Comparing Hypothermic Temperatures During Hemiarch Surgery

Thoracic Aortic Disease Clinical Trial

— TITAN:COMMENCE  

Official title:

A Randomized Controlled Trial of Mild vs. Moderate Hypothermia on Patient Outcomes in Aortic Hemiarch Surgery With Anterograde Cerebral Perfusion

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02860364
• Other study ID #: 20160408
• Status: Recruiting
• Phase: N/A
• Start date: February 20, 2018
• Est. completion date: September 2025

Study information

• Verified date: February 2024
• Source: Ottawa Heart Institute Research Corporation
• Contact: Jehangir Appoo, MD
• Phone: 403-944-2515
• Email: jappoo[@]ucalgary.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 282
• Est. completion date: September 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years

• Elective aortic hemiarch surgery

• Planned unilateral selective anterograde cardioplegia

• Anticipated lower body arrest time of < 20 minutes

• Able to provide written informed consent

Exclusion Criteria:

• Surgery for acute aortic dissection or emergent operations

• Total arch replacement

• Inability to perform unilateral selective anterograde cerebral perfusion (uSACP)

• Patients with known/documented coagulopathy

• Patients with cold agglutinin disease or those that test positive on routine preop screening

• Pre-existing severe neurological impairment or inability to accurately assess neurocognitive function as determined by the operating surgeon

• Severe carotid disease, defined as: any patient with previously documented carotid stenosis of > 70% (via Doppler ultrasound (US), magnetic resonance angiography (MRA), or computer tomography angiography (CTA)) without neurological deficits; or carotid stenosis > 50% with neurological deficits; or previous carotid endarterectomy or stenting

• Patients in renal failure or currently being treated with renal replacement therapy (RRT) or estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2

• Use of an investigational drug or device at time of enrollment

• Participation in another clinical trial which interferes with performance of the study procedures or assessment of the outcomes

Related Conditions & MeSH terms

• Aortic Diseases
• Thoracic Aortic Disease

Intervention

Procedure:
• Hypothermic circulatory arrest
During cardiac surgery requiring circulatory arrest, the patient's body temperature is lowered significantly to reduce the cellular metabolic rate and reduce ischemic injury.

Locations

Country	Name	City	State
Canada	Dalhousie university	Halifax	Nova Scotia
Canada	Hamilton Health Sciences	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	McGill University Health Centre	Montréal	Quebec
Canada	Montreal Heart Institute	Montréal	Quebec
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Canada	Institut universitaire de cardiologie et de pneumologie de Québec	Québec	Quebec
Canada	Horizon Health Network	Saint John	New Brunswick
Canada	Health Sciences North Research Institute	Sudbury	Ontario
Canada	Fraser Health Authority	Surrey	British Columbia
Canada	University Health Network	Toronto	Ontario
Canada	University of British Columbia	Vancouver	British Columbia
Canada	University of Manitoba	Winnipeg	Manitoba
United States	University of Michigan	Ann Arbor	Michigan
United States	Massachusetts General	Boston	Massachusetts
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Baylor Scott & White Medical Center	Dallas	Texas
United States	Duke University Hospital	Durham	North Carolina
United States	Mount Sinai Hospital	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	The Valley Hospital	Ridgewood	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Heart Institute Research Corporation

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite endpoint of neurologic and acute kidney injury	The primary objective of this study is to determine whether mild hypothermia (32°C) during aortic hemiarch surgery using unilateral selective anterograde cerebral perfusion (uSACP), is superior to moderate hypothermia (26°C) in reducing the composite endpoint of neurologic and acute kidney injury.	Up to 90 days after surgery.
Secondary	Rates of Neurologic Injury	Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to incidence of neurologic injury, including transient ischemic attack (TIA) and permanent neurological dysfunction (PND) or stroke.	Up to 90 days after surgery.
Secondary	Incidence of Silent Strokes	Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the incidence of silent strokes, defined as infarctions identified during magnetic resonance imaging (MRI) in patients without neurologic symptoms.	Up to 90 days after surgery.
Secondary	Incidence of Acute Kidney Injury (AKI)	Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the incidence of acute kidney injury (AKI), defined as Stage 1 or greater using the KDIGO criteria. Using the KDIGO criteria, Stage 1 AKI is defined as an increase in serum creatinine of 1.5-1.9x the baseline or an increase >= 27umol/L with urine output <0.5mL/kg/hour for 6-12 hours.	Up to 90 days after surgery.
Secondary	Incidence of Delirium	Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the incidence of delirium, using the Confusion Assessment Method (CAM). The Confusion Assessment Method defines delirium as the presence of acute changes in mental status with fluctuating course, plus inattention and the presence of either disorganized thinking OR altered level of consciousness.	Up to 90 days after surgery.
Secondary	Death	Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the incidence of death	Up to 90 days after surgery.
Secondary	Evaluate differences in the duration of cardiopulmonary bypass used in patients who receive mild or moderate hypothermic circulatory arrest during aortic hemiarch surgery	Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the length of time that the patient remains on cardiopulmonary bypass.	During the index procedure
Secondary	Rates of Mediastinal re-exploration for bleeding	Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the rates of mediastinal re-exploration (re-operation) for bleeding.	Up to 90 days after surgery.
Secondary	Incidence and quantity of perioperative blood transfusions	Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the number and quantity of perioperative blood transfusions	Up to 90 days after surgery.
Secondary	Incidence of prolonged Mechanical Ventilation	Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the duration of mechanical ventilation. Mechanical ventilation will be defined as use of a mechanical ventilator =48 hours.	Up to 90 days after surgery.
Secondary	Perioperative Myocardial Infarction	Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the incidence of perioperative myocardial infarction. This will be clinically diagnosed using a combination of electrocardiographic (new Q wave on 12 lead ECG) and/or biochemical (TnI > 45 ng/L) markers.	Up to 48 hours after surgery.
Secondary	Length of Stay	Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the duration of a patient's stay in the intensive care unit and on the hospital ward.	Up to 90 days after surgery.
Secondary	Quality of life (SF-12)	Comparison of mild (32°C) vs moderate (26°C) hypothermia in aortic hemiarch surgery with respect to the patient's quality of life measured using the Short Form (SF) 12 questionnaire.	Up to 90 days after surgery.