Inhaled Nitric Oxide in Acute Ischemic Stroke Patients Undergoing Mechanical Thrombectomy (iNO)

April 22, 2026 updated by: Wake Forest University Health Sciences

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

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This dose escalation phase I study is to evaluate the safety and feasibility of iNO as adjunctive therapy in the treatment of AIS in adult patients with clinically significant strokes.

iNO will act as a selective vasodilator to ischemic tissues in the brain, increasing perfusion to the area of the brain most at risk (penumbra) in AIS patients. This therapy will help to increase collateral circulation and perfusion to the penumbra, salvaging this tissue and limiting the volume of core infarct while mitigating reperfusion injury to the salvaged tissue.

Protection of ischemic penumbra is paramount in IAMT stroke patients. IAMT to re-establish blood flow during AIS from a large vessel occlusion (LVO) reduces death and disability. Initially this intervention was recommended up until 6 hours after symptom onset, but more recently has proven safe and effective up to 16 and 24 hours after stroke onset in select patients. These studies have confirmed the long believed thought that supporting ischemic penumbra during AIS helps limit the size of the ultimate core infarct and therefore reduces disability and death from stroke. Treatment aimed at protecting ischemic penumbra is thus paramount to treatment and research endeavors in AIS patients.

iNO protects ischemic penumbra. Nitric oxide is an endothelial-derived vasodilator and has been shown to mediate cytoprotection after ischemic reperfusion injury and appears to aid in ischemic preconditioning signaling pathways. iNO has been shown to cause selective dilation of arterioles in the ischemic penumbra of stroke and subarachnoid hemorrhage animal models, helping augment the cerebral microcirculation and improve penumbral blood flow. This has been shown to reduce ischemic brain damage, limit core infarct, and consistently improve neurological outcome in a middle cerebral artery AIS mouse model

Study Type

Interventional

Enrollment (Estimated)

36

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Recruiting
        • Carolinas Medical Center
        • Principal Investigator:
          • William Stetler, MD
      • Charlotte, North Carolina, United States, 28204
        • Recruiting
        • Atrium Health
        • Principal Investigator:
          • William Stetler, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 or dominant proximal M2 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose 2 Group
Dose 2- Inhaled Nitrous Oxide (iNO) 40ppm.
Drug: iNO
Inhaled Nitrous Oxide
Other Names:
  • Inhaled Nitrous Oxide
Experimental: Dose 3 Group
Dose 3- Inhaled Nitrous Oxide (iNO) 50ppm.
Drug: iNO
Inhaled Nitrous Oxide
Other Names:
  • Inhaled Nitrous Oxide
Experimental: Dose 4 Group
Dose 4- Inhaled Nitrous Oxide (iNO) 60ppm.
Drug: iNO
Inhaled Nitrous Oxide
Other Names:
  • Inhaled Nitrous Oxide
Experimental: Dose 5 Group
Dose 5- Inhaled Nitrous Oxide (iNO) 70ppm.
Drug: iNO
Inhaled Nitrous Oxide
Other Names:
  • Inhaled Nitrous Oxide
Experimental: Dose 6 Group
Dose 6- Inhaled Nitrous Oxide (iNO) 80ppm.
Drug: iNO
Inhaled Nitrous Oxide
Other Names:
  • Inhaled Nitrous Oxide
Experimental: Dose 1 Group
Dose 1- Inhaled Nitrous Oxide (iNO) 20ppm.
Drug: iNO
Inhaled Nitrous Oxide
Other Names:
  • Inhaled Nitrous Oxide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum safe dose of iNO for AIS patients - assessing for reperfusion hemorrhage/symptomatic intracranial hemorrhage (sICH)
Time Frame: Year 2
To establish a maximum safe dose of iNO for acute ischemic (non-bleeding) stroke (AIS) patients, assessing for reperfusion hemorrhage/symptomatic intracranial hemorrhage (sICH)
Year 2

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in pre-endovascular mechanical thrombectomy (IAMT) and post-IAMT core infarct volume
Time Frame: Year 2
Core infarct measurement pre/post
Year 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wake Forest University Health Sciences

Collaborators

Mallinckrodt

Investigators

  • Principal Investigator: William R Stetler, MD, Wake Forest University Health Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 16, 2026

Primary Completion (Estimated)

August 1, 2028

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

May 12, 2023

First Submitted That Met QC Criteria

May 12, 2023

First Posted (Actual)

May 23, 2023

Study Record Updates

Last Update Posted (Actual)

April 23, 2026

Last Update Submitted That Met QC Criteria

April 22, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00090271

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Cerebrovascular Disorders

Clinical Trials on iNO

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Ireland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe