Clinical trial NCT05797792: CHemical OptImization of Cerebral Embolectomy 2 (CHOICE 2).
Official title: CHemical OptImization of Cerebral Embolectomy in Patients with Acute Stroke Treated with Mechanical Thrombectomy 2 (CHOICE 2 TRIAL)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Stroke, Acute Ischemic
Stroke, Acute
Keywords: Mechanical Thrombectomy
Recanalization
Reperfusion
Alteplase
Lead sponsor: Hospital Clinic of Barcelona
Sponsor class: OTHER
First posted: 2023-04-04
Enrollment: 440
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, prospective, randomized, open, blinded end-point assessment phase III trial
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Modified Rankin Scale at day 90
timeFrame: 90 days post treatment
Secondary outcomes:
measure: Microvascular hypoperfusion on follow-up brain CTP
timeFrame: 36±24hours post treatment
measure: Volume of hypoperfusion on brain CTP
timeFrame: at 36h±24h post treatment
measure: Infarct Expansion Ratio (IER): Final infarct to initial ischemic tissue volumes on brain CTP
timeFrame: 36±24hours post treatment
measure: Barthel Scale score
timeFrame: day 90 post treatment
measure: EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D-3L)
timeFrame: day 90 post treatment
measure: Shift analysis of the modified Rankin Scale (mRS)
timeFrame: day 90 post treatment
Other outcomes:
measure: SAFETY OUTCOME: Mortality at 90 days
timeFrame: Day 90
measure: SAFETY OUTCOME: symptomatic intracerebral hemorrahge (sICH ) rate at 24 hours.
timeFrame: 24hours post MT
Locations:
city: Alicante
country: Spain
facility: Hospital Universitario Dr. Balmis
city: Badalona
country: Spain
facility: Hospital Germans Trías i Pujol
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Bilbao
country: Spain
facility: Hospital Universitario de Cruces
city: Coruña
country: Spain
facility: Hospital Universitario de A Coruña
city: Girona
country: Spain
facility: Hospital Josep Trueta
city: Mallorca
country: Spain
facility: Hospital Universitario Son Espases
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Pamplona
country: Spain
facility: Hospital Universitario de Navarra
city: San Sebastián
country: Spain
facility: Hospital Universitario de Donostia
city: Valencia
country: Spain
facility: Hospital Univesitario y Politénico La Fe
city: Valladolid
country: Spain
facility: Hospital Universitario de Valladolid
Study officials:
affiliation: Comprehensive Stroke Center, Hospital Clinic Barcelona
name: Angel Chamorro, MD, PhD
role: STUDY_CHAIR
affiliation: Comprehensive Stroke Center, Hospital Clinic Barcelona
name: Arturo Renú, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario de Valladolid
name: Juan F Arenillas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario de Cruces
name: María del Mar Freijo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Donostia
name: Patricia de la Riva, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario de A Coruña
name: M Dolores Fernándes, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Central de Asturias
name: Pedro Vega, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario La Fe de Valencia
name: Lluis Morales, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Germans Trias i Pujol de Badalona
name: Laura Dorado, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Dr. Josep Trueta de Girona
name: Mikel Terceño, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Virgen de Arrixaca Murcia
name: Ana Morales, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital of Navarra
name: Maria Herrera, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Son Espases Mallorca
name: Raquel Delgado, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Dr. Balmis Alicante
name: Nicolás López, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario de la Santa Creu i Sant Pau Barcelona
name: Pol Camps, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.
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.
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.
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.
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.