Hypothermia During Aortic Surgery

(TITAN:COMMENCE Trial)

Recruiting at 24 trial locations

Overseen By Alice Black, BSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ottawa Heart Institute Research Corporation

Must not be taking: Investigational drugs

Disqualifiers: Acute aortic dissection, Coagulopathy, Severe carotid disease, Renal failure, 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

Duration: During the index procedure

282 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates the optimal use of a cooling technique called hypothermic circulatory arrest during aortic surgery to protect organs while minimizing risks. Researchers aim to determine if milder cooling (32°C) during surgery is safer and more effective than moderate cooling (26°C). The trial includes individuals requiring planned aortic hemiarch surgery who can consent to the study terms. Participants will be randomly assigned to one of the two cooling methods to identify the superior approach. As an unphased trial, this study allows participants to contribute to innovative research that could enhance surgical outcomes.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that hypothermic circulatory arrest is safe for aortic surgery?

Studies have shown that cooling the body to 32°C during aortic surgery, known as mild hypothermic circulatory arrest, is safe for patients. Research indicates that patients tolerate this method well and do not experience serious problems. For example, one study found that mild hypothermia is safe in the short term when combined with techniques to protect the brain.

Another study compared mild and moderate cooling and found that mild hypothermia is just as safe as traditional methods. This suggests that patients can undergo surgery with mild hypothermia without extra risk.

Overall, these findings suggest that using mild hypothermia during surgery might safely protect the brain and other organs. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about hypothermic circulatory arrest during aortic surgery because it offers a unique approach to protecting the brain and vital organs. Unlike the standard practice of using moderate hypothermia at 26°C, this trial examines both mild hypothermia at 32°C and moderate hypothermia, potentially providing insights into the optimal temperature for patient safety and outcomes. By comparing these two levels of hypothermia, researchers hope to determine which approach minimizes complications and enhances recovery, potentially leading to refined surgical protocols that improve patient care during complex aortic surgeries.

What evidence suggests that mild hypothermia might be an effective treatment for reducing cardiopulmonary bypass time during aortic surgery?

This trial will compare mild hypothermic circulatory arrest, where the body is cooled to 32°C, with moderate hypothermic circulatory arrest, where the body is cooled to 26°C, during aortic surgeries. Research has shown that cooling the body to 32°C can be done safely. Studies have found that this method, especially when combined with a technique that maintains blood flow to the brain, leads to good short-term results. One study discovered that mild cooling is as effective as deeper cooling methods but may carry less risk. In some cases, using mild to moderate cooling has been linked to a lower chance of death and stroke after surgery. Overall, evidence suggests that mild cooling can be a safe and effective option for complex aortic surgeries. ^{1 2 3 6 7}

Who Is on the Research Team?

Munir Boodhwani, MD

Principal Investigator

Ottawa Heart Institute Research Corporation

Are You a Good Fit for This Trial?

This trial is for adults over 18 planning to undergo elective aortic hemiarch surgery with an expected lower body arrest time under 20 minutes. Participants must be able to consent and not have severe neurological issues, coagulopathies, severe carotid disease, renal failure, or cold agglutinin disease.

Inclusion Criteria

I am scheduled for elective surgery on the upper part of my aorta.

My surgery is expected to stop blood flow in my lower body for less than 20 minutes.

I am scheduled for a specific heart surgery technique.

Exclusion Criteria

I have had surgery for a sudden tear in my aorta.

I have had a total arch replacement surgery.

You have a known blood clotting disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo aortic hemiarch surgery with either mild (32°C) or moderate (26°C) hypothermia during circulatory arrest

During the index procedure

Follow-up

Participants are monitored for safety and effectiveness after surgery, including assessments of quality of life, incidence of complications, and length of hospital stay

Up to 90 days

What Are the Treatments Tested in This Trial?

Interventions

• Hypothermic circulatory arrest

Trial Overview The study compares two levels of hypothermia during surgery: mild (32°C) versus moderate (26°C). It aims to see if milder temperatures can shorten cardiopulmonary bypass times and reduce complications related to bleeding, inflammation, and brain injury.

How Is the Trial Designed?

Group I: Mild Hypothermic Circulatory Arrest Experimental Treatment 1 Intervention

During aortic hemiarch surgery, mild hypothermia (32°C) will be used during circulatory arrest.

Group II: Moderate Hypothermic Circulatory Arrest Active Control 1 Intervention

During aortic hemiarch surgery, moderate hypothermia (26°C) will be used during circulatory arrest.

Hypothermic circulatory arrest is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Deep Hypothermic Circulatory Arrest for:

• Aortic arch repair
• Thoracoabdominal aorta surgery
• Giant cerebral aneurysm repair
• Cerebral arteriovenous malformation resection

Approved in United States as Deep Hypothermic Circulatory Arrest for:

• Aortic arch repair
• Thoracoabdominal aorta surgery
• Giant cerebral aneurysm repair
• Cerebral arteriovenous malformation resection
• Pulmonary thromboendarterectomy

Approved in Canada as Deep Hypothermic Circulatory Arrest for:

• Aortic arch repair
• Thoracoabdominal aorta surgery
• Giant cerebral aneurysm repair
• Cerebral arteriovenous malformation resection

Who Is Running the Clinical Trial?

Ottawa Heart Institute Research Corporation

Lead Sponsor

Trials

200

Recruited

95,800+

Published Research Related to This Trial

A study of 29 high-cognitive patients who underwent thoracic aortic surgery using deep hypothermic circulatory arrest (DHCA) showed no significant cognitive decline post-surgery, indicating that DHCA is a safe cerebral protection strategy.

Functional outcomes, including daily activities and work performance, were similar between patients who underwent surgery with DHCA and those who did not, suggesting that DHCA does not adversely affect cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep hypothermic circulatory arrest in patients with high cognitive needs: full preservation of cognitive abilities. Percy, A., Widman, S., Rizzo, JA., et al.[2016]

In a multicenter randomized trial involving 282 patients undergoing aortic arch surgery, low-moderate hypothermia (20.1-24.0°C) was found to be noninferior to deep hypothermia (≤20.0°C) regarding global cognitive change scores four weeks post-surgery, indicating it is a safe alternative.

While low-moderate hypothermia showed similar cognitive outcomes to deep hypothermia, structured verbal memory was better preserved in the deep hypothermia group, suggesting that further research is needed to optimize brain protection during hypothermic circulatory arrest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest Trial (GOT ICE): A Randomized Clinical Trial Comparing Outcomes After Aortic Arch Surgery. Hughes, GC., Chen, EP., Browndyke, JN., et al.[2023]

In a study of 37 adults undergoing hypothermic circulatory arrest (HCA), it was found that the human cerebral metabolic rate remains at 17% of baseline even at 15 degrees Celsius, indicating that metabolism is still active during hypothermia.

The research suggests that the safe duration for HCA at 15 degrees Celsius is only 29 minutes, which is shorter than current practices, highlighting the need for potentially lower temperatures and shorter intervals to ensure adequate brain protection during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral metabolic suppression during hypothermic circulatory arrest in humans. McCullough, JN., Zhang, N., Reich, DL., et al.[2019]

In a network meta-analysis of 34 studies involving 12,370 patients, moderate hypothermic circulatory arrest (MHCA) and mild hypothermic circulatory arrest (mild HCA) were associated with lower operative mortality and reduced risk of postoperative stroke compared to deep hypothermic circulatory arrest (DHCA).

Specifically, DHCA was linked to a significantly higher incidence of stroke (odds ratio 1.46 compared to MHCA and 1.50 compared to mild HCA) and higher operative mortality (odds ratio 1.71 compared to mild HCA), indicating that less extreme cooling strategies may be safer for patients undergoing aortic arch surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal temperature management in aortic arch surgery: A systematic review and network meta-analysis. Abjigitova, D., Notenboom, ML., Veen, KM., et al.[2023]

In a study involving 52 piglets undergoing deep hypothermic circulatory arrest (DHCA), remote ischemic preconditioning (RIPC) significantly reduced oxidative stress, as indicated by lower serum levels of 8-hydroxydeoxyguanosine (8-OHdG) compared to the control group.

The RIPC group showed lower 8-OHdG concentrations both after the cooling phase and 8 hours post-surgery, suggesting that RIPC can provide protective effects against neurological damage during complex heart surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remote Ischemic Preconditioning Attenuates Oxidative Stress during Cardiopulmonary Bypass. Arvola, O., Haapanen, H., Herajärvi, J., et al.[2019]

Deep hypothermic circulatory arrest (DHCA) was evaluated in 59 patients undergoing aortic surgery, showing it to be an effective method for cerebral protection, with a postoperative irreversible neurologic deficit rate of 13.6%.

The study found a 22% intra-hospital mortality rate, with longer circulatory arrest times associated with higher mortality, suggesting that optimizing surgical techniques and experience could improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep hypothermic circulatory arrest in adults undergoing aortic surgery: local experience. Chong, SY., Chow, MY., Kang, DS., et al.[2022]

In a study of 132 patients undergoing descending thoracic aortic resection using hypothermic circulatory arrest (HCA), the 30-day mortality rate was 6.0%, indicating a relatively low risk of death associated with this procedure.

The use of HCA was linked to acceptable rates of neurological events (6.8% stroke and 4.5% permanent paralysis), suggesting that while there are risks, the technique may help preserve organ function during complex surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resection of the descending thoracic aorta: outcomes after use of hypothermic circulatory arrest. Patel, HJ., Shillingford, MS., Mihalik, S., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9073794/

Comparison of short-term outcomes of mild and moderate ... Current data suggest that the mild hypothermia strategy can be safely applied for AAS. Keywords: Mild hypothermic circulatory arrest (Mi-HCA), aortic arch ...

2. jtd.amegroups.org jtd.amegroups.org/article/view/91010/html

Short-term outcomes of mild (≥30 °C) vs. moderate ... The short-term outcomes and safety of mild hypothermic circulatory arrest (Mi-HCA), in combination with antegrade cerebral perfusion (ACP), in aortic arch ...

3. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.067022

A Randomized Clinical Trial Comparing Outcomes After ... This randomized multicenter study evaluating arch surgery HCA temperature strategies found low-moderate hypothermia noninferior to traditional deep hypothermia.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10098497/

Optimal temperature management in aortic arch surgery In the included studies, the moderate to mild hypothermia strategies were associated with decreased operative mortality and the risk of postoperative stroke.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0022522321015555

Optimal circulatory arrest temperature for aortic hemiarch ... This study demonstrates an early survival benefit for patients cooled between 25 and 28°C, with the greatest reduction in the odds of mortality at 27°C.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1053077023007139

Hypothermic Circulatory Arrest in Adult Aortic Arch Surgery Hypothermic circulatory arrest (HCA) enables a safe approach during open aortic arch surgeries. Additionally, HCA provides neuroprotection by reducing cerebral ...

7. annalsthoracicsurgery.org annalsthoracicsurgery.org/article/S0003-4975(15)00062-4/pdf

Moderate Versus Deep Hypothermic Circulatory Arrest for ... We hypothesized that MHCA with an ACP strategy provides outcomes that are equivalent to our traditional practice of DHCA with RCP for elec- tive aortic hemiarch ...