Multiple Treatments for Stroke

(ACT-GLOBAL Trial)

Recruiting at 1 trial location

Overseen By Bijoy Menon, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: The George Institute

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

20000 Participants Needed

Trial Summary

What is the purpose of this trial?

Stroke is causing 6.6 million deaths and is a major cause of disability worldwide in 2019. There remains an urgent need for interventions that improve outcomes which can be implemented with wide applicability for stroke. ACT-GLOBAL is a multi-factorial, multi-arm, multi-stage, randomised, global adaptive platform trial for stroke, aiming to identify the treatment/s associated with the highest chance of improving outcome in stroke patients. In ACT-GLOBAL multiple questions will be evaluated simultaneously and sequentially as data accrues and can evaluate interactions between different treatment options.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It may depend on the specific treatment domain you are enrolled in, so it's best to discuss this with the trial coordinators.

What data supports the effectiveness of the ACT-GLOBAL Adaptive Platform Trial treatment for stroke?

The research highlights the potential of adaptive trial designs and precision medicine to improve stroke treatment outcomes. Although no specific neuroprotectant has been identified, these approaches may enhance the effectiveness of treatments by tailoring them to individual patient characteristics and optimizing trial methodologies. ^{1 2 3 4 5}

What safety data exists for treatments in stroke clinical trials?

Research shows that adverse events (unwanted side effects) are common in stroke trials, but most are not related to the treatment being tested. A systematic review of drugs for stroke recovery also looked at safety, indicating ongoing evaluation of treatment safety in these trials. ^{6 7 8 9 10}

How does the ACT-GLOBAL Adaptive Platform Trial treatment for stroke differ from other treatments?

The ACT-GLOBAL Adaptive Platform Trial is unique because it uses precision medicine, which means it tailors treatment based on individual characteristics like genetics and biomarkers (measurable indicators in the body), to optimize stroke recovery. This approach is different from traditional treatments that apply the same method to all patients, regardless of their unique biological makeup. ^{3 5 11 12 13}

Research Team

Craig Anderson, MD, PhD

Principal Investigator

The George Institute

Michael D Hill, MD

Principal Investigator

University of Calgary

Xiaoying Chen, PhD

Principal Investigator

The George Institute

Bijoy Menon, MD

Principal Investigator

University of Calgary

Andrew Demchuk, MD

Principal Investigator

University of Calgary

Eligibility Criteria

This trial is for adults over 18 years old who have been clinically diagnosed with a stroke. It's designed to find treatments that can be widely used to improve outcomes after a stroke.

Inclusion Criteria

I have been diagnosed with a stroke.

Platform

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various interventions for stroke, including blood pressure management, thrombolysis, and other experimental treatments

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days in Ischaemic Stroke State; 6 months in Intracerebral Haemorrhage State

Adaptive Analysis

Frequent adaptive analyses are conducted to assess the efficacy of interventions and adjust the trial design accordingly

Treatment Details

Interventions

• ACT-GLOBAL Adaptive Platform Trial

Trial Overview ACT-GLOBAL is testing various interventions like deferoxamine mesylate, colchicine, different blood pressure control strategies, and tenecteplase in multiple combinations against placebo to see which improves stroke outcomes the most.

Participant Groups

Group I: IV thrombolysis domain Experimental Treatment 3 Interventions

This domain has a prospective, randomized, controlled, open-label, parallel group with blinded endpoint assessment (PROBE) design to optimize the use of intravenous Tenecteplase in participants with Acute Ischemic Stroke.

Group II: INTERACT5 Domain Experimental Treatment 4 Interventions

This is a domain within the Intracerebral Haemorrhage State of the ACT-GLOBAL adaptive platform trial for stroke. The objective of this domain is to determine the efficacy of intravenous deferoxamine and low-dose oral colchicine, both individually and in combination, compared to standard of care alone, on improving functional outcome in patients with acute spontaneous supratentorial ICH.

Group III: Blood Pressure domain Experimental Treatment 3 Interventions

Third Enhanced Control of Hypertension and Thrombectomy Stroke Study (ENCHANTED3/MT) as a domain of ACT-GLOBAL to compare three BP lowering management strategies, that of conservative, moderate and intensive BP lowering in patients with Acute Ischaemic Stroke admitted to participating hospitals who has an elevated SBP after reperfusion therapy via Endovascular Thrombectomy, and reliably determine, which approach leads to improved functional outcome. Locally available and approved i.v. BP lowering agents can be used in this domain.

Group IV: ACT-42 domain Experimental Treatment 2 Interventions

This domain has a Phase 2b, multicenter, prospective, randomized, open label, blinded-endpoint (PROBE) controlled single-dose adaptive design and aim to determine the efficacy and safety of NoNO-42 in participants with Acute Ischaemic Stroke selected for thrombolysis with or without Endovascular Thrombectomy.

Who Is Running the Clinical Trial?

The George Institute

Lead Sponsor

Trials

84

Recruited

275,000+

University of Calgary

Collaborator

Trials

827

Recruited

902,000+

Berry Consultants

Collaborator

Trials

16

Recruited

58,200+

Findings from Research

Technological advancements can enhance the design of acute stroke trials by optimizing dose selection, eligibility criteria, and controlling confounding factors, which may lead to more effective treatments.

While recent trials have not yet found a successful neuroprotectant, they have improved methodologies that could increase the chances of success in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in neuroprotection trials. Lees, KR.[2017]

Many acute stroke treatment trials have not shown effective results due to various design flaws, such as using inappropriate animal models and short time windows for drug delivery after a stroke occurs.

Clinical trials face challenges like the diversity of stroke causes, difficulties in measuring functional outcomes, and the small treatment effects that make it hard to determine the efficacy of new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of future acute-stroke treatment trials. Lees, KR., Hankey, GJ., Hacke, W.[2019]

Stroke is a major global health issue, with a lifetime risk of approximately 25% for adults over 25, highlighting the need for effective treatments and recovery strategies.

The review emphasizes the importance of developing precision medicine approaches through biomarker studies, which can tailor interventions based on individual stroke characteristics, potentially improving outcomes for millions of stroke survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarker Application for Precision Medicine in Stroke. Simpkins, AN., Janowski, M., Oz, HS., et al.[2022]

The ADAPT-IT project is exploring adaptive clinical trial designs to improve drug and medical device evaluations, using the ongoing SHINE trial as a case study for tight glucose control in stroke patients.

Simulations showed that the SHINE trial design has slightly higher statistical power, while the alternative Goldilocks design requires a smaller sample size, but the SHINE investigators ultimately chose not to implement the Goldilocks design for the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Stroke Hyperglycemia Insulin Network Effort (SHINE) trial: an adaptive trial design case study. Connor, JT., Broglio, KR., Durkalski, V., et al.[2018]

Personalized medicine, which tailors treatment based on individual genetic makeup and biomarker status, has the potential to enhance the effectiveness and safety of therapies for stroke patients.

This approach could revolutionize stroke care by allowing for more precise treatment selection, improving patient outcomes and addressing the variability in how patients respond to the same treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does personalized medicine exist and can you test it in a clinical trial? Sandercock, PA.[2015]

The study developed the IschAEmic Stroke Calculator, an online tool that predicts the incidence of adverse events (AEs) in acute stroke trials based on patient characteristics, using data from the Virtual International Stroke Trials Archive (VISTA).

This calculator identifies 48 common AEs and allows researchers to compare predicted incidences with observed data, aiding in the interpretation of trial safety and potentially guiding preventive measures in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Online Tool to Improve Stratification of Adverse Events in Stroke Clinical Trials. Hesse, K., MacIsaac, RL., Abdul-Rahim, AH., et al.[2021]

A comprehensive analysis of adverse events (AEs) from 5775 patients in acute ischemic stroke trials identified 132 expected AEs that accounted for 82.7% of reported events, primarily occurring within 10 days post-stroke.

Patient characteristics such as age, sex, baseline stroke severity, and multimorbidity status can modestly predict the incidence of AEs, helping to stratify patients by their risk for poststroke complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristic adverse events and their incidence among patients participating in acute ischemic stroke trials. Hesse, K., Fulton, RL., Abdul-Rahim, AH., et al.[2022]

A systematic review of 50 randomized controlled trials involving 4,779 citations found that 18 out of 28 drug interventions significantly improved motor recovery post-stroke compared to placebo, indicating potential efficacy of these treatments.

Despite the promising results, the high risk of bias in many studies raises concerns about the reliability of the findings, highlighting the need for further research to optimize drug interventions and their combination with physical therapy for better stroke recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of recovery-promoting drugs for motor function after stroke: A systematic review of randomized controlled trials. Firth, N., Barker, RN., Hayward, KS., et al.[2019]

The PROSPER study focuses on understanding stroke care from the patient's perspective, prioritizing outcomes like 'home time' and major adverse cardiovascular events, which are crucial for stroke survivors.

By analyzing the safety and effectiveness of treatments such as oral anticoagulants, statins, and antidepressants, PROSPER aims to improve decision-making in stroke care and enhance patient outcomes based on individual preferences and needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research: Implementing the patient-driven research paradigm to aid decision making in stroke care. Xian, Y., O'Brien, EC., Fonarow, GC., et al.[2022]

The study successfully randomized 984 patients with suspected acute ischaemic stroke to assess the safety and efficacy of different antithrombotic therapies, indicating that the trial design is feasible for large-scale implementation.

Results showed that within 14 days, 10% of patients died, and 3% experienced a recurrent stroke, highlighting the need for a larger trial (over 20,000 patients) to better understand the risks and benefits of early antithrombotic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study design of the International Stroke Trial (IST), baseline data, and outcome in 984 randomised patients in the pilot study. [2019]

The failure of the NXY-059 trial highlights the challenges in developing effective drugs for acute stroke, despite following established guidelines, indicating a need for a reevaluation of drug discovery strategies.

The review emphasizes the importance of collaboration among academia, government, and the pharmaceutical industry, as well as the need for improved assessment technologies and patient selection to enhance the efficacy of future stroke treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Missing steps in the STAIR case: a Translational Medicine perspective on the development of NXY-059 for treatment of acute ischemic stroke. Feuerstein, GZ., Zaleska, MM., Krams, M., et al.[2014]

A review of 126 stroke trials published between 2001 and 2006 revealed significant variability in functional outcome assessment methods, with 47 different measures used, which can affect the quality and comparability of trial results.

Only one-third of the trials provided detailed methodology for outcome assessment, highlighting the need for standardized and validated approaches to improve data quality in stroke research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional outcome measures in contemporary stroke trials. Quinn, TJ., Dawson, J., Walters, MR., et al.[2022]

Precision medicine holds great promise for stroke neurology by tailoring diagnosis, treatment, and recovery strategies to individual patients, rather than relying solely on general genetic risk assessments.

To fully realize the benefits of precision medicine in stroke, it is essential to collect and analyze diverse data from clinical trials and routine care, enabling the development of personalized therapeutic strategies based on specific diagnostic information.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Principles of precision medicine in stroke. Hinman, JD., Rost, NS., Leung, TW., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Advances in neuroprotection trials. [2017]

2. England pubmed.ncbi.nlm.nih.gov

Design of future acute-stroke treatment trials. [2019]

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

Biomarker Application for Precision Medicine in Stroke. [2022]

4. England pubmed.ncbi.nlm.nih.gov

The Stroke Hyperglycemia Insulin Network Effort (SHINE) trial: an adaptive trial design case study. [2018]

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

Does personalized medicine exist and can you test it in a clinical trial? [2015]

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

Online Tool to Improve Stratification of Adverse Events in Stroke Clinical Trials. [2021]

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

Characteristic adverse events and their incidence among patients participating in acute ischemic stroke trials. [2022]

8. Sweden pubmed.ncbi.nlm.nih.gov

Safety and efficacy of recovery-promoting drugs for motor function after stroke: A systematic review of randomized controlled trials. [2019]

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

Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research: Implementing the patient-driven research paradigm to aid decision making in stroke care. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Study design of the International Stroke Trial (IST), baseline data, and outcome in 984 randomised patients in the pilot study. [2019]

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

Missing steps in the STAIR case: a Translational Medicine perspective on the development of NXY-059 for treatment of acute ischemic stroke. [2014]

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

Functional outcome measures in contemporary stroke trials. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Principles of precision medicine in stroke. [2021]