Neuromonitoring for Hypoxic-Ischemic Brain Injury

(DIFFUSION Trial)

Overseen By Rebecca Grey

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of British Columbia

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Coagulopathy, Severe TBI, Stroke, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to better understand how oxygen reaches the brain after cardiac arrest. Researchers are testing neuromonitoring, a technique for monitoring brain activity, to identify patients who struggle with adequate oxygen delivery to the brain. The goal is to determine why this occurs and find ways to improve oxygen delivery. Suitable candidates for this trial include those who have experienced a cardiac arrest lasting over 10 minutes and have significant difficulty responding or waking up afterward. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could enhance future cardiac arrest treatments.

Will I have to stop taking my current medications?

The trial excludes participants who are currently using or are expected to use anticoagulant or antiplatelet medications, so you would need to stop these medications to participate.

What prior data suggests that neuromonitoring is safe for post-cardiac arrest patients?

Research has shown that neuromonitoring tracks brain health after a heart attack. This monitoring provides doctors with crucial information to identify problems early and tailor treatments for each patient. Studies have found that it can help predict recovery outcomes from brain injuries caused by oxygen deprivation.

Specific data on side effects or negative events related to neuromonitoring itself is lacking. This method primarily observes and manages brain activity rather than directly intervening. As a result, it is likely well-tolerated, focusing on gathering information to enhance patient care rather than introducing new drugs or invasive procedures. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about neuromonitoring for hypoxic-ischemic brain injury because it provides real-time insights into brain activity after a cardiac arrest. Unlike traditional treatments, which primarily focus on stabilizing the heart and managing symptoms, neuromonitoring allows doctors to directly observe the brain's response to reduced oxygen levels. This technique could lead to more precise and timely interventions, potentially improving outcomes by preventing further brain damage. By offering a window into the brain's condition, neuromonitoring could revolutionize how we approach treatment decisions in critical care settings.

What evidence suggests that neuromonitoring is effective for hypoxic-ischemic brain injury?

Research has shown that monitoring the brain is crucial in treating brain injuries caused by a lack of oxygen after a heart attack. In this trial, participants will join the Neuromonitoring arm, where this technology identifies problems and customizes treatments for each person. Studies have found that it helps predict recovery outcomes. By using this technology, doctors can assess oxygen delivery to the brain and make adjustments to enhance recovery. In short, it provides real-time information essential for effective treatment after such a serious event. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 19 who've had a cardiac arrest lasting more than 10 minutes and are in a coma or have severe brain function impairment. They must be able to receive invasive monitoring within 72 hours of the event. People with blood clotting issues, on certain blood thinners, or with past severe brain injuries or strokes can't participate.

Inclusion Criteria

I am over 19 and have a low consciousness level after a cardiac arrest.

I had heart monitoring started within 3 days after a cardiac arrest.

My heart has stopped for more than 10 minutes before.

Exclusion Criteria

I am currently using or plan to use blood thinners.

Your blood doesn't clot normally, or you have low platelet levels.

I have had a severe brain injury, bleeding in the brain, or a stroke.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Neuromonitoring

Neuromonitoring is placed after cardiac arrest, and various evaluations are conducted including blood gas analysis and microdialysis measures.

3 days

Continuous monitoring

Follow-up

Participants are monitored for clinical outcomes, including cerebral performance category, at 6 months post-arrest.

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Neuromonitoring

Trial Overview The study aims to understand why some patients can't get enough oxygen into their brains after a cardiac arrest by using advanced neuromonitoring techniques. It will compare those with normal and abnormal oxygen transport to find out what's causing these differences.

How Is the Trial Designed?

Group I: Neuromonitoring arm Experimental Treatment 1 Intervention

Neuromonitoring placed after cardiac arrest

Neuromonitoring is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Neuromonitoring for:

• Monitoring of intracranial pressure and cerebral perfusion in critically ill patients
• Diagnosis and management of seizures and status epilepticus
• Assessment of brain death

Approved in European Union as Neuromonitoring for:

• Monitoring of brain function in patients with traumatic brain injury
• Diagnosis and management of cerebral vasospasm
• Assessment of cerebral autoregulation

Approved in Canada as Neuromonitoring for:

• Monitoring of intracranial pressure and cerebral perfusion in critically ill patients
• Diagnosis and management of seizures and status epilepticus

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Published Research Related to This Trial

Current methods of monitoring intracranial pressure in brain injury patients do not provide information about the oxygenation status of the injured brain, which is crucial for effective treatment.

The article discusses the potential of local tissue oxygen probes as a new monitoring tool that could enhance existing systems by providing real-time data on brain oxygenation, potentially leading to better therapeutic interventions and improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain tissue oxygenation monitoring in acute brain injury. Ng, I., Lee, KK., Wong, J.[2019]

Two promising neuromonitoring techniques for the future are continuous multiparameter local brain tissue monitoring with microprobes and non-invasive local brain tissue oxygenation monitoring using near infrared spectroscopy, both of which have received FDA clearance for clinical use.

These techniques aim to provide less-invasive monitoring that accurately reflects the degree of neurological injury, which is crucial for improving patient outcomes in surgical and intensive care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring for neuroprotection. New technologies for the new millennium. Andrews, RJ.[2004]

Maintaining brain perfusion and oxygenation is crucial for improving patient outcomes in various brain injuries, including traumatic, ischemic, and hemorrhagic types.

The article reviews emerging bedside neuromonitoring techniques that enhance the traditional methods of monitoring intracranial pressure and cerebral perfusion pressure, providing a better understanding of brain physiology and patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain perfusion and oxygenation. Lipp, LL.[2014]

Neuromonitoring is increasingly important in both operating theatres and intensive care units, allowing for continuous or intermittent observation of nervous system functions.

Techniques such as evoked potential recording, intracranial pressure measurement, and EEG recording are crucial for monitoring during surgeries, in intensive care, and for assessing brain death.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromonitoring. Hacke, W.[2019]

Electroencephalogram (EEG) is crucial for detecting seizures and identifying patients with irreversible hypoxic-ischemic brain injury (HIBI), providing valuable guidance for treatment decisions.

Cerebral blood flow (CBF) monitoring and brain biomarkers, such as neuron-specific enolase (NSE), are important for assessing the severity of HIBI and predicting patient outcomes after cardiac arrest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain monitoring after cardiac arrest. Sandroni, C., Skrifvars, MB., Taccone, FS.[2023]

A survey of 52 North American pediatric intensive care units revealed that all institutions measure intracranial pressure and have electroencephalography capabilities, indicating a strong foundation for neuromonitoring in pediatric brain injury cases.

Only 15% of institutions used a multimodality neuromonitoring platform to integrate data from various devices, highlighting a need for standardization in neuromonitoring practices to potentially improve neurological outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Survey of Neuromonitoring Practices in North American Pediatric Intensive Care Units. Kirschen, MP., LaRovere, K., Balakrishnan, B., et al.[2023]

Multiple neuromonitoring tools, including aEEG, NIRS, and biomarker analysis, are essential for assessing brain function and injury in newborns with neonatal encephalopathy (NE), helping to predict long-term outcomes.

Using these tools together can enhance prognostic accuracy and inform treatment decisions, especially in the context of therapeutic hypothermia for NE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bedside and laboratory neuromonitoring in neonatal encephalopathy. Chalak, L., Hellstrom-Westas, L., Bonifacio, S., et al.[2022]

Neonates with hypoxic ischemic encephalopathy (HIE) face serious risks, including death and long-term developmental issues, making effective neuromonitoring essential for diagnosis and prognosis.

Continuous monitoring techniques like cEEG, aEEG, and NIRS provide valuable and complementary insights into brain function and oxygen use, which can help predict outcomes and guide treatment, especially during therapeutic hypothermia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal neuromonitoring techniques in neonates with hypoxic ischemic encephalopathy. Chock, VY., Rao, A., Van Meurs, KP.[2023]

Neuromonitoring in patients with acute cerebral injuries is crucial for detecting early changes in intracranial physiology, which can help prevent secondary brain damage and neurological deterioration.

Various monitoring techniques, including intracranial pressure probes and electrophysiological methods, provide essential information for optimizing medical care in comatose patients, ensuring timely and effective interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Multimodal Neuromonitoring and its Impact on Therapeutic and Diagnostic Decisions in Critical Ill Patients]. Reithmeier, T., Isaak, R., Sanchez-Porres, R.[2019]

Noninvasive neuromonitoring offers several advantages over invasive methods, such as reduced risk of infection and bleeding, no need for surgical installation, and increased mobility, making it a safer option for monitoring brain injuries.

While noninvasive techniques like transcranial ultrasound and electroencephalography show promise, they currently cannot fully replace invasive monitoring methods but can effectively complement them in managing patients with brain injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Neuromonitoring: Current Utility in Subarachnoid Hemorrhage, Traumatic Brain Injury, and Stroke. Vinciguerra, L., Bösel, J.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9994800/

Brain monitoring after cardiac arrest - PMC Neuromonitoring provides essential information to detect complications, individualize treatment and predict prognosis in patients with HIBI.

2. journals.lww.com journals.lww.com/co-criticalcare/fulltext/2023/04000/brain_monitoring_after_cardiac_arrest.5.aspx

Brain monitoring after cardiac arrest Neuromonitoring provides essential information to detect complications, individualize treatment and predict prognosis in patients with HIBI.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0300957219302096

Intracranial pressure and compliance in hypoxic ischemic ... In hypoxic ischemic brain injury (HIBI), increased intracranial pressure (ICP) can ensue from cerebral edema stemming from cytotoxic and vasogenic mechanisms.

4. icm-experimental.springeropen.com icm-experimental.springeropen.com/articles/10.1186/s40635-022-00489-w

Electroencephalographic monitoring of brain activity during ... EEG may represent a useful tool to assess CPR effectiveness. A multimodal approach including other non-invasive tools such as, quantitative ...

5. signavitae.com signavitae.com/articles/10.22514/sv.2022.051

Individualized management objectives for hypoxic ... Hypoxic-ischemic brain injury after cardiac arrest is the main cause of death and neurologic dysfunction in patients after the return of spontaneous circulation ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36762679/

Brain monitoring after cardiac arrest Neuromonitoring provides essential information to detect complications, individualize treatment and predict prognosis in patients with HIBI.

7. ahajournals.org ahajournals.org/doi/10.1161/CIR.0000000000001219

Improving Outcomes After Post–Cardiac Arrest Brain Injury This scientific statement presents a conceptual framework for the pathophysiology of post–cardiac arrest brain injury, explores reasons for previous failure.

8. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-021-03678-3

Monitoring and modifying brain oxygenation in patients at risk ... In this narrative review, we discuss the available means for monitoring the occurrence of brain ischemia in patients at risk of hypoxic ischemic brain injury.