Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05032781 |
| Other study ID # |
20-1198 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2021 |
| Est. completion date |
June 2024 |
Study information
| Verified date |
March 2024 |
| Source |
Northwell Health |
| Contact |
Thomas W Link, MD, MS |
| Phone |
516-562-4300 |
| Email |
tlink[@]northwell.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Ischemic stroke is the leading cause of long-term disability in the United States.
Endovascular intervention with mechanical thrombectomy has become the standard of care for
acute large vessel occlusion (LVO) stroke since multiple clinical trials demonstrated
improved long-term clinical outcomes with treatment. However, despite high rates of
successful vessel recanalization and thus reperfusion of ischemic brain tissue in current
practice, many patients continue to suffer debilitating strokes and poor long-term functional
outcome. Pharmacologic neuroprotection could potentially present a means of addressing this
mismatch in radiologic vs. clinical outcomes by protecting and salvaging damaged brain
tissue. Intra-arterial delivery of a cocktail of neuroprotective therapy at the time of
endovascular reperfusion would provide immediate, targeted therapy directly to the damaged
brain territory. Hypothermia, minocycline and magnesium can target multiple facets of the
complex ischemic injury cascade, and have each demonstrated neuroprotection in multiple
preclinical models. This is a phase I trial that aims to demonstrate safety and feasibility
of administering cold saline, minocycline, and magnesium sulfate intra-arterially immediately
after thrombectomy in stroke interventions.
Description:
This is a phase I, single center, single arm clinical trial with dose escalation design.
Location: North Shore University Hospital in Manhasset, NY
Study population: Subjects aged 18-90 years undergoing mechanical thrombectomy for acute
ischemic stroke due to large vessel occlusion at North Shore University Hospital
Primary Objective: To demonstrate the safety and feasibility of intra-arterial administration
of a cocktail of neuroprotective agents at the time of reperfusion in endovascular stroke
intervention for acute ischemic stroke due to large vessel occlusion.
Secondary Objectives:
A) To describe the feasibility of delivering a combination of neuroprotective agents directly
into the affected internal carotid artery immediately after recanalization of an occluded
vessel in ischemic stroke intervention.
B) To describe the maximum tolerated dose of a combination of 4C saline at 30 ml/min for 10
minutes, minocycline, and magnesium sulfate directly into the affected internal carotid
artery immediately after recanalization of an occluded vessel in ischemic stroke
intervention.
C) To describe the clinical outcomes of the patients undergoing the experimental procedure
and compare to historical controls.
Primary Endpoint: Presence of symptomatic intracranial hemorrhage within 24 hours of
treatment; presence of serious adverse event related to the administration of intra-arterial
cold saline, minocycline or MgSO4; and technical feasibility of the proposed experimental
treatment.
Secondary Endpoints: Total volume of infarct on MRI 24 hours after procedure, clinical
outcome as measured by the NIHSS prior to discharge and MRS at 90 day follow up.
Study design:
Based on the available literature, the target dose of Minocycline and MgSO4 is 6 mg/kg and
2g, respectively. For targeted hypothermia, 4C normal saline will be infused at a rate of 30
ml/min to achieve an estimated drop in temperature in the ipsilateral hemisphere to 33-34C
within 10 minutes.
To ensure adequate safety measures, a dose escalation design is employed to carefully
evaluate for adverse events throughout the study. The standard "3+3" dose escalation design
will be used in the 3 groups described below. Within each group, at each dosage, if none of
the first 3 patients experience a related adverse event, the study proceeds to the next group
or dose level. If one of the 3 patients experiences an adverse event, then an additional 3
patients will be treated at that dose level before proceeding. Escalation will continue only
if a maximum of 1 out of 6 patients experience an adverse event. If 2 or more patients at a
given dose level experience an adverse event, then the maximum tolerated dose (MTD) will be
determined as the preceding dose level.
Group 1: IA cold saline alone 3-6 patients receive 4C at 30 ml/min over 10 min
Group 2: IA cold saline + Minocycline 3-6 patients receive IA cold saline + 2 mg/kg
Minocycline; 3-6 patients receive IA cold saline + 4 mg/kg Minocycline; 3-6 patients receive
IA cold saline + 6 mg/kg Minocycline
Group 3: IA cold saline + Minocycline + Magnesium sulfate 3-6 patients receive IA cold saline
+ MTD Minocycline + 2g MgSO4; 3-6 patients receive IA cold saline + MTD Minocycline + 4g
MgSO4
Both the Minocycline and MgSO4 will be reconstituted within the 300 ml of cold saline to be
administered together.
Follow up:
Post-stroke intervention care will proceed as standard of care with the addition of screening
for adverse events related to the IA administration of cold saline, minocycline and/or
magnesium sulfate.
Day 1: CT or MRI within 24h of intervention, neurologic exam, routine labs, NIHSS.
Day of discharge: neurologic exam, routine labs, NIHSS, mRS. Day 90: neurologic exam, NIHSS,
mRS.
