Ischemic Stroke
Conditions
Keywords
thrombolytic, stroke, distal emboli
Brief summary
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.
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.
Interventions
intra-arterial drug administered after mechanical thrombectomy
Sponsors
ProMedica Health System
Genentech, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will receive intra-arterial Tenecteplase after achieving mTICI 2b or 2c reperfusion with standard of care mechanical thrombectomy.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Any Intracranial Hemorrhage and Neurologic Worsening | 24 hours (+/- 8 hours) post-treatment with intra-arterial Tenecteplase | Number of participants with any incidence of 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 (+/- 8 hours) of treatment with IA TNK. This measure was assessed by imaging (NCCT/MRI) done within this time frame for all the enrolled study participants. This is the primary study-specific baseline measure for the ALLY study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ordinal Modified Rankin Scale Score | 90 days (+/- 30 days) post-treatment | Ordinal modified Rankin Scale Score at 90 days (+/- 30 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). This assessment was assessed by the study site personnel. The mRS score could have been obtained over the phone via a structured questionnaire if all attempts to perform as in-person assessment had failed. |
| Final Revascularization Grade | immediate post-treatment | Final revascularization grade at end of IA treatment using the modified Thrombolysis in Cerebral Infarction (mTICI) scale. mTICI of grade 3: complete anterograde perfusion with normal filling of all distal branches. mTICI 2c is: Near complete anterograde perfusion to the tissue distal to the baseline occlusion but \< 100% (slow flow in a few distal cortical vessels or presence of small distal cortical emboli). mTICI 2b is: Anterograde Perfusion to the tissue distal to the baseline occlusion but ≥ 50% of the target ischemic territory. The first bolus of intra-arterial TNK was given as soon as possible after mechanical thrombectomy. A dose of 1.5 mL (1 mg/mL) was infused over 1 minute. After 5 minutes, reperfusion was assessed. If TICI 3 was not achieved, a second 1.5 mg bolus was given, followed by another 5-minute assessment. If needed, a third 1.5 mg bolus was given in the same way. After the final 5-minute wait, the final mTICI score was recorded. |
| Incidence of Any Asymptomatic Intracranial Hemorrhage | 24-Hour (+/- 8 hours) post-treatment | Number of participants with any incidence of asymptomatic intracranial hemorrhage. This was assessed by the imaging done at 24 hours from the time of treatment. Both NCCT or MRI were acceptable but MRI was preferred. |
| Number of Boluses | Immediate post-procedure | Number of boluses given to achieve improvement in reperfusion to mTICI 2c and mTICI 3. This was assessed post-procedure immediately. The first bolus of intra-arterial (IA) tenecteplase (TNK) was given as soon as possible after the mechanical thrombectomy (MT) procedure was complete. A dose of 1.5 mL IA TNK (1 mg/mL) will be infused over 1 minute. After the infusion was complete, the investigator waited 5 minutes before checking the reperfusion status. If complete reperfusion (TICI 3) was not achieved, a second 1.5 mg bolus was given over 1 minute, followed again by a 5-minute waiting period before reassessment. If TICI 3 reperfusion was still not achieved, a third 1.5 mg bolus was administered over 1 minute. After this infusion, the investigator waited another 5 minutes and then assessed the reperfusion status. The final modified TICI (mTICI) score will be recorded after the last assessment. |
| Mortality Rate at Discharge | Hospital Discharge (+/-1 day) | This secondary outcome was determined when the participant was discharged, or it was determined on day 6(+/- 1 day). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSyed F Zaidi, MD
ProMedica Health System
Participant flow
Recruitment details
20 MT AIS patients enrolled and treated with IA TNK.
Pre-assignment details
218 MT AI patients assessed for eligibility. Excluded 95 patients with mTICI 3 and 16 patients with mTICI 0, 1, 2a. Excluded 87 patients on demographic and/or other inclusion/exclusion criteria.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 66.1 Years STANDARD_DEVIATION 0.4 |
| Region of Enrollment United States | 20 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 20 |
| other Total, other adverse events | 12 / 20 |
| serious Total, serious adverse events | 9 / 20 |
Outcome results
None listed