Inhaled Nitric Oxide in Acute Ischemic Stroke Patients Undergoing Mechanical Thrombectomy: A Phase I Drug Pilot Research Plan

IRB00090271

The purpose of this study is to determine the safety and feasibility of using inhaled nitric oxide (iNO) in patients undergoing intra-arterial mechanical thrombectomy (blood clot extraction or IAMT) for treatment of acute ischemic (non-bleeding) stroke (AIS).

2024-06-01

2025-02-01

2025-07-01

Not yet recruiting

Early phase I

27

Inclusion Criteria: * Age 18 and \< 80 * Clinical evidence of acute ischemic (non-bleeding) stroke (AIS) with NIH Stroke Scale of 6 or higher * Non-contrast Computed tomography (CT) Head with ASPECT (Alberta Stroke Program Early CT) score 6 * Symptom onset began \< 16 hours from initiation of intra-arterial mechanical thrombectomy (IAMT) procedure * CT Angiogram (CTA) evidence of anterior circulation MCA (Middle Cerebral Artery) M1 segment occlusion. * CT Perfusion (CTP) evidence of core infarct volume of \< 70ml and a ratio of ischemic tissue to initial core infarct volume of 1.8 or greater, and an absolute volume of penumbra of 15ml or greater * Patient or patient's representative provides consent * Pre-stroke modified Rankin Scale (mRS) of \< =2 * General endotracheal anesthesia (GETA) is planned to be used, as standard care, for IAMT * Treatment with iNO requires mechanical ventilation. Because IAMT can be performed using conscious sedation and not GETA, only those patients for which the procedure is planned with GETA will be included. The decision for the type of anesthetic depends on the severity of stroke, region of brain affected by the stroke, and the ability for the patient to cooperate for the procedure. Exclusion Criteria: * Hypotension at presentation, defined as systolic blood pressure (SBP) \< 100 or MAP \< 60; profound hypertension with SBP \>185 or DBP \>110mmHg unable to be controlled with IV medications * Inability to undergo a brain MRI (e.g., implanted pacemaker) * Patients who received IV tPA \>4.5hrs after symptom onset * Coaguloapathy, defined as platelet count \< 50,000, INR \>3.0, PTT \> 3x normal, use of novel anticoagulants with eGFR \< 30ml/min * Vulnerable Subjects including: mentally ill or incompetent patients, those with diminished decision-making capacity, prisoners, inpatient care for long-term chronic illness, terminally ill, pregnant women, and children * Any form of hemorrhage on non-contrast CT Head or mass lesion * Severe head injury within 90 days * Pre-existing severe neurological/psychiatric disease * Seizure at stroke onset (unable to assess NIHSS) * Blood glucose \< 50mg/dL or \>400mg/dL * Hemoglobin \<7mmol/L * eGFR \< 30ml/min * Allergy to contrast media * Presumed septic embolus as source of stroke * Flow limiting intracranial or extracranial carotid stenosis, or complete carotid occlusion

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'The study has been designed to follow a standard 3+3 cohort expansion design, assessing 5 doses. Specifically, 3 individuals will begin at dose 1. If none of these individuals experience a dose limiting toxicity (DLT), then the dose will be escalated to dose 2. DLT is defined as a patient experiencing sICH, our primary outcome measure, or any other listed ASE. Dose escalation will continue after each set of 3 individuals until at least one person experiences DLT. If only 1 of the 3 experience a DLT, the cohort will be expanded to 6 (an additional 3). If 2 of the 6 experience DLTs, then dose escalation is stopped and the previous dose level (one level below) is declared the maximum tolerated dose. If 2 of the initial 3 experience DLT, the previous dose level (one level below) is declared the maximum tolerated dose. However, if only 1 of 6 experience DLT, the dose will escalate.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 27, 'type': 'ESTIMATED'}}

2024-04-12