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

The study objective is to evaluate the safety and efficacy of Intra arterial (IA) Tenecteplase (TNK) as an adjunctive therapy in acute ischemic stroke (AIS) patients with large vessel occlusions (LVO) in the anterior circulation of Internal Carotid Artery (ICA), Middle Cerebral Arteries (M1 and M2) who achieve a reperfusion grade of Modified Treatment in Cerebral Ischemia Scale (mTICI) 2b or higher post-mechanical thrombectomy using Food and Drug Administration (FDA) approved devices.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke; Acute Disease
• Intervention / Treatment: Drug: tenecteplase

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Syed Fazal Zaidi, MD; Phone Number: (419)- 291-8027; Email: Syed.Zaidi2@utoledo.edu
• Study Contact Backup: Name: Tanya Siddiqui; Phone Number: 4192913498

Study Locations

• United States
  • Ohio
    • Toledo, Ohio, United States, 43606
      • Recruiting
      • ProMedica Toledo Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 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. Alberta Stroke Program Early CT Score (ASPECTS) Score ≥6 on baseline Non-contrast Head CT (NCCT)
4. Post-mechanical thrombectomy with ≤5 device passes and mTICI grade 2b or higher.
5. Ability to obtain signed informed consent prior to randomization from LAR or Subject

Exclusion Criteria:

1. Premorbid modified Rankin scale (mRS) score >1
2. Imaging evidence of hemorrhage or mass effect at baseline
3. Platelet count <100,000
4. Active hemorrhagic diathesis, or known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency
5. Active anticoagulation treatment with novel oral anticoagulant (NOACs) taken within the last 48 hours, or INR >1.7
6. Patients requiring active treatment with dual antiplatelet agents (e.g. proximal cervical carotid artery stenting)
7. Pregnant or lactating
8. Previous known allergy to TNK
9. Major surgery in past 30 days
10. Patient is on or requires dialysis
11. History of intracranial hemorrhage or serious head trauma at any time
12. Any condition in the opinion of the enrolling physician that would preclude the patient from participating
13. Pre-existing medical, neurological, or psychiatric disease that would confound the neurological or functional evaluation
14. Severe, uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) that is refractory to treatment
15. History of acute ischemic stroke in the last 60 days and/or has received previous treatment with a thrombolytic within the last 90 days
16. Presumed septic embolus; suspicion of bacterial endocarditis
17. Suspicion of aortic dissection
18. Intracranial neoplasm
19. Any terminal medical condition with life expectancy less than 6 months
20. Concurrent enrollment in another trial that could confound the results of this study
21. Patient is unlikely to return for 90-day follow-up.
22. Intravenous tissue plasminogen activator (tPA) administered concurrently with Intra-arterial TNK

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Randomized to Intra Arterial (IA) Tenecteplase (TNK); Patients will receive IA- TNK	Drug: tenecteplase; Patients treated with standard of care mechanical thrombectomy (MT) that achieved mTICI 2b or higher revascularization. Patients will be randomized into one of two arms: IA TNK or control.
No Intervention: Randomized to best medical practice; Patients will receive best medical practice treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Efficacy Endpoint- Modified Rankin Scale (mRS)	Proportion of patients with Modified Rankin Scale (mRS) 0-1 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 (+/- 30 days) post treatment.
Primary Safety Endpoint- Incidence of 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) associated with a Parenchymal hematoma, Type 2 (PH2) brain hemorrhage, according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria, within 24 (±12) hours from randomization.	24 hours (+/-12 hours) post treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ordinal Modified Rankin Scale (mRS)	Ordinal mRS at 90 day. 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 (+/-30 days) post treatment.
Functional Independence	Proportion of patients with functional independence, defined as a mRS of 0-2 at 90 days.	90 days (+/- 30 days) post treatment.
Final Revascularization Grade	Final revascularization grade at end of IA treatment among those with less than mTICI 3 prior to IA-TNK administration.	Immediate post treatment.
Mortality rate at 90 days	Mortality rate at 90-days	Mortality rate at 90-days (+/- 30 days) post treatment.
Mortality Rate at discharge	Mortality rate at discharge.	Day 6 (+/-1 day) or Discharge post treatment.
Infarct Volume Post Procedure	Infarct volume on post-procedure follow-up scans performed at 24 ± 12 hours following mechanical thrombectomy.	24 hours (+/- 12 hours) post treatment.
Asymptomatic Intracranial hemorrhage	Incidence of any asymptomatic intracranial hemorrhage	24 hours (+/- 12 hours) post treatment.
Mean Number of Boluses	Mean number of boluses to achieve improvement in reperfusion to mTICI 2c and mTICI 3 among those without mTICI3 prior to IA-TNK administration.	Immediate post procedure.

Collaborators and Investigators

• Sponsor: ProMedica Health System

Publications and helpful links

General Publications

• Zaidi SF, Castonguay AC, Zaidat OO, Jadhav AP, Sheth SA, Haussen DC, Nguyen TN, Burgess RE, Alhajala HS, Gharaibeh K, Salahuddin H, Rao R, Oliver MJ, Jumaa MA. Safety of Adjunctive Intraarterial Tenecteplase Following Mechanical Thrombectomy: The ALLY Pilot Trial. Stroke. 2025 Feb;56(2):355-361. doi: 10.1161/STROKEAHA.124.048846. Epub 2025 Jan 8.

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2025
• Primary Completion (Estimated): May 30, 2028
• Study Completion (Estimated): May 30, 2028

Study Registration Dates

• First Submitted: April 17, 2025
• First Submitted That Met QC Criteria: April 21, 2025
• First Posted (Actual): April 29, 2025

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Stroke; TNK; Thrombolytic
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Ischemic Stroke; Stroke; Acute Disease; Amino Acids, Peptides, and Proteins; Proteins; Hydrolases; Enzymes; Enzymes and Coenzymes; Blood Proteins; Endopeptidases; Peptide Hydrolases; Serine Endopeptidases; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Tissue Plasminogen Activator; Tenecteplase
• Other Study ID Numbers: ALLY II

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