CHOICE2: CHemical OptImization of Cerebral Embolectomy 2 (CHOICE 2).

Sponsor

Hospital Clinic of Barcelona (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05797792

Collaborator

Instituto de Salud Carlos III (Other), Fundacion Clinic per a la Recerca Biomédica (Other)

440

Enrollment

Locations

Arms

Anticipated Duration (Months)

36.7

Patients Per Site

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Multi-center, randomized, parallel-group, superiority study to compare the efficacy of adjunct intra-arterial rt-PA versus not adjunct intra-arterial rt-PA in the improvement of the efficacy of mechanical thrombectomy in patients with large vessel occlusion acute ischemic stroke.

Condition or Disease	Intervention/Treatment	Phase
Stroke, Acute Ischemic Stroke, Acute	Drug: Intraarterial alteplase	Phase 3

Detailed Description

The study objective is to validate whether the administration of intra-arterial rt-PA is efficient as an add-on to mechanical thrombectomy in patients with acute ischemic stroke and complete or near-complete recanalization of a proximal vessel occlusion and successful brain reperfusion on cerebral angiogram (corresponding to modified treatment in cerebral infarct (mTICI) score 2b/3). Patients with symptomatic large vessel occlusion (LVO) in the anterior circulation treated with MT resulting in a mTICI score 2b/3 on cerebral angiography will be enrolled in the angiosuite by interventionalists or neurologists once a mTICI 2b/3 is confirmed on cerebral angiography. Each included patient will be followed up to 90 days from the stroke. The primary outcome is the proportion of patients with microvascular hypoperfusion on CT Perfusion at 36±24h. The key secondary outcome is the proportion of patients with a mRS 0 to 1 at 90 days

Study Design

Study Type:

Interventional

Anticipated Enrollment :

440 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Multicenter, prospective, randomized, open, blinded end-point assessment phase III trialMulticenter, prospective, randomized, open, blinded end-point assessment phase III trial

Masking:

Single (Outcomes Assessor)

Masking Description:

The evaluation of the primary outcome measure (microvascular hypoperfusion on CTP) will be conducted at the Imaging Central Core Laboratory by blinded evaluators. The evaluation of key clinical outcome at 3 months will be conducted by central blinded evaluators following a structured questionnaire of the modified Rankin Scale (mRS

Primary Purpose:

Treatment

Official Title:

CHemical OptImization of Cerebral Embolectomy in Patients With Acute Stroke Treated With Mechanical Thrombectomy 2 (CHOICE 2 TRIAL)

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2025

Anticipated Study Completion Date :

May 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intraarterial alteplase All the patients will be given a 15 minutes IA infusion of alteplase (Actylise®) at a drug concentration of 1.0 mg/ml. At 15 minutes of IA treatment onset, the infusion will be stopped and the angiographic score assessed. Study drug will be prepared according to the following steps: 1/ Dilute 2 vials of 10 mgs (rt-PA) in 20 cc of sterile water for injection (SWI), to attain a 20 ml solution at a concentration of 1mg/ml; 2. Calculate the volume of cc of infusion and therefore the total dose as per the formula: (Patient's weight in Kgs multiplied by 0.225). A patient of 89 Kgs or more will receive 20.0 cc of infusion for 15 min, totaling a dose of 20.0 mg of rt-PA.	Drug: Intraarterial alteplase See arm/group descriptions. Other Names: Intraarterial recombinant tissue plasminogen activator (rt-PA)
No Intervention: No intervention Patients allocated to this arm will receive a similar care to patients allocated to IA alteplase except the thrombolytic

Arm

Intervention/Treatment

Experimental: Intraarterial alteplase

All the patients will be given a 15 minutes IA infusion of alteplase (Actylise®) at a drug concentration of 1.0 mg/ml. At 15 minutes of IA treatment onset, the infusion will be stopped and the angiographic score assessed. Study drug will be prepared according to the following steps: 1/ Dilute 2 vials of 10 mgs (rt-PA) in 20 cc of sterile water for injection (SWI), to attain a 20 ml solution at a concentration of 1mg/ml; 2. Calculate the volume of cc of infusion and therefore the total dose as per the formula: (Patient's weight in Kgs multiplied by 0.225). A patient of 89 Kgs or more will receive 20.0 cc of infusion for 15 min, totaling a dose of 20.0 mg of rt-PA.

Drug: Intraarterial alteplase

See arm/group descriptions.

Other Names:

Intraarterial recombinant tissue plasminogen activator (rt-PA)

No Intervention: No intervention

Patients allocated to this arm will receive a similar care to patients allocated to IA alteplase except the thrombolytic

Outcome Measures

Primary Outcome Measures

Microvascular hypoperfusion on brain CT Perfusion [36±24hours post treatment]
Proportion of patients with abnormal microvascular hypoperfusion on brain CTPerfusion at 36±24hours post Mechanical Thrombectomy.

Secondary Outcome Measures

modified Rankin Scale (mRS) score [90 days post MT]
Proportion of patients with a mRS 0 to 1 (min value 0, max value 6, higher score worse outcome)
Volume of microvascular hypoperfusion on follow-up brain CTP [36±24hours post treatment]
Volume of hypoperfusion on brain CTP at 36h±24hours post MT
Infarct Expansion Ratio (IER): Final infarct to initial ischemic tissue volumes on brain CTP [36±24hours post treatment]
Infarct Expansion Ratio (IER): Final infarct to initial ischemic tissue volumes on brain CTP at 36±24hours post MT.
Barthel Scale score [day 90 post treatment]
Barthel Scale score of 95 to 100, (min value 0, max value 100, higher score better outcome)
EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D-3L) [day 90 post treatment]
Quality of life measured with the EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D-3L) The score has five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems.
Shift analysis of the modified Rankin Scale (mRS) [day 90 post treatment]
Shift analysis of the modified Rankin Scale (mRS), at day 90 (min value 0, max value 6, higher score worse outcome)

Other Outcome Measures

SAFETY OUTCOME: Mortality at 90 days [Day 90]
Mortality at 90 days
SAFETY OUTCOME: symptomatic intracerebral hemorrahge (sICH ) rate at 24 hours. [24hours post MT]
Symptomatic ICH will be classified as per the European Cooperative Acute Stroke Study (ECASS) 3 criteria

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with symptomatic large vessel occlusion (LVO) in the anterior circulation (ICA, ACA or MCA) treated with MT resulting in a mTICI score 2b/3 at end of the procedure. Patients with a mTICI score 2b/3 on the diagnostic cerebral angiography before the onset of MT are also eligible for the study.
Estimated delay to onset of rescue intraarterial 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 instead of NCCT, especially if >9h have elapsed, or in seriously ill patients (i.e., NIHSS>17). Nonetheless, if a perfusion study is not available, NCCT can still be used as long as it is confirmed without a doubt that the ASPECTS is > 6.
Informed consent, obtained from patient or acceptable patient surrogate, or Differed Informed Consent (DIC) to avoid any delay in the initiation of the mechanical thrombectomy and the i.a thrombolysis. The DIC will be signed by the patient or acceptable patient surrogate at any time after the tPA treatment is started.

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, 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)

Contacts and Locations

Locations

	Site	City	Country
1	Hospital Germans Trías i Pujol	Badalona	Spain
2	Hospital Clinic Barcelona	Barcelona	Spain
3	Hospital de la Santa Creu i Sant Pau	Barcelona	Spain
4	Hospital del Mar	Barcelona	Spain
5	Hospital Universitario de Cruces	Bilbao	Spain
6	Hospital Universitario de A Coruña	Coruña	Spain
7	Hospital Josep Trueta	Girona	Spain
8	Hospital Universitario Virgen de la Arrixaca	Murcia	Spain
9	Hospital Universitario Central de Asturias	Oviedo	Spain
10	Hospital Universitario de Donostia	San Sebastián	Spain
11	Hospital Univesitario y Politénico La Fe	Valencia	Spain
12	Hospital Universitario de Valladolid	Valladolid	Spain

Sponsors and Collaborators

Hospital Clinic of Barcelona
Instituto de Salud Carlos III
Fundacion Clinic per a la Recerca Biomédica

Investigators

Study Chair: Angel Chamorro, MD, Comprehensive Stroke Center, Hospital Clinic Barcelona
Principal Investigator: Arturo Renú, MD, Comprehensive Stroke Center, Hospital Clinic Barcelona
Principal Investigator: Juan F Arenillas, MD, Hospital Universitario de Valladolid
Principal Investigator: María del Mar Freijo, MD, Hospital Universitario de Cruces
Principal Investigator: Maite Alonso, MD, Hospital Universitario de Donostia
Principal Investigator: María D Fernandez, MD, Hospital Universitario de A Coruña
Principal Investigator: Pedro Vega, MD, Hospital Universitario Central de Asturias
Principal Investigator: Lluis Morales, MD, Hospital Univesitario y Politénico La Fe
Principal Investigator: Laura Dorado, MD, Hospital Germans Trías i Pujol
Principal Investigator: Pol Camps, MD, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Principal Investigator: Mikel Terceño, MD, Hospital Josep Trueta
Principal Investigator: Ana Morales, MD, Hospital Universitario Virgen de la Arrixaca
Principal Investigator: Elisa Cuadrado, MD, Hospital del Mar