Perioperative CarePROTECTNCT03111875
Perioperative Hypothermia and Myocardial Injury After Non-cardiac Surgery
A study testing aggressive warming and routine thermal management in people with Perioperative Care and Surgery--Complications, run by The Cleveland Clinic at 11 sites in 2 countries.
Trial 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)… Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Perioperative Care, Surgery--Complications, Hypothermia; Anesthesia
- What is being tested?
- aggressive warming and routine thermal management
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5,056 participants
- Where
- 11 sitesin 2 countries
- Study dates
- 27 Mar 2017to 17 May 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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.
Who cannot join
- 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.
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
China10 sites
PUMCH
Beijing
West China Hospital Sichuan Univeristy
Chengdu
Guangdong General Hospital
Guangzhou
Chinese University of Hong Kong
Hong Kong
Queen Mary Hospital
Hong Kong
Nanjing Drum Tower Hospital
Nanjing
FDSCC (Fudan University Shanghai
Shanghai
Shanghai Chest Hospital
Shanghai
Shanghai Oriental Hospital
Shanghai
Shanghai Zhongshan Hospital
Shanghai
About this study
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.
Read the 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.
- Being tested
- aggressive warming, routine thermal management
- Keywords
- Hypothermia, Intraoperative warming, non-cardiac surgery, myocardial injury
- Medical subject headings
- Hypothermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
aggressive warmingDevice
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.
routine thermal managementDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Routine thermal management | Active comparator | 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. Receives: Device: routine thermal management |
| Aggressive thermal management | Experimental | 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. Receives: Device: aggressive warming |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From the end of surgery to 30 days after surgery
Secondary outcomes (4)
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.
Measured: From the end of surgery to 30 days after surgery
Number of Patients Requiring Intraoperative Transfusion
intraoperative transfusion will be yes if this patient received more than 0 unit of red blood cells.
Measured: From surgery start to surgery end
Duration of Hospitalization
The length of hospital stay in days, censored at 30 days
Measured: From the day of surgery to the day of discharge, or 30 days after surgery if the patients is still hospitalized
Readmission
Readmission to a hospital within a month of surgery
Measured: From the end of surgery to 30 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2017
- Study start27 Mar 2017
- Primary completion16 Mar 2021
- Study completion17 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Perioperative CareStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 5,056 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, d sessler, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03111875
- Sponsor's protocol ID
- 16-1017
- Acronym
- PROTECT
- Status last verified
- Jul 2023
- First submitted
- 7 Apr 2017
- Last updated
- 1 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Investigators are welcome to propose collaborative analyses.
Publications
Song S, Pei L, Chen H, Zhang Y, Sun C, Yi J, Huang Y. Analysis of hospital and payer costs of care: aggressive warming versus routine warming in abdominal major surgery. Front Public Health. 2023 Nov 2;11:1256254. doi: 10.3389/fpubh.2023.1256254. eCollection 2023.
PubMed 38026375Sessler 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.
PubMed 35390321
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Perioperative Hypothermia and Myocardial Injury After Non-cardiac Surgery
- ClinicalTrials.gov ID
- NCT03111875
- Acronym / sponsor ID
- PROTECT / 16-1017
- Keywords
- Hypothermia, Intraoperative warming, non-cardiac surgery, myocardial injury
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5,056 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- 27 Mar 2017 (actual)
- Primary completion
- 16 Mar 2021 (actual)
- Study completion
- 17 May 2022 (actual)
- First posted
- 13 Apr 2017 (actual)
- Results
- Posted 1 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Routine thermal management | Active comparator | Device: routine thermal managementPatients 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. |
| Aggressive thermal management | Experimental | Device: aggressive warmingPatients 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. |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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:
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| aggressive warmingPatients 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. | Device | Aggressive thermal management |
| routine thermal managementA 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. | Device | Routine thermal management |
Primary outcome
Number of Participants With a Composite Outcome Consisted of Myocardial Injury After Non-cardiac Surgery (MINS), Non-fatal Cardiac Arrest, and All-cause Mortality
Time frame: From the end of surgery to 30 days after surgery
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.
4 secondary outcomes
Deep or Organ-space Surgical Site Infection
Time frame: From the end of surgery to 30 days after surgery
Number of Patients Requiring Intraoperative Transfusion
Time frame: From surgery start to surgery end
Duration of Hospitalization
Time frame: From the day of surgery to the day of discharge, or 30 days after surgery if the patients is still hospitalized
Readmission
Time frame: From the end of surgery to 30 days after surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38026375Song S, Pei L, Chen H, Zhang Y, Sun C, Yi J, Huang Y. Analysis of hospital and payer costs of care: aggressive warming versus routine warming in abdominal major surgery. Front Public Health. 2023 Nov 2;11:1256254. doi: 10.3389/fpubh.2023.1256254. eCollection 2023.
- Derived from this study: PubMed 35390321Sessler 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.
- Individual participant dataSharing planned: Yes. Investigators are welcome to propose collaborative analyses.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing aggressive warming and routine thermal management in people with Perioperative Care and Surgery--Complications, run by The Cleveland Clinic at 11 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in China, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With a Composite Outcome Consisted of Myocardial Injury After Non-cardiac Surgery (MINS), Non-fatal Cardiac Arrest, and All-cause Mortality (time frame: From the end of surgery to 30 days after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03111875, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2023.