Intraarterial Alteplase Versus Placebo After Mechanical Thrombectomy (CHOICE)

May 16, 2022 updated by: Angel Chamorro, M.D., Ph.D., Hospital Clinic of Barcelona

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

Multicenter, randomized, placebo-controlled, double blind, phase 2b trial of acute stroke patients treated with mechanical thrombectomy (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.

Study Overview

Status

Completed

Conditions

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

Interventional

Enrollment (Actual)

121

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Badalona, Spain
        • Germans Trias I Pujol Hospital
      • Barcelona, Spain
        • Hospital Universitari Vall d'Hebrón
      • Barcelona, Spain, 08036
        • Hospital Clinic of Barcelona
      • Barcelona, Spain
        • Hospital Universitari de Bellvitge
      • Barcelona, Spain, 08036
        • Hospital del Mar
      • Barcelona, Spain
        • Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
      • Girona, Spain, 17007
        • Hospital Josep Trueta (HJT)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

INCLUSION CRITERIA:

  1. 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.
  2. 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
  3. 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)
  4. Age ≥18
  5. 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.
  6. Informed consent obtained from patient or acceptable patient surrogate

EXCLUSION CRITERIA:

  1. NIHSS score on admission >25
  2. Contraindication to IV t-PA as per local national guidelines (except time to therapy)
  3. Use of carotid artery stents during the endovascular procedure requiring dual antiplatelet therapy during the first 24h
  4. Female who is pregnant or lactating or has a positive pregnancy test at time of admission
  5. 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)
  6. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency
  7. Known coagulopathy, INR > 1.7 or use of novel anticoagulants < 48h from symptom onset
  8. Platelets < 50,000
  9. Renal Failure as defined by a serum creatinine > 3.0 mg/dl (or 265.2 μmol/l) or glomerular Filtration Rate [GFR] < 30
  10. Subject who requires hemodialysis or peritoneal dialysis, or who have a contraindication to an angiogram for whatever reason
  11. Any hemorrhage on CT/MRI
  12. Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT or MRI scan is normal
  13. Suspicion of aortic dissection
  14. Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol
  15. History of life threatening allergy (more than rash) to contrast medium
  16. SBP >185 mmHg or DBP >110 mmHg refractory to treatment
  17. Serious, advanced, terminal illness with anticipated life expectancy < 6 months
  18. Pre-existing neurological or psychiatric disease that would confound evaluation
  19. Presumed vasculitis or septic embolization
  20. Unlikely to be available for 90-day follow-up (e.g. no fixed home address, visitor from overseas)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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:

  1. Dilute 3 vials of 10 mgs (alteplase) in 30 cc of sterile water for injection (SWI), to attain a 30 cc 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)
See arm/group descriptions.
Other Names:
  • Intraarterial alteplase recombinant tissue plasminogen activator (rTPA)
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:

  1. Dilute 3 vials of 10 mgs (placebo) in 30 cc of sterile water for injection (SWI), to attain a 30 cc 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)
See arm/group descriptions.

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.
The primary outcome will be the proportion of patients with a mRS 0 to 1 at 90 days
Day 90 after treatment.

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.
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).
Day 90 after treatment.
Infarct expansion ratio.
Time Frame: 48 (+/- 24h) hours of stroke
Infarct Expansion Ratio on DWI-MRI (continuous variable), at 48h (+/- 24h) of stroke
48 (+/- 24h) hours of stroke
Rate of infarct expansion at 24 hours.
Time Frame: 48 (+/- 24h) hours of stroke
Proportion of patients with/without infarct expansion (dichotomous variable).
48 (+/- 24h) hours of stroke
Final infarct volume.
Time Frame: 48 (+/- 24h) hours of stroke
Infarction Volume on Diffusion Weighted Imaging (Magnetic Resonance Imaging) at 48h (+/- 24h) of stroke onset
48 (+/- 24h) hours of stroke
Angiographic improvement on the Arterial Occlusive Lesion (AOL) scale
Time Frame: 10 minutes after treatment
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.
10 minutes after treatment
TERTIARY OUTCOME: Barthel Scale at day 90
Time Frame: Day 90 after treatment.
Barthel Scale score of 95 to 100, at day 90
Day 90 after treatment.
TERTIARY OUTCOME: Ischemic worsening within 72 hours os stroke onset
Time Frame: 72 hours of stroke onset
Ischemic worsening (≥ 4 points in the NIHSS score) within 72 hours of stroke onset not attributable to stroke recurrence
72 hours of stroke onset
TERTIARY OUTCOME: Quality of life measured at 90 days
Time Frame: Day 90 after treatment.
Quality of life measured with the EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D-3L) at 90 days
Day 90 after treatment.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients with improved mTICI 2b score
Time Frame: 10 minutes after treatment

Proportion of patients with improved mTICI 2b score

  1. IV Alteplase use on admission (yes versus no)
  2. MT started within 7.3h of symptoms onset versus MT started between 7.4h and 24h.
  3. Admission serum glucose concentration≤100 mg/dL versus >100 mg/dL
  4. Males vs. Females
  5. Baseline angiographic score mTICI2b brain reperfusion versus baseline angiographic score eTICI2c/3 brain reperfusion.
10 minutes after treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 5, 2018

Primary Completion (Actual)

May 31, 2021

Study Completion (Actual)

May 31, 2021

Study Registration Dates

First Submitted

March 12, 2019

First Submitted That Met QC Criteria

March 14, 2019

First Posted (Actual)

March 15, 2019

Study Record Updates

Last Update Posted (Actual)

May 20, 2022

Last Update Submitted That Met QC Criteria

May 16, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Deidentified individual participant data on outcome measures will be published along with the main results of the trial.

IPD Sharing Time Frame

The data will become available after publication of main study results.

IPD Sharing Access Criteria

The IPD will be available from the Sponsor of the trial on reasonable request.

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

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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