Inhaled Nitric Oxide for Ischemic Stroke

(iNO Trial)

Recruiting at 1 trial location

Overseen By Anna M Helms, MSN, RN, CCRN, SCRN, NVRN-BC

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Wake Forest University Health Sciences

Must not be taking: Novel anticoagulants

Disqualifiers: Hypotension, Hemorrhage, Severe head injury, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 hours post-stroke onset

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and feasibility of using inhaled nitric oxide (iNO) for individuals undergoing blood clot removal from the brain during an acute ischemic stroke (a stroke where blood flow to the brain is blocked without bleeding). The study will test various doses of iNO to evaluate their effectiveness during the procedure. Candidates may qualify if they have recently experienced a stroke that blocks a major brain artery and are undergoing clot removal with standard anesthesia. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on certain blood thinners or have specific medical conditions, you might need to discuss this with the trial team.

Is there any evidence suggesting that inhaled nitric oxide is likely to be safe for humans?

Research has shown that inhaled nitric oxide (iNO) is generally safe for medical use. It is already approved for some conditions, indicating a strong safety record. Studies have found that inhaled nitric oxide can improve blood flow to the brain during a stroke without causing serious side effects.

When tested at different concentrations, such as 40 parts per million (ppm) and 60 ppm, iNO has been well-tolerated. However, some studies suggest that higher concentrations, like 80 ppm, might be less effective, although no serious side effects have been noted at these levels.

Overall, the past use of iNO in various medical situations supports its safety, making it a promising option for new trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about inhaled nitric oxide (iNO) for ischemic stroke because it offers a new delivery method that targets the condition directly through the respiratory system. Unlike traditional treatments like clot-busting drugs or thrombectomy procedures, iNO is administered via inhalation, potentially offering a quicker and less invasive option. This method leverages nitric oxide's ability to dilate blood vessels, potentially improving blood flow to the brain more rapidly. Additionally, the trial explores various doses, from 40ppm to 80ppm, to optimize effectiveness and safety, which could personalize treatment for different patients.

What evidence suggests that inhaled nitric oxide could be an effective treatment for ischemic stroke?

Research has shown that inhaled nitric oxide (iNO) might help treat strokes caused by blocked blood flow to the brain. Studies have found that iNO can reduce brain swelling, which often occurs after a stroke, and increase blood flow to the brain, protecting nerve cells from damage. Previous studies demonstrated that iNO reduces the size of the brain area affected by the stroke and improves brain function and overall recovery. Early results suggest that by boosting blood flow and reducing swelling, iNO could be a promising new treatment for stroke patients. This trial will evaluate different dosages of iNO to determine the most effective dose for improving outcomes in stroke patients. ^{1 2 3 4 6}

Who Is on the Research Team?

William R Stetler, MD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for adults aged 18-79 who've had a recent ischemic stroke and are undergoing mechanical thrombectomy. They should have had mild to moderate disability before the stroke, show significant symptoms, and be within 16 hours of symptom onset. Patients with severe kidney issues, allergies to contrast media, extreme blood sugar levels or certain other health conditions are excluded.

Inclusion Criteria

I have had a stroke that wasn't caused by bleeding and my condition is serious.

You have had a CT scan of your head without contrast, and the ASPECT score is 6 or lower.

My stroke symptoms started less than 16 hours before my clot removal procedure.

Exclusion Criteria

Inability to undergo a brain MRI (e.g., implanted pacemaker)

I am not in a vulnerable group such as being mentally ill, a prisoner, terminally ill, pregnant, or a child.

I have a blockage in my brain or neck arteries.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inhaled nitric oxide (iNO) at varying doses as adjunctive therapy during mechanical thrombectomy for acute ischemic stroke

Up to 24 hours post-stroke onset

Follow-up

Participants are monitored for safety and effectiveness, including assessment of core infarct volume and maximum safe dose of iNO

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• iNO

Trial Overview The study tests the safety and effectiveness of inhaled nitric oxide (iNO) in patients having a procedure called intra-arterial mechanical thrombectomy to remove blood clots caused by an acute ischemic stroke. Participants must require general anesthesia during this procedure.

How Is the Trial Designed?

Group I: Dose 6 Group Experimental Treatment 1 Intervention

Dose 6- Inhaled Nitrous Oxide (iNO) 80ppm.

Group II: Dose 5 Group Experimental Treatment 1 Intervention

Dose 5- Inhaled Nitrous Oxide (iNO) 70ppm.

Group III: Dose 4 Group Experimental Treatment 1 Intervention

Dose 4- Inhaled Nitrous Oxide (iNO) 60ppm.

Group IV: Dose 3 Group Experimental Treatment 1 Intervention

Dose 3- Inhaled Nitrous Oxide (iNO) 50ppm.

Group V: Dose 2 Group Experimental Treatment 1 Intervention

Dose 2- Inhaled Nitrous Oxide (iNO) 40ppm.

Group VI: Dose 1 Group Experimental Treatment 1 Intervention

Dose 1- Inhaled Nitrous Oxide (iNO) 20ppm.

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Mallinckrodt

Industry Sponsor

Trials

202

Recruited

15,700+

Mario Saltarelli

Mallinckrodt

Chief Medical Officer

MD

Siggi Olafsson

Mallinckrodt

Chief Executive Officer

PhD in Pharmacy

Published Research Related to This Trial

Inhaled nitric oxide (iNO) can be safely managed by trained nurses during the transport of critically ill patients, as demonstrated by a study involving patients transported from March 2020 to August 2022.

Out of the patients studied, only 16.7% experienced hypotension, which was manageable and resolved with medication adjustments, while no serious adverse events like worsening hypoxemia or cardiac arrest were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Nurse-Managed Inhaled Nitric Oxide During Critical Care Interfacility Transport. Troncoso, R., Garfinkel, EM., Kaul, K., et al.[2023]

Inhaled nitric oxide (iNO) at 20 ppm during CPR significantly improved return of spontaneous circulation (ROSC) rates and increased mean arterial pressure in a rat model of cardiac arrest, suggesting enhanced resuscitation outcomes.

The use of 20 ppm iNO also led to better neurological recovery and increased 7-day survival rates compared to control, indicating its potential as a beneficial intervention following cardiac arrest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief inhalation of nitric oxide increases resuscitation success and improves 7-day-survival after cardiac arrest in rats: a randomized controlled animal study. Brücken, A., Derwall, M., Bleilevens, C., et al.[2018]

Inhaled nitric oxide (iNO) therapy significantly increases the risk of renal dysfunction in patients with acute respiratory distress syndrome (ARDS), with an adjusted hazard ratio of 1.59 after accounting for confounding factors.

Older patients (aged 65 and above) are particularly vulnerable to kidney injury associated with iNO therapy, highlighting the need for careful monitoring in this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled nitric oxide and the risk of renal dysfunction in patients with acute respiratory distress syndrome: a propensity-matched cohort study. Ruan, SY., Wu, HY., Lin, HH., et al.[2022]

Inhaled nitric oxide (INO) was used in a study of 163 children in the pediatric ICU, showing that early preterm infants (born <32 weeks) had better outcomes, including more ventilator-free days and lower mortality rates compared to late preterm and full-term infants.

The study suggests that INO was initiated for less severe lung disease in early preterm infants, indicating a need for future clinical trials to standardize criteria for starting INO therapy and to consider the history of prematurity when evaluating its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled Nitric Oxide Use and Outcomes in Critically Ill Children With a History of Prematurity. Maddux, AB., Mourani, PM., Banks, R., et al.[2023]

In a study of 860 premature infants under 32 weeks, low-dose inhaled nitric oxide (iNO) did not significantly improve intact survival at 28 days compared to placebo, with survival rates of 61.4% for iNO and 61.1% for controls.

The use of iNO was found to be safe, showing no significant differences in major complications like intraventricular hemorrhage, necrotizing enterocolitis, or patent ductus arteriosus compared to controls, suggesting it does not increase the risk of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of nitric oxide therapy in premature infants. Hascoet, JM., Fresson, J., Claris, O., et al.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10725028/

Inhaled nitric oxide suppresses neuroinflammation in ... In the current study, we investigated whether alleviating vascular dysfunction by restoring vascular nitric oxide (NO) reduces post-stroke inflammation.

2. ahajournals.org ahajournals.org/doi/10.1161/circresaha.111.253419

Inhalation of Nitric Oxide Prevents Ischemic Brain Damage ... Inhaled nitric oxide thus may provide a completely novel strategy to improve penumbral blood flow and neuronal survival in stroke or other ischemic conditions.

3. jneuroinflammation.biomedcentral.com jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-023-02988-3

Inhaled nitric oxide suppresses neuroinflammation in ... In any case, inhaled NO significantly reduces brain and plasma cytokine levels following ischemic stroke and may thereby prevent further brain ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3390820/

Nitric oxide: considerations for the treatment of ischemic stroke After experimental ischemic stroke, iNO reduced lesion size, improved CBF, cerebral metabolism, and neurological outcome, in part dependent upon improved ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05871606?term=AREA%5BConditionSearch%5D(%22Cerebrovascular%20Disease%22)%20AND%20AREA%5BInterventionSearch%5D(%22Anesthetics%22)&rank=1

Inhaled Nitric Oxide in Acute Ischemic Stroke Patients ... A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006899313002667

Neuroprotection by inhaled nitric oxide in a murine stroke ... At 80 ppm, reduction in infarct volume was not observed at any duration. Additional experiments showed that 60ppm iNO could be transported from lung to brain ...