CHemical OptImization of Cerebral Embolectomy 2 (CHOICE 2).

Stroke, Acute Clinical Trial

— CHOICE2  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05797792
• Other study ID #: CHOICE 2
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 1, 2023
• Est. completion date: May 1, 2025

Study information

• Verified date: March 2023
• Source: Hospital Clinic of Barcelona
• Contact: Martha Vargas, PhD
• Phone: 0034-93 227 54 00
• Email: mvargas[@]clinic.cat
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 440
• Est. completion date: May 1, 2025
• Est. primary completion date: March 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Ischemic Stroke
• Stroke
• Stroke, Acute

Intervention

Drug:
• Intraarterial alteplase
See arm/group descriptions.

Locations

Country	Name	City	State
Spain	Hospital Germans Trías i Pujol	Badalona
Spain	Hospital Clinic Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario de Cruces	Bilbao
Spain	Hospital Universitario de A Coruña	Coruña
Spain	Hospital Josep Trueta	Girona
Spain	Hospital Universitario Virgen de la Arrixaca	Murcia
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	Hospital Universitario de Donostia	San Sebastián
Spain	Hospital Univesitario y Politénico La Fe	Valencia
Spain	Hospital Universitario de Valladolid	Valladolid

Sponsors (3)

Lead Sponsor	Collaborator
Hospital Clinic of Barcelona	Fundacion Clinic per a la Recerca Biomédica, Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

References & 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	SAFETY OUTCOME: Mortality at 90 days	Mortality at 90 days	Day 90
Other	SAFETY OUTCOME: symptomatic intracerebral hemorrahge (sICH ) rate at 24 hours.	Symptomatic ICH will be classified as per the European Cooperative Acute Stroke Study (ECASS) 3 criteria	24hours post MT
Primary	Microvascular hypoperfusion on brain CT Perfusion	Proportion of patients with abnormal microvascular hypoperfusion on brain CTPerfusion at 36±24hours post Mechanical Thrombectomy.	36±24hours post treatment
Secondary	modified Rankin Scale (mRS) score	Proportion of patients with a mRS 0 to 1 (min value 0, max value 6, higher score worse outcome)	90 days post MT
Secondary	Volume of microvascular hypoperfusion on follow-up brain CTP	Volume of hypoperfusion on brain CTP at 36h±24hours post MT	36±24hours post treatment
Secondary	Infarct Expansion Ratio (IER): Final infarct to initial ischemic tissue volumes on brain CTP	Infarct Expansion Ratio (IER): Final infarct to initial ischemic tissue volumes on brain CTP at 36±24hours post MT.	36±24hours post treatment
Secondary	Barthel Scale score	Barthel Scale score of 95 to 100, (min value 0, max value 100, higher score better outcome)	day 90 post treatment
Secondary	EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D-3L)	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.	day 90 post treatment
Secondary	Shift analysis of the modified Rankin Scale (mRS)	Shift analysis of the modified Rankin Scale (mRS), at day 90 (min value 0, max value 6, higher score worse outcome)	day 90 post treatment