Intraarterial Alteplase Versus Placebo After Mechanical Thrombectomy

NCT03876119 | Completed Phase 2 DMC

• 1 other identifier: CHOICE
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Stroke, Acute

Keywords

Mechanical Thrombectomy; Recanalization; Reperfusion

Outcome Measures

Primary Outcomes (1)

• Good outcome at 90 days

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

  Day 90 after treatment.

Secondary Outcomes (8)

• Shift analysis of the 90-day modified Rankin Scale (mRS).

  Day 90 after treatment.

• Infarct expansion ratio.

  48 (+/- 24h) hours of stroke

• Rate of infarct expansion at 24 hours.

  48 (+/- 24h) hours of stroke

• Final infarct volume.

  48 (+/- 24h) hours of stroke

• Angiographic improvement on the Arterial Occlusive Lesion (AOL) scale

  10 minutes after treatment

Other Outcomes (1)

• Proportion of patients with improved mTICI 2b score

  10 minutes after treatment

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. 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)

Drug: Intraarterial alteplase

Placebo

PLACEBO COMPARATOR

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)

Drug: Placebo

Interventions

Intraarterial alteplase DRUG

See arm/group descriptions.

Also known as: Intraarterial alteplase recombinant tissue plasminogen activator (rTPA)

Intraarterial alteplase

Placebo DRUG

See arm/group descriptions.

Placebo

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, 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

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
• 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

Sponsors & Collaborators

• Hospital Clinic of Barcelona: lead
• Fundació La Marató de TV3: collaborator
• Fundacion Clinic per a la Recerca Biomédica: collaborator

Study Sites (7)

Germans Trias i Pujol Hospital

Badalona, Spain

Location

Hospital Clinic of Barcelona

Barcelona, 08036, Spain

Location

Hospital del Mar

Barcelona, 08036, Spain

Location

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Universitari de Bellvitge

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebrón

Barcelona, Spain

Location

Hospital Josep Trueta (HJT)

Girona, 17007, Spain

Location

Related Publications (5)

• 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 RESULT

MeSH Terms

Conditions

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

• 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

  University Hospital of Girona Dr. Josep Trueta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The solutions of alteplase or placebo are limpid, transparent and colorless. Alteplase (Actilyse 10 mg powder and solvent for solution for injection and infusion) and placebo will be provided in kind by Boëhringer Ingelheim. The secondary conditioning of the investigation treatment will be performed by Alcura Health Spain S.A.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Comprehensive Stroke Center, Hospital Clinic Barcelona. Professor of Neurology, University of Barcelona.

Model Details: 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.

Study Record Dates

• First Submitted: March 12, 2019
• First Posted: March 15, 2019
• Study Start: December 5, 2018
• Primary Completion: May 31, 2021
• Study Completion: May 31, 2021
• Last Updated: May 20, 2022

Record last verified: 2022-05

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 (7)