Cerebrovascular DisordersPhase 1iNONCT05871606
Inhaled Nitric Oxide in Acute Ischemic Stroke Patients Undergoing Mechanical Thrombectomy
A Phase 1 study testing iNO in people with Cerebrovascular Disorders and Acute Cerebrovascular Disease, run by Wake Forest University Health Sciences at 2 sites in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cerebrovascular Disorders, Acute Cerebrovascular Disease
- What is being tested?
- iNO
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 2 sitesUnited States
- Study dates
- 16 Apr 2026to 1 Dec 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Carolinas Medical Center
Charlotte, North Carolina, 28203
William Stetler, MD
- Recruiting
Atrium Health
Charlotte, North Carolina, 28204
William Stetler, MD
About this study
Official title: 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).
Read the 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
- Being tested
- iNO
- Keywords
- Stroke, blood clot extraction, large vessel occlusion
- Medical subject headings
- Cerebrovascular Disorders, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
iNODrug
Also called Inhaled Nitrous Oxide
Inhaled Nitrous Oxide
| Study group | Role | What they receive |
|---|---|---|
| Dose 2 Group | Experimental | Dose 2- Inhaled Nitrous Oxide (iNO) 40ppm. Receives: Drug: iNO |
| Dose 3 Group | Experimental | Dose 3- Inhaled Nitrous Oxide (iNO) 50ppm. Receives: Drug: iNO |
| Dose 4 Group | Experimental | Dose 4- Inhaled Nitrous Oxide (iNO) 60ppm. Receives: Drug: iNO |
| Dose 5 Group | Experimental | Dose 5- Inhaled Nitrous Oxide (iNO) 70ppm. Receives: Drug: iNO |
| Dose 6 Group | Experimental | Dose 6- Inhaled Nitrous Oxide (iNO) 80ppm. Receives: Drug: iNO |
| Dose 1 Group | Experimental | Dose 1- Inhaled Nitrous Oxide (iNO) 20ppm. Receives: Drug: iNO |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum safe dose of iNO for AIS patients - assessing for reperfusion hemorrhage/symptomatic intracranial hemorrhage (sICH)
To establish a maximum safe dose of iNO for acute ischemic (non-bleeding) stroke (AIS) patients, assessing for reperfusion hemorrhage/symptomatic intracranial hemorrhage (sICH)
Measured: Year 2
Secondary outcomes (1)
Change in pre-endovascular mechanical thrombectomy (IAMT) and post-IAMT core infarct volume
Core infarct measurement pre/post
Measured: Year 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2023
- Study start16 Apr 2026
- Primary completion1 Aug 2028 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebrovascular DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- William R Stetler, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05871606
- Sponsor's protocol ID
- IRB00090271
- Acronym
- iNO
- Status last verified
- Apr 2026
- First submitted
- 12 May 2023
- Last updated
- 23 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhaled Nitric Oxide in Acute Ischemic Stroke Patients Undergoing Mechanical Thrombectomy: A Phase I Drug Pilot Research Plan
- ClinicalTrials.gov ID
- NCT05871606
- Acronym / sponsor ID
- iNO / IRB00090271
- Keywords
- Stroke, blood clot extraction, large vessel occlusion
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Study start
- 16 Apr 2026 (actual)
- Primary completion
- 1 Aug 2028 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 23 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Dose 2 Group | Experimental | Drug: iNODose 2- Inhaled Nitrous Oxide (iNO) 40ppm. |
| Dose 3 Group | Experimental | Drug: iNODose 3- Inhaled Nitrous Oxide (iNO) 50ppm. |
| Dose 4 Group | Experimental | Drug: iNODose 4- Inhaled Nitrous Oxide (iNO) 60ppm. |
| Dose 5 Group | Experimental | Drug: iNODose 5- Inhaled Nitrous Oxide (iNO) 70ppm. |
| Dose 6 Group | Experimental | Drug: iNODose 6- Inhaled Nitrous Oxide (iNO) 80ppm. |
| Dose 1 Group | Experimental | Drug: iNODose 1- Inhaled Nitrous Oxide (iNO) 20ppm. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| iNOAlso: Inhaled Nitrous OxideInhaled Nitrous Oxide | Drug | Dose 1 Group, Dose 2 Group, Dose 3 Group, Dose 4 Group, Dose 5 Group, Dose 6 Group |
Primary outcome
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)
1 secondary outcome
Change in pre-endovascular mechanical thrombectomy (IAMT) and post-IAMT core infarct volume
Time frame: Year 2
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
William R Stetler, MD principal investigator
Wake Forest University Health Sciences
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing iNO in people with Cerebrovascular Disorders and Acute Cerebrovascular Disease, run by Wake Forest University Health Sciences at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anna M Helms, MSN, RN (704-446-0473, anna.m.helms@advocatehealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum safe dose of iNO for AIS patients - assessing for reperfusion hemorrhage/symptomatic intracranial hemorrhage (sICH) (time frame: Year 2). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2026.