CHemical OptImization of Cerebral Embolectomy 2 (CHOICE 2).

NCT ID: NCT05797792

Last Updated: 2025-09-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 440 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-18
• Study Completion Date: 2025-11-14

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.

Conditions

Stroke, Acute Ischemic; Stroke, Acute

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Intraarterial alteplase

Intervention Type: DRUG

See arm/group descriptions.

No intervention

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Intraarterial alteplase

See arm/group descriptions.

Intervention Type: DRUG

Other Intervention Names

Intraarterial recombinant tissue plasminogen activator (rt-PA)

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Clinic of Barcelona

OTHER

Sponsor Role: lead

Responsible Party

Angel Chamorro, M.D., Ph.D.

Director, Comprehensive Stroke Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Angel Chamorro, MD, PhD

Role: STUDY_CHAIR

Comprehensive Stroke Center, Hospital Clinic Barcelona

Arturo Renú, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Comprehensive Stroke Center, Hospital Clinic Barcelona

Juan F Arenillas, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario de Valladolid

María del Mar Freijo, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario de Cruces

Patricia de la Riva, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Donostia

M Dolores Fernándes, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario de A Coruña

Pedro Vega, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Central de Asturias

Lluis Morales, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario La Fe de Valencia

Laura Dorado, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Germans Trias i Pujol de Badalona

Mikel Terceño, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Dr. Josep Trueta de Girona

Ana Morales, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Virgen de Arrixaca Murcia

Maria Herrera, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital of Navarra

Raquel Delgado, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Son Espases Mallorca

Nicolás López, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Dr. Balmis Alicante

Pol Camps, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario de la Santa Creu i Sant Pau Barcelona

Locations

Hospital Universitario de A Coruña

A Coruña, Spain, Spain

Hospital Universitario Dr. Balmis

Alicante, Spain, Spain

Hospital Germans Trías i Pujol

Badalona, Spain, Spain

Hospital Clinic Barcelona

Barcelona, Spain, Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain, Spain

Hospital Universitario de Cruces

Bilbao, Spain, Spain

Hospital Josep Trueta

Girona, Spain, Spain

Hospital Universitario Virgen de la Arrixaca

Murcia, Spain, Spain

Hospital Universitario Central de Asturias

Oviedo, Spain, Spain

Hospital Universitario Son Espases

Palma de Mallorca, Spain, Spain

Hospital Universitario de Navarra

Pamplona, Spain, Spain

Hospital Universitario de Donostia

San Sebastián, Spain, Spain

Hospital Univesitario y Politénico La Fe

Valencia, Spain, Spain

Hospital Universitario de Valladolid

Valladolid, Spain, Spain

Countries

Spain

References

Chamorro A, Blasco J, Lopez A, Amaro S, Roman LS, Llull L, Renu A, Rudilosso S, Laredo C, Obach V, Urra X, Planas AM, Leira EC, Macho J. Complete reperfusion is required for maximal benefits of mechanical thrombectomy in stroke patients. Sci Rep. 2017 Sep 14;7(1):11636. doi: 10.1038/s41598-017-11946-y.

Reference Type: BACKGROUND

PMID: 28912596 (View on PubMed)

Davalos A, Cobo E, Molina CA, Chamorro A, de Miquel MA, Roman LS, Serena J, Lopez-Cancio E, Ribo M, Millan M, Urra X, Cardona P, Tomasello A, Castano C, Blasco J, Aja L, Rubiera M, Gomis M, Renu A, Lara B, Marti-Fabregas J, Jankowitz B, Cerda N, Jovin TG; REVASCAT Trial Investigators. Safety and efficacy of thrombectomy in acute ischaemic stroke (REVASCAT): 1-year follow-up of a randomised open-label trial. Lancet Neurol. 2017 May;16(5):369-376. doi: 10.1016/S1474-4422(17)30047-9. Epub 2017 Mar 16.

Reference Type: BACKGROUND

PMID: 28318984 (View on PubMed)

Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, San Roman L, Serena J, Abilleira S, Ribo M, Millan M, Urra X, Cardona P, Lopez-Cancio E, Tomasello A, Castano C, Blasco J, Aja L, Dorado L, Quesada H, Rubiera M, Hernandez-Perez M, Goyal M, Demchuk AM, von Kummer R, Gallofre M, Davalos A; REVASCAT Trial Investigators. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015 Jun 11;372(24):2296-306. doi: 10.1056/NEJMoa1503780. Epub 2015 Apr 17.

Reference Type: BACKGROUND

PMID: 25882510 (View on PubMed)

Renu A, Blasco J, Millan M, Marti-Fabregas J, Cardona P, Oleaga L, Macho J, Molina C, Roquer J, Amaro S, Davalos A, Zarco F, Laredo C, Tomasello A, Guimaraens L, Barranco R, Castano C, Vivas E, Ramos A, Lopez-Rueda A, Urra X, Muchada M, Cuadrado-Godia E, Camps-Renom P, Roman LS, Rios J, Leira EC, Jovin T, Torres F, Chamorro A; CHOICE Investigators. The Chemical Optimization of Cerebral Embolectomy trial: Study protocol. Int J Stroke. 2021 Jan;16(1):110-116. doi: 10.1177/1747493019895656. Epub 2019 Dec 18.

Reference Type: BACKGROUND

PMID: 31852410 (View on PubMed)

Renu A, Millan M, San Roman L, Blasco J, Marti-Fabregas J, Terceno M, Amaro S, Serena J, Urra X, Laredo C, Barranco R, Camps-Renom P, Zarco F, Oleaga L, Cardona P, Castano C, Macho J, Cuadrado-Godia E, Vivas E, Lopez-Rueda A, Guimaraens L, Ramos-Pachon A, Roquer J, Muchada M, Tomasello A, Davalos A, Torres F, Chamorro A; CHOICE Investigators. Effect of Intra-arterial Alteplase vs Placebo Following Successful Thrombectomy on Functional Outcomes in Patients With Large Vessel Occlusion Acute Ischemic Stroke: The CHOICE Randomized Clinical Trial. JAMA. 2022 Mar 1;327(9):826-835. doi: 10.1001/jama.2022.1645.

Reference Type: BACKGROUND

PMID: 35143603 (View on PubMed)

Laredo C, Rodriguez A, Oleaga L, Hernandez-Perez M, Renu A, Puig J, Roman LS, Planas AM, Urra X, Chamorro A. Adjunct Thrombolysis Enhances Brain Reperfusion following Successful Thrombectomy. Ann Neurol. 2022 Nov;92(5):860-870. doi: 10.1002/ana.26474. Epub 2022 Aug 23.

Reference Type: BACKGROUND

PMID: 36054449 (View on PubMed)

Chamorro A, Torres F. Intra-arterial Alteplase vs Placebo After Successful Thrombectomy and Functional Outcomes in Patients With Large Vessel Occlusion Acute Ischemic Stroke-Reply. JAMA. 2022 Jun 28;327(24):2456. doi: 10.1001/jama.2022.7430. No abstract available.

Reference Type: BACKGROUND

PMID: 35763000 (View on PubMed)

Other Identifiers

2023-504262-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CHOICE 2

Identifier Type: -

Identifier Source: org_study_id