Adjunctive Intra-arterial Tenecteplase Following Mechanical Thrombectomy Pilot Trial (ALLY)

Prospective, single center, non-randomized, pilot study to assess the feasibility of IA TNK following standard of care mechanical thrombectomy (MT) in patients with AIS. Participants will receive IA TNK after achieving mTICI 2b or 2c reperfusion with standard of care MT. Patients enrolled into the study will be followed for 3 months after treatment with IA TNK.

Study Overview

• Status: Completed
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: intra-arterial tenecteplase

Detailed Description

As current MT technology is not amenable to retrieval of distal occlusions (M3/M4, etc), we hypothesize that IA lytic may play an important role as an adjunctive therapy to open up distal vessels (after the primary LVO has been removed) to achieve complete or near complete reperfusion. In this pilot trial, our goal is to assess the feasibility and safety of IA Tenecteplase (TNK) as an adjunctive therapy following standard of care mechanical thrombectomy (MT) in patients with AIS. A total of 20 patients will be enrolled into the ALLY pilot study.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Toledo, Ohio, United States, 43606
      • Promedica Toledo Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Age 18-85
• 2. Anterior circulation ischemic stroke symptoms with confirmed occlusion (ICA, M1, or M2) on angiogram and mechanical thrombectomy initiated within 24 hours since last known well
• 3. a. Patients treated less than 6 hours since last known well with ASPECTS >6. b. Patients treated beyond 6 hours since last known well, CT or MRI perfusion scan showing favorable mismatch profile (Target mismatch profile on CT perfusion or MRI (ischemic core volume is <70ml, mismatch ratio is >1.8 and mismatch volume is >15ml)
• 4. Post-mechanical thrombectomy with ≤5 device passes and mTICI grade 2b or 2c with persistent occlusion(s) in terminal branches not amenable to MT.
• 5. Signed informed consent

Exclusion Criteria:

• 1. Premorbid modified Rankin scale (mRS) score of 4 or greater
• 2. Presence of any hemorrhage and/or ASPECT score ≤6 on baseline head CT
• 3. Platelet count <100,000
• 4. Known bleeding diathesis
• 5. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency
• 6. Active anticoagulation treatment with novel oral anticoagulant (NOACs) taken within the last 48 hours, or INR >1.8
• 7. Patients requiring active treatment with dual antiplatelet agents (e.g. proximal cervical carotid artery stenting)
• 8. Pregnant or lactating
• 9. Previous known allergy to TNK
• 10. Major surgery in past 30 days
• 11. Patient is on or requires dialysis
• 12. History of intracranial hemorrhage or serious head trauma at any time
• 13. Any condition in the opinion of the enrolling physician that would preclude the patient from participating
• 14. Pre-existing medical, neurological, or psychiatric disease that would confound the neurological or functional evaluation
• 15. Severe, uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) that is refractory to treatment
• 16. History of acute ischemic stroke in the last 60 days
• 17. Presumed septic embolus; suspicion of bacterial endocarditis
• 18. Suspicion of aortic dissection
• 19. Intracranial neoplasm
• 20. Any mass effect
• 21. Any terminal medical condition with life expectancy less than 6 months
• 22. Concurrent enrollment in another trial that could confound the results of this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intra-arterial Tenecteplase; Participants will receive intra-arterial Tenecteplase after achieving mTICI 2b or 2c reperfusion with standard of care MT.	Drug: intra-arterial tenecteplase; intra-arterial drug administered after mechanical thrombectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of any intracranial hemorrhage and neurologic worsening	Incidence of any intracranial hemorrhage and neurologic worsening of at least 4 points on the National Institute of Health Stroke Scale (NIHSS), according to the European Cooperative Acute Stroke Study II (ECASS-II) criteria, within 24 hours of treatment with IA TNK	24 hours post-treatment with intra-arterial Tenecteplase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improved reperfusion	Proportion of patients with improved reperfusion (mTICI 2c/3) at end of IA treatment	immediate post-treatment
Improved reperfusion	Proportion of patients with improvement of reperfusion to mTICI 2c, mTICI 3, and mTICI 2c-3.	immediate post-treatment
Ordinal modified Rankin Scale Score	Ordinal modified Rankin Scale Score at 90 days. The mRS is the standard tool to assess neurological outcome in trials with acute severe brain disease. The scale runs from 0-6, running from perfect health without symptoms (= 0) to death (= 6).	90 days post-treatment
Functional Independence	Proportion of patients with functional independence, defined as a mRS of 0-2 at 90 days	90 days post-treatment
Final revascularization grade	Final revascularization grade at end of IA treatment using the modified Thrombolysis in Cerebral Infarction (mTICI) grading scale.	immediate post-treatment
Mortality	Mortality rate at discharge	Hospital Discharge (Day 6 post-randomization (+/- 1 day))
Asymptomatic intracranial hemorrhage	Incidence of any asymptomatic intracranial hemorrhage	24 hours post-treatment
Mean number of boluses	Mean number of boluses to achieve improvement in reperfusion to mTICI 2c and mTICI 3	Immediate post-procedure

Collaborators and Investigators

• Sponsor: ProMedica Health System
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Syed F Zaidi, MD, ProMedica Health System

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2022
• Primary Completion (Actual): September 12, 2023
• Study Completion (Actual): November 1, 2023

Study Registration Dates

• First Submitted: November 16, 2021
• First Submitted That Met QC Criteria: December 28, 2021
• First Posted (Actual): December 29, 2021

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: stroke; thrombolytic; distal emboli
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tenecteplase
• Other Study ID Numbers: ALLY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No