Inhaled Nitric Oxide for Ischemic Stroke

(iNO Trial)

Recruiting at 1 trial location

Overseen By Anna M Helms, RN

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

27 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

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.

What data supports the effectiveness of the treatment inhaled nitric oxide (iNO) for ischemic stroke?

Research shows that inhaled nitric oxide (iNO) can improve blood flow and reduce brain damage in animal models of stroke and other brain injuries. It has been effective in reducing brain injury in mice and improving outcomes after cardiac arrest in rats, suggesting potential benefits for ischemic stroke. ^{1 2 3 4 5}

Is inhaled nitric oxide (iNO) generally safe for humans?

Inhaled nitric oxide (iNO) has been used safely in various medical situations, including in premature infants and critically ill patients during transport. Some potential side effects include low blood pressure and methemoglobinemia (a condition where hemoglobin can't release oxygen effectively), but these are monitored and managed in clinical settings. ^{6 7 8 9 10}

How is the treatment inhaled nitric oxide (iNO) different from other treatments for ischemic stroke?

Inhaled nitric oxide (iNO) is unique because it is administered through inhalation and works by dilating blood vessels, which can improve blood flow to the brain and reduce inflammation after a stroke. This approach is different from standard treatments that often focus on dissolving blood clots or preventing new ones from forming. ^{2 3 4 10 11}

Research Team

William R Stetler, MD

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Dose 5 Group Experimental Treatment 1 Intervention

Dose 5- Inhaled Nitrous Oxide (iNO) 80ppm.

Group II: Dose 4 Group Experimental Treatment 1 Intervention

Dose 4- Inhaled Nitrous Oxide (iNO) 70ppm.

Group III: Dose 3 Group Experimental Treatment 1 Intervention

Dose 3- Inhaled Nitrous Oxide (iNO) 60ppm.

Group IV: Dose 2 Group Experimental Treatment 1 Intervention

Dose 2- Inhaled Nitrous Oxide (iNO) 50ppm.

Group V: Dose 1 Group Experimental Treatment 1 Intervention

Dose 1- Inhaled Nitrous Oxide (iNO) 40ppm.

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

Findings from Research

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) 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]

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) 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]

References

1. England 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. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Neuroprotection by inhaled nitric oxide in a murine stroke model is concentration and duration dependent. [2013]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Inhaled Nitric Oxide Treatment for Aneurysmal SAH Patients With Delayed Cerebral Ischemia. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Inhaled Nitric Oxide Use and Outcomes in Critically Ill Children With a History of Prematurity. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Inhaled nitric oxide protects males but not females from neonatal mouse hypoxia-ischemia brain injury. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

The safety and efficacy of nitric oxide therapy in premature infants. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

Safety of Nurse-Managed Inhaled Nitric Oxide During Critical Care Interfacility Transport. [2023]

8. England 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Utility of routine methemoglobin laboratory assays in critically ill pediatric subjects receiving inhaled nitric oxide. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

The influence of inhaled nitric oxide on cerebral blood flow and metabolism in a child with traumatic brain injury. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Inhaled Nitric Oxide as an Adjunct to Thrombolytic Therapy in a Patient with Submassive Pulmonary Embolism and Severe Hypoxemia. [2022]