Evaluation of Alteplase as an Adjunct to Mechanical Thrombectomy in Acute Ischemic Stroke with Proximal Vessel Recanalization
- Trial ID
- 2023-504262-32-01
- Protocol
- CHOICE2
Trial statistics
Diseases & Conditions
Objectives
The primary objective of the CHOICE2TRIAL is to evaluate the efficacy of **rt-PA** (alteplase) as an adjunctive treatment to mechanical thrombectomy in patients with acute ischemic stroke. This study specifically targets individuals who have achieved recanalization with complete or near-complete reperfusion of a proximal vessel occlusion, as indicated by a modified Thrombolysis in Cerebral Infarction (mTICI) score of 2b/3 on cerebral angiogram. The clinical relevance of this objective lies in determining whether the addition of rt-PA can enhance outcomes in terms of reperfusion quality and neurological recovery, potentially leading to improved therapeutic strategies for acute ischemic stroke management.
Participants
The clinical trial involves participants diagnosed with **acute ischemic stroke** undergoing cerebral embolectomy. The study population includes both male and female subjects, aged 18 years and older, with no significant pre-stroke functional disability. The trial does not involve a vulnerable population. Participants were selected based on specific criteria, including symptomatic large vessel occlusion in the anterior circulation and a modified Thrombolysis in Cerebral Infarction (mTICI) angiographic score of 2b/3 at the end of the mechanical thrombectomy procedure. The trial population was chosen to ensure that participants had an ASPECTS score of 6 or higher on a non-contrast CT scan if symptoms lasted less than 4.5 hours from the last time they were seen well. For those with symptoms lasting more than 4.5 hours, additional imaging such as CT-perfusion or MRI-perfusion was considered. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet and physical activity were not specified as part of the selection criteria. Informed consent was obtained from all participants or their acceptable surrogates.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **alteplase** as an adjunct to mechanical thrombectomy in patients with acute ischemic stroke. This study employs a randomized, double-blind, controlled methodology to ensure the reliability and validity of the results. The trial is categorized as a low-intervention study, with the use of intra-arterial alteplase being common in clinical practice, supported by existing scientific evidence. The trial is expected to commence on October 10, 2023, and conclude by November 30, 2025, with the primary endpoint being the proportion of patients achieving a modified Rankin Scale (mRS) score of 0 to 1 at 90 days post-treatment.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as symptomatic large vessel occlusion in the anterior circulation and an mTICI angiographic score of 2b/3 post-procedure. The estimated delay to the onset of rescue intra-arterial alteplase administration must be less than 24 hours from symptom onset. Follow-up visits will be conducted to assess secondary endpoints, including the proportion of patients with abnormal microvascular hypoperfusion on CT Perfusion at 36±24 hours post-mechanical thrombectomy, and the volume of hypoperfusion on brain CTP at the same time point. The end-of-study visit will occur at 90 days, where the Barthel Scale score and quality of life, measured with the EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D-5L), will be evaluated.
Participant involvement is expected to last approximately 90 days, with conditions for early termination including significant adverse events or withdrawal of consent. The trial aims to provide robust data on the effectiveness of alteplase in enhancing outcomes for patients undergoing mechanical thrombectomy for acute ischemic stroke.
Treatment
The clinical trial involves the use of the experimental medication **Actilyse**, which is a **solution for injection/infusion**. The active substance in Actilyse is **alteplase**, a recombinant tissue plasminogen activator (rt-PA). This medication is provided in the form of a powder and solvent for solution, intended for intraarterial use. The maximum daily dose of alteplase is 20 mg, with a total maximum dose of 20 mg over a treatment period of one day. The administration of Actilyse is conducted via intraarterial route, which is specifically chosen for its targeted delivery in the context of acute ischemic stroke treatment. The pharmaceutical form and administration route are designed to optimize the therapeutic effect of alteplase in achieving recanalization and reperfusion in patients undergoing mechanical thrombectomy.
In this study, Actilyse is used as an add-on treatment to mechanical thrombectomy in patients with acute ischemic stroke. The trial aims to evaluate the efficacy of rt-PA in enhancing the outcomes of mechanical thrombectomy, particularly in cases where there is complete or near-complete reperfusion of a proximal vessel occlusion, as indicated by a modified Thrombolysis in Cerebral Infarction (mTICI) score of 2b/3. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial protocol. Participant compliance with the dosing schedule is monitored to ensure adherence to the treatment regimen and to assess the safety and efficacy of the experimental medication.
Efficacy
Efficacy in the clinical trial titled "CHemical OptImization of Cerebral Embolectomy in patients with acute stroke treated with mechanical thrombectomy 2 (CHOICE2TRIAL)" will be assessed using both primary and secondary endpoints. The primary endpoint is the proportion of patients achieving a modified Rankin Scale (mRS) score of 0 to 1 at 90 days post-treatment, indicating minimal or no disability. Secondary endpoints include the proportion of patients with abnormal microvascular hypoperfusion on CT Perfusion at 36±24 hours post mechanical thrombectomy (MT), the volume of hypoperfusion on brain CTP at the same timepoint, and the Infarct Expansion Ratio (IER), which compares final infarct to initial ischemic tissue volumes on brain NCCT at 36±24 hours post MT. Additional secondary endpoints include the Barthel Scale score of 95 to 100 at day 90, quality of life measured with the EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D-5L) at 90 days, and the shift analysis of the modified Rankin Scale (mRS) at day 90.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patients with symptomatic large vessel occlusion (LVO) in the anterior circulation (TICA, ACA or MCA) treated with MT resulting in a mTICI angiographic score 2b/3 at end of the procedure.
- Estimated delay to onset of rescue IA rt-PA administration <24 hours from symptom onset, defined as the point in time the patient was last seen well.
- No significant pre-stroke functional disability (modified Rankin scale 0-1, or mRS >1 that according to the investigator is not related to neurological disease (i.e. amputation, blindness))
- Age ≥18
- ASPECTS ≥6 on non-contrast CT (NCCT) scan if symptoms lasting <4.5 hours of last seen well. In patients with >4.5h of last seen well, a CT-perfusion (Flow maps) or MRI-perfusion should be considered, especially if >9h have elapsed, or in seriously ill patients (i.e., NIHSS>17). If a perfusion study is not available before MT, NCCT can still be used if the ASPECTS is ≥ 6.
- Informed consent obtained from patient or acceptable patient surrogate.
Exclusion Criteria
- NIHSS score on admission >25
- Contraindication to IV t‐PA as per local national guidelines (except time to therapy)
- Use of carotid artery stents during the endovascular procedure requiring dual antiplatelet therapy during the first 24h
- Need of more than 3 passes (per vessel) or more than a total of 5 passes (in more than one vessel) to complete the endovascular procedure
- Female who is pregnant or lactating or has a positive pregnancy test at time of admission
- Current participation in another investigation drug or device treatment study
- Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency
- Known coagulopathy, or INR > 1.7
- Platelets < 50,000
- Renal Failure as defined by a serum creatinine > 3.0 mg/dl (or 265.2 μmol/l) or glomerular Filtration Rate [GFR] < 30
- Subject who requires hemodialysis or peritoneal dialysis, or who have a contraindication to an angiogram for whatever reason
- Any hemorrhage on CT/MRI
- Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT or MRI scan is normal
- Suspicion of aortic dissection
- Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol
- History of life-threatening allergy (more than rash) to contrast medium
- SBP >185 mmHg or DBP >110 mmHg refractory to treatment
- Serious, advanced, terminal illness with anticipated life expectancy < 6 months
- Pre-existing neurological or psychiatric disease that would confound evaluation
- Presumed vasculitis or septic embolization
- Unlikely to be available for 90-day follow-up (i.e., no fixed home address, visitor from overseas)
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Recruiting | 10 Oct 2023 | 440 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Actilyse, polvo y disolvente para solución inyectable y para perfusión | Test | POLVO Y DISOLVENTE PARA SOLUCIÓN INYECTABLE Y PARA PERFUSIÓN | INTRAARTERIAL USE | 20 | 1 | PRD297769 |