Hypothermia During Aortic Surgery

(TITAN:COMMENCE Trial)

Recruiting at 20 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

Trial Summary

What is the purpose of this trial?

Hypothermic circulatory arrest is an important surgical technique, allowing complex aortic surgeries to be performed safely. Hypothermic circulatory arrest provides protection to cerebral and visceral organs, but may result in longer cardiopulmonary bypass times during surgery, increased risks of bleeding, inflammation, and neuronal injury. To manage these consequences, a trend towards warmer core body temperatures during circulatory arrest has emerged. This trial will randomize patients to either mild (32°C) or moderate (26°C) hypothermia during aortic hemiarch surgery to determine if mild hypothermia reduces the length of cardiopulmonary bypass time and other key measures of morbidity and mortality.

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 data supports the effectiveness of the treatment Hypothermic circulatory arrest during aortic surgery?

Research shows that deep hypothermic circulatory arrest (DHCA) can protect the brain during aortic surgery by reducing the risk of brain damage. Additionally, it may help maintain better function of vital organs and the spinal cord during surgery. ^{1 2 3 4 5}

Is hypothermic circulatory arrest safe for humans during aortic surgery?

Studies suggest that hypothermic circulatory arrest (HCA), including deep hypothermic circulatory arrest (DHCA), is generally safe for use in aortic surgery, with some research indicating it does not adversely affect cognitive abilities or daily activities. However, there is some controversy, as prolonged use may increase risks, and the safety can depend on the specific temperature management used during the procedure. ^{1 2 3 5 6}

What makes hypothermic circulatory arrest unique for aortic surgery?

Hypothermic circulatory arrest (HCA) is unique because it involves cooling the body to very low temperatures to protect the brain and other organs during aortic surgery, allowing surgeons to stop blood flow temporarily. This method is different from other treatments as it uses deep hypothermia (very low body temperature) to reduce metabolic activity and protect the brain, which is not typically done in other surgical procedures. ^{1 2 3 5 7}

Research Team

Munir Boodhwani, MD

Principal Investigator

Ottawa Heart Institute Research Corporation

Eligibility Criteria

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 18 years old or older.

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.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. Singapore pubmed.ncbi.nlm.nih.gov

Deep hypothermic circulatory arrest in adults undergoing aortic surgery: local experience. [2022]

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

Resection of the descending thoracic aorta: outcomes after use of hypothermic circulatory arrest. [2022]

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

Optimal temperature management in aortic arch surgery: A systematic review and network meta-analysis. [2023]

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

Remote Ischemic Preconditioning Attenuates Oxidative Stress during Cardiopulmonary Bypass. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Cerebral metabolic suppression during hypothermic circulatory arrest in humans. [2019]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Deep hypothermic circulatory arrest in patients with high cognitive needs: full preservation of cognitive abilities. [2016]

7. United States 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. [2023]