Comparing Hypothermic Temperatures During Hemiarch Surgery (TITAN:COMMENCE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Thoracic Aortic Disease
• Intervention / Treatment: Procedure: Hypothermic circulatory arrest

• Study Type: Interventional
• Enrollment (Estimated): 282
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jehangir Appoo, MD; Phone Number: 403-944-2515; Email: jappoo@ucalgary.ca
• Study Contact Backup: Name: Alice Black, BSc; Phone Number: 613-696-7230; Email: alblack@ottawaheart.ca

Study Locations

• Canada
  • British Columbia
    • Surrey, British Columbia, Canada, V3T 0H1
      • Recruiting
      • Fraser Health Authority
      • Principal Investigator: Daniel Wong, MD
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Not yet recruiting
      • University of British Columbia
      • Principal Investigator: Joel Price, MD
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • Not yet recruiting
      • University of Manitoba
      • Principal Investigator: Michael Yamashita, MD
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Recruiting
      • Horizon Health Network
      • Principal Investigator: Zlatko Pozeg, MD
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • Not yet recruiting
      • Dalhousie University
      • Principal Investigator: Christine Herman, MD
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Recruiting
      • Hamilton Health Sciences
      • Principal Investigator: Richard Whitlock, MD
    • London, Ontario, Canada, N6A 5A5
      • Recruiting
      • London Health Sciences Centre
      • Principal Investigator: Michael Chu, MD
    • Ottawa, Ontario, Canada, K1Y 4W7
      • Recruiting
      • University of Ottawa Heart Institute
      • Principal Investigator: Munir Boodhwani
    • Sudbury, Ontario, Canada, P3E 2H3
      • Recruiting
      • Health Sciences North Research Institute
      • Principal Investigator: Rony Atoui, MD
    • Toronto, Ontario, Canada, M5G 2N2
      • Recruiting
      • University Health Network
      • Principal Investigator: Maral Ouzounian, MD
  • Quebec
    • Montréal, Quebec, Canada, H4A 3J1
      • Recruiting
      • McGill University Health Centre
      • Principal Investigator: Kevin Lachapelle, MD
    • Montréal, Quebec, Canada, H1T 1C8
      • Recruiting
      • Montreal Heart Institute
      • Principal Investigator: Philippe Demers
    • Québec, Quebec, Canada, G1V 4G5
      • Recruiting
      • Institut Universitaire de Cardiologie et de Pneumologie de Quebec
      • Principal Investigator: François Dagenais, MD
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General
      • Principal Investigator: Arminder Jassar, MD
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Principal Investigator: Himanshu Patel, MD
  • New Jersey
    • Ridgewood, New Jersey, United States, 07450
      • Recruiting
      • The Valley Hospital
      • Sub-Investigator: Juan Grau, MD
      • Principal Investigator: Jabagi Habib, MD
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai Hospital
      • Principal Investigator: Ismail El-Hamamsy, MD
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Hospital
      • Principal Investigator: George Hughes, MD
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University Medical Center
      • Principal Investigator: Jovan Bovinovski, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Principal Investigator: Nimesh Desai, MD
  • Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Baylor Scott & White Medical Center
      • Principal Investigator: William Brinkman, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mild Hypothermic Circulatory Arrest; During aortic hemiarch surgery, mild hypothermia (32°C) will be used during circulatory arrest.	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.
Active Comparator: Moderate Hypothermic Circulatory Arrest; During aortic hemiarch surgery, moderate hypothermia (26°C) will be used during circulatory arrest.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
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.

Collaborators and Investigators

• Sponsor: Ottawa Heart Institute Research Corporation
• Investigators: Principal Investigator: Munir Boodhwani, MD, Ottawa Heart Institute Research Corporation

Publications and helpful links

General Publications

• Jabagi H, Wells G, Boodhwani M. COMMENCE trial (Comparing hypOtherMic teMperaturEs duriNg hemiarCh surgEry): a randomized controlled trial of mild vs moderate hypothermia on patient outcomes in aortic hemiarch surgery with anterograde cerebral perfusion. Trials. 2019 Dec 9;20(1):691. doi: 10.1186/s13063-019-3713-9.

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2018
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: August 4, 2016
• First Submitted That Met QC Criteria: August 8, 2016
• First Posted (Estimated): August 9, 2016

Study Record Updates

• Last Update Posted (Actual): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Aortic Diseases
• Other Study ID Numbers: 20160408

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be made available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No