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Perioperative Hypothermia and Myocardial Injury After Non-cardiac Surgery (PROTECT)

Primary Purpose

Perioperative Care, Surgery--Complications, Hypothermia; Anesthesia

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
aggressive warming
routine thermal management
Sponsored by
The Cleveland Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Perioperative Care focused on measuring Hypothermia, Intraoperative warming, non-cardiac surgery, myocardial injury

Eligibility Criteria

45 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Scheduled for major noncardiac surgery expected to last 2-6 hours;
  • Having general anesthesia;
  • Expected to require at least overnight hospitalization;
  • Expected to have >50% of the anterior skin surface available for warming;

  • Have at least one of the following risk factors:

    a. Age over 65 years; b. History of peripheral vascular surgery; c. History of coronary artery disease; d. History of stroke or transient ischemic attack; e. Serum creatinine >175 µmal/L (>2.0 mg/dl); f. Diabetes requiring medication; e. Hypertension requiring medication; g. Current smoking.

Exclusion Criteria:

  • Have a clinically important coagulopathy in the judgement of the attending anesthesiologist;
  • Are septic (clinical diagnosis by the attending anesthesiologist);
  • Body mass index exceeding 30 kg/m2;
  • End-stage renal disease requiring dialysis;
  • Surgeon believes patient to be at particular infection risk.

Sites / Locations

  • Cleveland Clinic Foundation
  • PUMCH
  • West China Hospital Sichuan Univeristy
  • Guangdong General Hospital
  • Chinese University of Hong Kong
  • Queen Mary Hospital
  • Nanjing Drum Tower Hospital
  • FDSCC (Fudan University Shanghai
  • Shanghai Chest Hospital
  • Shanghai Oriental Hospital
  • Shanghai Zhongshan Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Routine thermal management

Aggressive thermal management

Arm Description

Patients assigned to routine thermal management will not be pre-warmed and ambient intraoperative temperature will be maintained near 20°C per routine. Only transfused blood will be warmed. An Multi-Position Upper Body Warming Blanket forced-air cover will be positioned over an appropriate non-operative site, but will not initially be activated. Should core temperature decrease to 35.5°C, the warmer will be activated as necessary to prevent core temperature from decreasing further.

Patients assigned to aggressive warming will be pre-warmed with a full-body Bair Hugger or Bair Paws cover for ≈30 minutes before induction of anesthesia. The warmer will initially be set to "high" which corresponds to ≈43°C. It will be subsequently adjusted to make patients feel warm, but not uncomfortably so. Patients will be aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C, using an Multi-Position Upper Body and Full Access Underbody Warming Blankets forced-air covers when clinically practical. All intravenous fluids will be warmed to body temperature.

Outcomes

Primary Outcome Measures

Number of Participants With a Composite Outcome Consisted of Myocardial Injury After Non-cardiac Surgery (MINS), Non-fatal Cardiac Arrest, and All-cause Mortality
The primary outcome was a composite of myocardial injury after non-cardiac surgery, non-fatal cardiac arrest, and all-cause mortality within 30 days of surgery. Myocardial injury was diagnosed when available troponin concentrations exceeded generation-specific and type-specific thresholds and were apparently of ischaemic origin (ie, no other obvious cause for artifactual elevation). We used the following thresholds based on available literature at time of adjudication: 1) non-high-sensitivity (fourth-generation) troponin T ≥0.03 ng/ml2; 2) high-sensitivity troponin T ≥65 ng/L; or high-sensitivity troponin T 20-64 ng/L and an increase ≥5 ng/L from baseline3; 3) high-sensitivity troponin I (Abbott assay) is ≥75 ng/L4; 4) high-sensitivity troponin I (Siemens assay) is ≥60 ng/L5; or, 5) troponin I (other assays) greater than local 99th percentiles. Myocardial infarction diagnosis required both troponin elevation and at least one diagnostic symptom or sign.

Secondary Outcome Measures

Deep or Organ-space Surgical Site Infection
Surgical site infection is defined by US Centers for Disease Control and Prevention criteria. It is consisted of superficial infection, deep infection, and organ-space infection. Superficial infection: Infection involves only skin or subcutaneous tissue of the incision. Deep infection: Infection appears to be related to the operation and infection involves deep soft tissues (e.g., fascial and muscle layers) of the incision. Organ-space infection: Infection involves any part of the anatomy (e.g., organs or spaces), other than the incision, which was opened or manipulated during an operation.
Number of Patients Requiring Intraoperative Transfusion
intraoperative transfusion will be yes if this patient received more than 0 unit of red blood cells.
Duration of Hospitalization
The length of hospital stay in days, censored at 30 days
Readmission
Readmission to a hospital within a month of surgery

Full Information

First Posted
April 7, 2017
Last Updated
July 11, 2023
Sponsor
The Cleveland Clinic
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1. Study Identification

Unique Protocol Identification Number
NCT03111875
Brief Title
Perioperative Hypothermia and Myocardial Injury After Non-cardiac Surgery
Acronym
PROTECT
Official Title
Perioperative Hypothermia and Myocardial Injury After Non-cardiac Surgery
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
March 27, 2017 (Actual)
Primary Completion Date
March 16, 2021 (Actual)
Study Completion Date
May 17, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Cleveland Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
We propose to test the hypothesis that aggressive warming reduces the incidence of major cardiovascular complications, compared to routine care. Half of the participants will be randomly assigned to routine care (core temperature ≈35.5°C), while the other half will receive aggressive warming (>37°C core temperature) in a multi-center trial.
Detailed Description
Hypothermia increases sympathetic activation, promotes tachycardia, and causes hypertension - all of which may increase the risk of myocardial injury. Moderate perioperative hypothermia is now uncommon, but mild hyperthermia (≈35.5°C) remains common. Whether aggressive warming to a truly normothermic level (≈37°C) improves outcomes remains unknown.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Perioperative Care, Surgery--Complications, Hypothermia; Anesthesia, Myocardial Injury
Keywords
Hypothermia, Intraoperative warming, non-cardiac surgery, myocardial injury

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Masking Description
To maintain blinding, the anesthesia record will be sealed in an opaque envelope before patients leave the post-anesthesia care unit. The envelope will be marked "Do not open until [date 35 days after surgery]." Some hospitals will have electronic records; in those cases, we will ask investigators evaluating postoperative outcomes not to access the anesthesia record.
Allocation
Randomized
Enrollment
5056 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Routine thermal management
Arm Type
Active Comparator
Arm Description
Patients assigned to routine thermal management will not be pre-warmed and ambient intraoperative temperature will be maintained near 20°C per routine. Only transfused blood will be warmed. An Multi-Position Upper Body Warming Blanket forced-air cover will be positioned over an appropriate non-operative site, but will not initially be activated. Should core temperature decrease to 35.5°C, the warmer will be activated as necessary to prevent core temperature from decreasing further.
Arm Title
Aggressive thermal management
Arm Type
Experimental
Arm Description
Patients assigned to aggressive warming will be pre-warmed with a full-body Bair Hugger or Bair Paws cover for ≈30 minutes before induction of anesthesia. The warmer will initially be set to "high" which corresponds to ≈43°C. It will be subsequently adjusted to make patients feel warm, but not uncomfortably so. Patients will be aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C, using an Multi-Position Upper Body and Full Access Underbody Warming Blankets forced-air covers when clinically practical. All intravenous fluids will be warmed to body temperature.
Intervention Type
Device
Intervention Name(s)
aggressive warming
Intervention Description
Patients will be pre-warming 30 minutes before induction of anesthesia and aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C.
Intervention Type
Device
Intervention Name(s)
routine thermal management
Intervention Description
A forced-air cover will be positioned but will not initially be activated. The warmer will be activated when core temperature decrease to 35.5°C.
Primary Outcome Measure Information:
Title
Number of Participants With a Composite Outcome Consisted of Myocardial Injury After Non-cardiac Surgery (MINS), Non-fatal Cardiac Arrest, and All-cause Mortality
Description
The primary outcome was a composite of myocardial injury after non-cardiac surgery, non-fatal cardiac arrest, and all-cause mortality within 30 days of surgery. Myocardial injury was diagnosed when available troponin concentrations exceeded generation-specific and type-specific thresholds and were apparently of ischaemic origin (ie, no other obvious cause for artifactual elevation). We used the following thresholds based on available literature at time of adjudication: 1) non-high-sensitivity (fourth-generation) troponin T ≥0.03 ng/ml2; 2) high-sensitivity troponin T ≥65 ng/L; or high-sensitivity troponin T 20-64 ng/L and an increase ≥5 ng/L from baseline3; 3) high-sensitivity troponin I (Abbott assay) is ≥75 ng/L4; 4) high-sensitivity troponin I (Siemens assay) is ≥60 ng/L5; or, 5) troponin I (other assays) greater than local 99th percentiles. Myocardial infarction diagnosis required both troponin elevation and at least one diagnostic symptom or sign.
Time Frame
From the end of surgery to 30 days after surgery
Secondary Outcome Measure Information:
Title
Deep or Organ-space Surgical Site Infection
Description
Surgical site infection is defined by US Centers for Disease Control and Prevention criteria. It is consisted of superficial infection, deep infection, and organ-space infection. Superficial infection: Infection involves only skin or subcutaneous tissue of the incision. Deep infection: Infection appears to be related to the operation and infection involves deep soft tissues (e.g., fascial and muscle layers) of the incision. Organ-space infection: Infection involves any part of the anatomy (e.g., organs or spaces), other than the incision, which was opened or manipulated during an operation.
Time Frame
From the end of surgery to 30 days after surgery
Title
Number of Patients Requiring Intraoperative Transfusion
Description
intraoperative transfusion will be yes if this patient received more than 0 unit of red blood cells.
Time Frame
From surgery start to surgery end
Title
Duration of Hospitalization
Description
The length of hospital stay in days, censored at 30 days
Time Frame
From the day of surgery to the day of discharge, or 30 days after surgery if the patients is still hospitalized
Title
Readmission
Description
Readmission to a hospital within a month of surgery
Time Frame
From the end of surgery to 30 days after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Scheduled for major noncardiac surgery expected to last 2-6 hours; Having general anesthesia; Expected to require at least overnight hospitalization; Expected to have >50% of the anterior skin surface available for warming; Have at least one of the following risk factors: a. Age over 65 years; b. History of peripheral vascular surgery; c. History of coronary artery disease; d. History of stroke or transient ischemic attack; e. Serum creatinine >175 µmal/L (>2.0 mg/dl); f. Diabetes requiring medication; e. Hypertension requiring medication; g. Current smoking. Exclusion Criteria: Have a clinically important coagulopathy in the judgement of the attending anesthesiologist; Are septic (clinical diagnosis by the attending anesthesiologist); Body mass index exceeding 30 kg/m2; End-stage renal disease requiring dialysis; Surgeon believes patient to be at particular infection risk.
Facility Information:
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
PUMCH
City
Beijing
Country
China
Facility Name
West China Hospital Sichuan Univeristy
City
Chengdu
Country
China
Facility Name
Guangdong General Hospital
City
Guangzhou
Country
China
Facility Name
Chinese University of Hong Kong
City
Hong Kong
Country
China
Facility Name
Queen Mary Hospital
City
Hong Kong
Country
China
Facility Name
Nanjing Drum Tower Hospital
City
Nanjing
Country
China
Facility Name
FDSCC (Fudan University Shanghai
City
Shanghai
Country
China
Facility Name
Shanghai Chest Hospital
City
Shanghai
Country
China
Facility Name
Shanghai Oriental Hospital
City
Shanghai
Country
China
Facility Name
Shanghai Zhongshan Hospital
City
Shanghai
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Investigators are welcome to propose collaborative analyses.
IPD Sharing Time Frame
Upon publication of the main paper.
IPD Sharing Access Criteria
Via corresponding author,
Citations:
PubMed Identifier
35390321
Citation
Sessler DI, Pei L, Li K, Cui S, Chan MTV, Huang Y, Wu J, He X, Bajracharya GR, Rivas E, Lam CKM; PROTECT Investigators. Aggressive intraoperative warming versus routine thermal management during non-cardiac surgery (PROTECT): a multicentre, parallel group, superiority trial. Lancet. 2022 May 7;399(10337):1799-1808. doi: 10.1016/S0140-6736(22)00560-8. Epub 2022 Apr 4.
Results Reference
derived

Learn more about this trial

Perioperative Hypothermia and Myocardial Injury After Non-cardiac Surgery

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