to determine which approach results in better recovery after 90 days. Individuals may qualify if they have had a recent ischemic stroke and took a DOAC within the last two days. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment benefits more patients.

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 is the safety track record for Alteplase and Tenecteplase?

Research shows that both Alteplase and Tenecteplase, the treatments studied in this trial, have been used to treat sudden strokes caused by blocked blood flow to the brain.

Studies have found that Alteplase is generally safe for stroke patients. It has been widely used, with substantial evidence supporting its safety. However, like any treatment, it carries risks, and some patients may experience side effects such as bleeding.

Tenecteplase is also used for this type of stroke and is considered a safe alternative to Alteplase. Research suggests it may aid recovery, though there remains a chance of side effects like bleeding in the brain.

Both treatments have undergone testing in people, and their safety is well-documented. They are generally well-tolerated, but as with any medical treatment, potential risks and side effects exist. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for ischemic stroke because they offer potentially faster and more effective options for breaking down blood clots. Unlike the standard of care, which typically uses Alteplase, Tenecteplase might work more quickly due to its longer half-life and faster clot-busting action. This could mean better outcomes for patients, as it allows for a more extended treatment window and potentially fewer side effects. Additionally, both drugs are administered intravenously, ensuring rapid delivery to the site of the clot, which is crucial during a stroke.

What evidence suggests that this trial's treatments could be effective for acute ischemic stroke?

In this trial, participants will receive either Alteplase or Tenecteplase as part of the intravenous thrombolysis treatment arm. Research has shown that both drugs effectively treat sudden strokes caused by blocked blood flow, known as acute ischemic stroke (AIS). Alteplase has been linked to better long-term survival and improved recovery, with studies finding significant improvements in patients' conditions. Tenecteplase, meanwhile, also leads to excellent recovery and aids early improvement in brain function. Studies suggest that Tenecteplase serves as a good alternative to Alteplase, offering similar benefits for treating AIS. Both treatments have demonstrated promising results in helping patients recover more effectively from strokes. ^{3 5 6 7 8}

Who Is on the Research Team?

Thomas Meinel, MD, PhD

Principal Investigator

Insel Gruppe AG, University Hospital Bern

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12482200/

Low-dose vs. standard-dose alteplase for acute ischemic ... This study aims to comprehensively compare the effectiveness and safety of low-dose versus standard-dose alteplase in a sample of Iranian ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2831320

Safety and Effectiveness for Tenecteplase and Alteplase in ... This comparative effectiveness study compares the clinical effectiveness and safety of tenecteplase and alteplase for the treatment of acute ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2400314

Reteplase versus Alteplase for Acute Ischemic Stroke Among patients with ischemic stroke within 4.5 hours after symptom onset, reteplase was more likely to result in an excellent functional outcome than alteplase.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1052305725000096

Comparative efficacy and safety of tissue plasminogen ... Reteplase 18+18 mg and TNK 0.25 mg/kg demonstrated higher efficacy and comparable safety to ALT. Larger trials are needed to further explore these agents as ...

5. ahajournals.org ahajournals.org/doi/10.1161/strokeaha.114.006570

Acute Ischemic Stroke and Long-Term Outcome After ... Treatment with intravenous tPA in patients with ischemic stroke was associated with improved long-term survival.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2686258/

Safety and efficacy of alteplase in the treatment of acute ... The aim of this review is to report data on safety and efficacy of rt-PA in treatment of ischemic stroke. Structure and mechanisms of action. Tissue plasminogen ...

7. activase.com activase.com/ais/stroke-reporting/analyze-process-and-outcomes.html

Analyze Process and Outcomes | Activase® (alteplase) Examine discharge data. Review files of patients with a discharge diagnosis of acute ischemic stroke (AIS). Identify missed eligible patients

8. ahajournals.org ahajournals.org/doi/10.1161/CIRCOUTCOMES.119.006031

Safety and Outcomes of Intravenous tPA in Acute Ischemic ... Collected data include patient demographics and medical history, including stroke, medications before admission, in-hospital treatment, and in- ...