CHemical OptImization of Cerebral Embolectomy 2 (CHOICE 2).

NCT05797792 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: CHOICE 22023-504262-32
• Study Type: interventional
• Target: 440
• Locations: 1 country
• Sites: 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

Keywords

Mechanical Thrombectomy; Recanalization; Reperfusion; Alteplase

Outcome Measures

Primary Outcomes (1)

• Modified Rankin Scale at day 90

  Proportion of patients with Modified Rankin Scale 0 or 1 at day 90 +/- 15d

  90 days post treatment

Secondary Outcomes (6)

• Microvascular hypoperfusion on follow-up brain CTP

  36±24hours post treatment

• Volume of hypoperfusion on brain CTP

  at 36h±24h post treatment

• Infarct Expansion Ratio (IER): Final infarct to initial ischemic tissue volumes on brain CTP

  36±24hours post treatment

• Barthel Scale score

  day 90 post treatment

• EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D-3L)

  day 90 post treatment

Other Outcomes (2)

• SAFETY OUTCOME: Mortality at 90 days

  Day 90

• SAFETY OUTCOME: symptomatic intracerebral hemorrahge (sICH ) rate at 24 hours.

  24hours post MT

Study Arms (2)

Intraarterial alteplase

EXPERIMENTAL

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

No intervention

NO INTERVENTION

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

Interventions

Intraarterial alteplase DRUG

See arm/group descriptions.

Also known as: Intraarterial recombinant tissue plasminogen activator (rt-PA)

Intraarterial alteplase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospital Clinic of Barcelona: lead

Study Sites (14)

Hospital Universitario de A Coruña

A Coruña, Spain, Spain

Location

Hospital Universitario Dr. Balmis

Alicante, Spain, Spain

Location

Hospital Germans Trías i Pujol

Badalona, Spain, Spain

Location

Hospital Clinic Barcelona

Barcelona, Spain, 08014, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain, Spain

Location

Hospital Universitario de Cruces

Bilbao, Spain, Spain

Location

Hospital Josep Trueta

Girona, Spain, Spain

Location

Hospital Universitario Virgen de la Arrixaca

Murcia, Spain, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Spain, Spain

Location

Hospital Universitario Son Espases

Palma de Mallorca, Spain, Spain

Location

Hospital Universitario de Navarra

Pamplona, Spain, Spain

Location

Hospital Universitario de Donostia

San Sebastián, Spain, Spain

Location

Hospital Univesitario y Politénico La Fe

Valencia, Spain, Spain

Location

Hospital Universitario de Valladolid

Valladolid, Spain, Spain

Location

Related Publications (7)

• 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.

  PMID: 28912596 BACKGROUND

• 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.

  PMID: 28318984 BACKGROUND

• 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.

  PMID: 25882510 BACKGROUND

• 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.

  PMID: 31852410 BACKGROUND

• 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.

  PMID: 35143603 BACKGROUND

• 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.

  PMID: 36054449 BACKGROUND

• 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.

  PMID: 35763000 BACKGROUND

MeSH Terms

Conditions

Ischemic Stroke; Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Angel Chamorro, MD, PhD

  Comprehensive Stroke Center, Hospital Clinic Barcelona

  STUDY CHAIR

• Arturo Renú, MD, PhD

  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

• Patricia de la Riva, MD

  Hospital Donostia

  PRINCIPAL INVESTIGATOR

• M Dolores Fernándes, MD

  Hospital Universitario de A Coruña

  PRINCIPAL INVESTIGATOR

• Pedro Vega, MD

  Hospital Universitario Central de Asturias

  PRINCIPAL INVESTIGATOR

• Lluis Morales, MD

  Hospital Universitario La Fe de Valencia

  PRINCIPAL INVESTIGATOR

• Laura Dorado, MD

  Hospital Germans Trias i Pujol de Badalona

  PRINCIPAL INVESTIGATOR

• Mikel Terceño, MD

  Hospital Universitario Dr. Josep Trueta de Girona

  PRINCIPAL INVESTIGATOR

• Ana Morales, MD

  Hospital Universitario Virgen de Arrixaca Murcia

  PRINCIPAL INVESTIGATOR

• Maria Herrera, MD

  Hospital of Navarra

  PRINCIPAL INVESTIGATOR

• Raquel Delgado, MD

  Hospital Universitario Son Espases Mallorca

  PRINCIPAL INVESTIGATOR

• Nicolás López, MD

  Hospital Universitario Dr. Balmis Alicante

  PRINCIPAL INVESTIGATOR

• Pol Camps, MD

  Hospital Universitario de la Santa Creu i Sant Pau Barcelona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The evaluation of the primary outcome measure (modified Rankin Scale Score 0-1 at day 90) will be conducted by central blinded evaluators following a structured questionnaire. The evaluation of imaging outcome measures will be conducted at the Imaging Central Core Laboratory by blinded evaluators
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Comprehensive Stroke Center

Model Details: Multicenter, prospective, randomized, open, blinded end-point assessment phase III trial

Study Record Dates

• First Submitted: March 9, 2023
• First Posted: April 4, 2023
• Study Start: November 18, 2023
• Primary Completion: August 26, 2025
• Study Completion: November 14, 2025
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The data will become available after publication of main study results.
• Access Criteria: The IPD will be available from the Sponsor of the trial on reasonable request.

Locations

ES (14)