- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03876119
Intraarterial Alteplase Versus Placebo After Mechanical Thrombectomy (CHOICE)
CHemical OptImization of Cerebral Embolectomy in Patients With Acute Stroke Treated With Mechanical Thrombectomy (CHOICE) Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The study objective is to evaluate whether rt-PA is safe and 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 mTICI score 2b/3) The study is a multicenter, randomized, placebo-controlled, double blind, phase 2b trial of acute stroke patients treated with MT, in which two therapies are compared: rt-PA or placebo. Allocation at each center will account for 1 stratum: use of alteplase (yes vs. no) before MT. Subjects will be followed up to 90 days post-randomization
Patients will be enrolled in the angiosuit by interventionalists or neurologists once a mTICI 2b/3 is confirmed on cerebral angiography. The primary outcome is the proportion of patients with a mRS 0 to 1 at 90 days. A sample size of 100 patients per treatment arm in a 1:1 allocation will have at least 80% statistical power for the primary outcome (mRS with 0-1 score values) assuming a rate of 40% in the control arm and a 21% benefit in the experimental arm (odds ratio (OR) of 2.33) for a 5% two-sided type I error. This sample size will also guarantee the study power for that relative treatment benefit even if the success rate in the control group rises up to ≈56%. No study losses are accounted for since all randomised patients will be included in the analysis.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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Badalona, Spain
- Germans Trias I Pujol Hospital
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Barcelona, Spain
- Hospital Universitari Vall d'Hebrón
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Barcelona, Spain, 08036
- Hospital Clinic of Barcelona
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Barcelona, Spain
- Hospital Universitari de Bellvitge
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Barcelona, Spain, 08036
- Hospital del Mar
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Barcelona, Spain
- Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
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Girona, Spain, 17007
- Hospital Josep Trueta (HJT)
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
INCLUSION CRITERIA:
- Patients with symptomatic large vessel occlusion (LVO) in the anterior, middle or posterior cerebral artery treated with MT resulting in an mTICI score 2b/3 at end of the procedure.. Patients with an 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 or MRI if symptoms lasting <4.5 hours or ASPECTS >6 on CT-Perfusion (CTP) or DWI-MRI if symptoms >4.5 <24 hours.
- Informed consent obtained from patient or acceptable patient surrogate
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
- 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 (except observational study i.e.: RACECAT or clinical trials not testing new medical devices or new drugs i.e.IMAGECAT)
- Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency
- Known coagulopathy, INR > 1.7 or use of novel anticoagulants < 48h from symptom onset
- 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 (e.g. no fixed home address, visitor from overseas)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / 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. If the angiographic score is improved compared with the baseline score the procedure is terminated, otherwise a new angiographic series will be repeated in 10 minutes before the end of the procedure in front and profile projections. Study drug will be prepared according to the following steps:
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See arm/group descriptions.
Other Names:
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Placebo Comparator: Placebo
The placebo will consist of a lyophilized white powder containing 0.2 mol/L arginine phosphate, 0.01% polysorbate 80, and pH 7.4 after reconstitution. Study drug will be prepared according to the following steps:
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See arm/group descriptions.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Good outcome at 90 days
Time Frame: Day 90 after treatment.
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The primary outcome will be the proportion of patients with a mRS 0 to 1 at 90 days
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Day 90 after treatment.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Shift analysis of the 90-day modified Rankin Scale (mRS).
Time Frame: Day 90 after treatment.
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The shift analysis of the modified Rankin Scale (mRS), at day 90.
The mRS at 90 days will be analyzed using a proportional odds model (POM) that combine into single worst rank the last two categories (5: severe incapacity and 6: death).
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Day 90 after treatment.
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Infarct expansion ratio.
Time Frame: 48 (+/- 24h) hours of stroke
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Infarct Expansion Ratio on DWI-MRI (continuous variable), at 48h (+/- 24h) of stroke
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48 (+/- 24h) hours of stroke
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Rate of infarct expansion at 24 hours.
Time Frame: 48 (+/- 24h) hours of stroke
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Proportion of patients with/without infarct expansion (dichotomous variable).
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48 (+/- 24h) hours of stroke
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Final infarct volume.
Time Frame: 48 (+/- 24h) hours of stroke
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Infarction Volume on Diffusion Weighted Imaging (Magnetic Resonance Imaging) at 48h (+/- 24h) of stroke onset
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48 (+/- 24h) hours of stroke
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Angiographic improvement on the Arterial Occlusive Lesion (AOL) scale
Time Frame: 10 minutes after treatment
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Proportion of patients with angiographic improvement on the Arterial Occlusive Lesion (AOL) scale.
AOL describes arterial patency at the site of occlusion based on the degree of luminal opening (none, partial, or complete) with further qualification based simply on the presence (grades 2 or 3) or absence (grades 0 or 1) of any downstream flow.
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10 minutes after treatment
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TERTIARY OUTCOME: Barthel Scale at day 90
Time Frame: Day 90 after treatment.
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Barthel Scale score of 95 to 100, at day 90
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Day 90 after treatment.
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TERTIARY OUTCOME: Ischemic worsening within 72 hours os stroke onset
Time Frame: 72 hours of stroke onset
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Ischemic worsening (≥ 4 points in the NIHSS score) within 72 hours of stroke onset not attributable to stroke recurrence
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72 hours of stroke onset
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TERTIARY OUTCOME: Quality of life measured at 90 days
Time Frame: Day 90 after treatment.
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Quality of life measured with the EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D-3L) at 90 days
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Day 90 after treatment.
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of patients with improved mTICI 2b score
Time Frame: 10 minutes after treatment
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Proportion of patients with improved mTICI 2b score
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10 minutes after treatment
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Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Angel Chamorro, MD, PhD, Comprehensive Stroke Center, Hospital Clinic Barcelona.
- Principal Investigator: Arturo Renú, MD, PhD, Comprehensive Stroke Center, Hospital Clinic Barcelona.
- Principal Investigator: Marián Muchada, MD, PhD, Hospital Universitario de Vall d'Hebrón
- Principal Investigator: Elisa Cuadrado, MD, PhD, Hospital del Mar
- Principal Investigator: Anna Ramos, MD, Germans Trias I Pujol Hospital
- Principal Investigator: Pol Camps, MD, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
- Principal Investigator: Pere Cardona, MD, PhD, Hospital Universitari de Bellvitge
- Principal Investigator: Mikel Terceño, MD, Hospital Josep Trueta, Girona
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CHOICE
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
- Clinical Study Report (CSR)
- Analytic Code
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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