Myocardial IschemiaPMINCT03438448
Perioperative Myocardial Ischemia: Troponin Monitoring,Cost-effectiveness, Insights Into Pathophysiology
An observational study of Myocardial Ischemia and Myocardial Injury, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 1 site in Spain.
Trial summary
Background: Despite preoperative screening, technical improvements and increased patient monitoring, perioperative myocardial infarction (PMI) remains the first cause of morbidity and mortality within 30 days after surgery. Read more about this study
- Who is it for?
- Ages 45 to 98 years
- Conditions the study is for
- Myocardial Ischemia, Myocardial Injury, Morality
- What is being tested?
- High sensitive Troponin T monitoring
- How many people
- 1,510 participants
- Where
- 1 siteSpain
- Study dates
- 11 Jul 2016to 6 Mar 2020
- How long will I take part?
- 1 Year
- Phase
- Observational
- Are there results?
- None posted in the registry
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 to 98 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adults ≥ 65 years or < 65 years with documented cardiovascular disease (history of coronary artery disease, history of congestive heart disease, history of stroke, history of peripheral vascular disease) undergoing a major non-cardiac surgery can considered for eligibility. Eligible Patients will be approached for informed consent after surgery and before hospital discharge.
Who may be able to join
- Age ≥ 65 years.
- Age < 65 years and documented cardiovascular disease (history of coronary artery disease, history of congestive heart disease, history of stroke, history of peripheral vascular disease).
- Renal insufficiency (GF <60ml/min).
Who cannot join
- Patients undergoing non cardiac surgery that do not require an overnight hospital admission or that only receive infiltrative (i.e., local) or topical anesthesia.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Perioperative Myocardial Ischemia: Implementation of Troponin Monitoring, Economic Analysis and Further Insights Into Pathophysiology
Background: Despite preoperative screening, technical improvements and increased patient monitoring, perioperative myocardial infarction (PMI) remains the first cause of morbidity and mortality within 30 days after surgery. Moreover, the available evidence indicates worrying rise of risk in postoperative patients with only elevated troponins reflecting cardiac injury, but without a conventional clinical diagnosis of myocardial infarction according to current definition. Worldwide, annually approximately 300 million adults undergo major non cardiac surgery and 10 million of them are estimated to suffer a myocardial injury after non-cardiac surgery (MINS), defined as a prognostically relevant increase of a troponin T peak of 0.03 ng/ml or greater. Many of the patients with MINS does not fulfill the universal definition of myocardial infarction, rarely experience ischemic symptoms and their prognosis is very poor (1 out of 10 die at 30 days).Troponin levels needed to be monitored in order to MINS diagnose and high sensitive cardiac troponin T assays are currently the most frequently used.
Methods: Patients with high cardiovascular risk undergoing major non-cardiac surgery will be selected from the daily surgical program during a two years period Three determinations of hs-cTnT for each patient will be obtained. The proportion of patients with MINS and pre- and post-operative thresholds of hs-cTnT that would be prognostically relevant will be determined. The cost-effectiveness analysis of hs-cTnT monitoring compared with usual care will be undertaken. Finally using computed tomography angiography (CTA) and cardiac magnetic resonance imaging (MRI) pathophysiology of MINS will be determined, whether is due to plaque rupture, supply-demand mismatch, non-ischemic cardiac cause or non-cardiac cause.
Discussion: The study will evaluate the feasibility and impact of implementing the hs-cTnT monitoring program in the Hospital de la Santa Creu i Sant Pau of Barcelona, as well as its cost-effectiveness. Moreover, this is the first study which will determine pre and postoperative thresholds of hs-cTnT and with minimally invasive diagnostic tools will evaluate potential mechanisms involved in perioperative ischemic events.
Read the detailed description
The study consists of four sub studies
- Troponin monitoring implementation - Sub study A
- Preoperative and postoperative hs-cTnT threshold - Sub study B
- Economic analysis - Sub study C
- Advanced cardiac imaging case-control study - Sub study D
Study A:To implement and evaluate a Troponin T monitoring program in patients with high cardiovascular risk undergoing major non-cardiac surgery, the investigators will include prospectively patients with one or more of the following inclusion criteria (intervention cohort). Age, sex, type of surgery, revised cardiac risk index, history of coronary artery disease, history of cardiac arrest, history of congestive heart failure, history of peripheral vascular disease, history of stroke, history of a transient ischemic attack, chronic renal failure, history of deep venous thrombosis or pulmonary embolism, diabetes, hypertension, current atrial fibrillation, chronic obstructive pulmonary disease, type of treatment (statins and antithrombotic treatments) will be collected.
The investigators will obtain three determinations of Roche high-sensitive troponin T (99th percentile (14 ng/L) for each patient: preoperative (during the preoperative visit or just before surgery), 48h, and 72h after surgery. If a rise and/or fall of hs-cTnT with at least one value above the 99th percentile upper reference is detected, a clinical evaluation and a 12-lead ECG will be performed. If no ECG changes, ischemic symptoms, or pulmonary edema to fulfill the diagnostic for PMI the patients will undergo an echocardiographic study.
Study B: All patients included in study A (see above) will included. The investigators will measure high sensitivity cardiac troponin T using a Roche Elecsys 2010 analyzer (limit of detection 5.0 ng/L, 99th percentile 14 ng/L, a 10% coefficient of variation at 13 ng/L) at three predefined time points: preoperatively (during the preoperative visit or just before surgery), at 48h and 72h after surgery. The main outcome will be 30 day and 1 year mortality.
Study C: To analyze the cost-effectiveness of a hs-cTnT screening program for the detection of PMI compared to the current practice (no screening). The investigators will structure a model as a decision tree analysis. Two alternatives will be considered: the application of screening program for detection of PMI versus current practice, based on the application of standard treatments in the presence of ischemic symptoms.
Study D: All the patients from hs-cTnT screening study mentioned above (A) who fulfill MINS criteria will be recruited in this study. After obtaining written informed consent, all variables included risk factors, comorbidities, medical treatment and perioperative data will be recollected by researchers. Within the postoperative hospitalization period, CTA and MRI studies will be performed in all cases.
Two groups of patients will be distinguished :
- MINS/PMI group: composed by patients with hs-cTnT value higher than 50% of preoperative level, without symptoms, without ECG changes related to ischemia, neither new wall abnormalities in the postoperative echocardiogram. Moreover PMI group will be composed by patients with perioperative myocardial infarction according the current definition.
- Control group: composed by patients without PMI or MINS.
After a matching analyses for the principal confounding factors (age, sex, Lee index, type of surgery), one control for each case will be selected to complete CTA and MRI examinations.
In MRIs the investigators will do an analysis of global and segmental contractility baseline perfusion, a pharmacological stress with adenosine, and an assessment of necrosis and myocardial viability by studying late gadolinium enhancement contrast. In CTAs the investigators will evaluate plaque morphology, plaque size and composition, stenosis and remodeling index.
Given these findings, and with the information provided by clinical history and eventual ECG changes, the investigators will classify MINS patients as (1) due to plaque rupture, (2) supply-demand mismatch, (3) non-ischemic cardiac cause, or (4) non-cardiac cause.
- Conditions
- Myocardial Ischemia, Myocardial Injury, Morality
- Being tested
- High sensitive Troponin T monitoring
- Keywords
- Ultrasensitive Troponin T, MINS, Cost-effectiveness, Myocardial Ischemia
- Medical subject headings
- Myocardial Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High sensitive Troponin T monitoringOther
Three determinations of Roche high-sensitive troponin T (99th percentile (14 ng/L) for each patient: preoperative (during the preoperative visit or just before surgery), 48h, and 72h after surgery. If a rise and/or fall of hs-cTnT with at least one value above the 99th percentile upper reference is detected, a clinical evaluation and a 12-lead ECG will be performed. If no ECG changes, ischemic symptoms, or pulmonary edema to fulfill the diagnostic for PMI the patients will undergo an echocardiographic study.
What is being measured
The primary outcome is the main question the study is designed to answer.
All cause mortality
Occurence of all cause mortality
Measured: 1 month and 1 year after surgery
Secondary outcomes (2)
Major adverse cardiac events (MACE)
Occurrence of MACE: myocardial infarction, unstable angina, congestive heart failure, new atrial fibrillation, stroke or pulmonary embolism
Measured: 1 month and 1 year after surgery
Medication modifications
Starting new medication or modifying dose
Measured: 1 month and 1 year after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2018
- Study start11 Jul 2016
- Primary completion6 Mar 2019
- Study completion6 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Myocardial IschemiaStudies of the same condition, open and under way.
- More trials run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,510 participants (actual)
- Target duration
- 1 Year
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pablo Alonso-Coello, MD, PhD, Principal investigator, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03438448
- Sponsor's protocol ID
- IIBSP-IMP-2015-95
- Acronym
- PMI
- Status last verified
- Jan 2022
- First submitted
- 13 Feb 2018
- Last updated
- 12 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Alvarez-Garcia J, Popova E, Vives-Borras M, de Nadal M, Ordonez-Llanos J, Rivas-Lasarte M, Moustafa AH, Sole-Gonzalez E, Paniagua-Iglesias P, Garcia-Moll X, Vilades-Medel D, Leta-Petracca R, Oristrell G, Zamora J, Ferreira-Gonzalez I, Alonso-Coello P, Carreras-Costa F. Myocardial injury after major non-cardiac surgery evaluated with advanced cardiac imaging: a pilot study. BMC Cardiovasc Disord. 2023 Feb 10;23(1):78. doi: 10.1186/s12872-023-03065-6.
PubMed 36765313Popova E, Alonso-Coello P, Alvarez-Garcia J, Paniagua-Iglesias P, Rue-Monne M, Vives-Borras M, Font-Gual A, Gich-Saladich I, Martinez-Bru C, Ordonez-Llanos J, Carles-Lavila M. Cost-effectiveness of a high-sensitivity cardiac troponin T systematic screening strategy compared with usual care to identify patients with peri-operative myocardial injury after major noncardiac surgery. Eur J Anaesthesiol. 2023 Mar 1;40(3):179-189. doi: 10.1097/EJA.0000000000001793. Epub 2023 Jan 11.
PubMed 36722187
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Perioperative Myocardial Ischemia: Implementation of Troponin Monitoring, Economic Analysis and Further Insights Into Pathophysiology
- ClinicalTrials.gov ID
- NCT03438448
- Acronym / sponsor ID
- PMI / IIBSP-IMP-2015-95
- Conditions
- Myocardial Ischemia, Myocardial Injury, Morality
- Keywords
- Ultrasensitive Troponin T, MINS, Cost-effectiveness, Myocardial Ischemia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,510 participants (actual)
- Lead sponsor
- Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauUniversity, hospital or other
- Study start
- 11 Jul 2016 (actual)
- Primary completion
- 6 Mar 2019 (actual)
- Study completion
- 6 Mar 2020 (actual)
- First posted
- 19 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background: Despite preoperative screening, technical improvements and increased patient monitoring, perioperative myocardial infarction (PMI) remains the first cause of morbidity and mortality within 30 days after surgery. Moreover, the available evidence indicates worrying rise of risk in postoperative patients with only elevated troponins reflecting cardiac injury, but without a conventional clinical diagnosis of myocardial infarction according to current definition. Worldwide, annually approximately 300 million adults undergo major non cardiac surgery and 10 million of them are estimated to suffer a myocardial injury after non-cardiac surgery (MINS), defined as a prognostically relevant increase of a troponin T peak of 0.03 ng/ml or greater. Many of the patients with MINS does not fulfill the universal definition of myocardial infarction, rarely experience ischemic symptoms and their prognosis is very poor (1 out of 10 die at 30 days).Troponin levels needed to be monitored in order to MINS diagnose and high sensitive cardiac troponin T assays are currently the most frequently used.
Methods: Patients with high cardiovascular risk undergoing major non-cardiac surgery will be selected from the daily surgical program during a two years period Three determinations of hs-cTnT for each patient will be obtained. The proportion of patients with MINS and pre- and post-operative thresholds of hs-cTnT that would be prognostically relevant will be determined. The cost-effectiveness analysis of hs-cTnT monitoring compared with usual care will be undertaken. Finally using computed tomography angiography (CTA) and cardiac magnetic resonance imaging (MRI) pathophysiology of MINS will be determined, whether is due to plaque rupture, supply-demand mismatch, non-ischemic cardiac cause or non-cardiac cause.
Discussion: The study will evaluate the feasibility and impact of implementing the hs-cTnT monitoring program in the Hospital de la Santa Creu i Sant Pau of Barcelona, as well as its cost-effectiveness. Moreover, this is the first study which will determine pre and postoperative thresholds of hs-cTnT and with minimally invasive diagnostic tools will evaluate potential mechanisms involved in perioperative ischemic events.
Detailed description
The study consists of four sub studies
- Troponin monitoring implementation - Sub study A
- Preoperative and postoperative hs-cTnT threshold - Sub study B
- Economic analysis - Sub study C
- Advanced cardiac imaging case-control study - Sub study D
Study A:To implement and evaluate a Troponin T monitoring program in patients with high cardiovascular risk undergoing major non-cardiac surgery, the investigators will include prospectively patients with one or more of the following inclusion criteria (intervention cohort). Age, sex, type of surgery, revised cardiac risk index, history of coronary artery disease, history of cardiac arrest, history of congestive heart failure, history of peripheral vascular disease, history of stroke, history of a transient ischemic attack, chronic renal failure, history of deep venous thrombosis or pulmonary embolism, diabetes, hypertension, current atrial fibrillation, chronic obstructive pulmonary disease, type of treatment (statins and antithrombotic treatments) will be collected.
The investigators will obtain three determinations of Roche high-sensitive troponin T (99th percentile (14 ng/L) for each patient: preoperative (during the preoperative visit or just before surgery), 48h, and 72h after surgery. If a rise and/or fall of hs-cTnT with at least one value above the 99th percentile upper reference is detected, a clinical evaluation and a 12-lead ECG will be performed. If no ECG changes, ischemic symptoms, or pulmonary edema to fulfill the diagnostic for PMI the patients will undergo an echocardiographic study.
Study B: All patients included in study A (see above) will included. The investigators will measure high sensitivity cardiac troponin T using a Roche Elecsys 2010 analyzer (limit of detection 5.0 ng/L, 99th percentile 14 ng/L, a 10% coefficient of variation at 13 ng/L) at three predefined time points: preoperatively (during the preoperative visit or just before surgery), at 48h and 72h after surgery. The main outcome will be 30 day and 1 year mortality.
Study C: To analyze the cost-effectiveness of a hs-cTnT screening program for the detection of PMI compared to the current practice (no screening). The investigators will structure a model as a decision tree analysis. Two alternatives will be considered: the application of screening program for detection of PMI versus current practice, based on the application of standard treatments in the presence of ischemic symptoms.
Study D: All the patients from hs-cTnT screening study mentioned above (A) who fulfill MINS criteria will be recruited in this study. After obtaining written informed consent, all variables included risk factors, comorbidities, medical treatment and perioperative data will be recollected by researchers. Within the postoperative hospitalization period, CTA and MRI studies will be performed in all cases.
Two groups of patients will be distinguished :
- MINS/PMI group: composed by patients with hs-cTnT value higher than 50% of preoperative level, without symptoms, without ECG changes related to ischemia, neither new wall abnormalities in the postoperative echocardiogram. Moreover PMI group will be composed by patients with perioperative myocardial infarction according the current definition.
- Control group: composed by patients without PMI or MINS.
After a matching analyses for the principal confounding factors (age, sex, Lee index, type of surgery), one control for each case will be selected to complete CTA and MRI examinations.
In MRIs the investigators will do an analysis of global and segmental contractility baseline perfusion, a pharmacological stress with adenosine, and an assessment of necrosis and myocardial viability by studying late gadolinium enhancement contrast. In CTAs the investigators will evaluate plaque morphology, plaque size and composition, stenosis and remodeling index.
Given these findings, and with the information provided by clinical history and eventual ECG changes, the investigators will classify MINS patients as (1) due to plaque rupture, (2) supply-demand mismatch, (3) non-ischemic cardiac cause, or (4) non-cardiac cause.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Year
Who may qualify
- Ages
- 45 to 98 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults ≥ 65 years or < 65 years with documented cardiovascular disease (history of coronary artery disease, history of congestive heart disease, history of stroke, history of peripheral vascular disease) undergoing a major non-cardiac surgery can considered for eligibility. Eligible Patients will be approached for informed consent after surgery and before hospital discharge.
Key inclusion criteria (3 listed)
- Age ≥ 65 years.
- Age < 65 years and documented cardiovascular disease (history of coronary artery disease, history of congestive heart disease, history of stroke, history of peripheral vascular disease).
- Renal insufficiency (GF <60ml/min).
Key exclusion criteria (1 listed)
- Patients undergoing non cardiac surgery that do not require an overnight hospital admission or that only receive infiltrative (i.e., local) or topical anesthesia.
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 |
|---|---|---|
| High sensitive Troponin T monitoringThree determinations of Roche high-sensitive troponin T (99th percentile (14 ng/L) for each patient: preoperative (during the preoperative visit or just before surgery), 48h, and 72h after surgery. If a rise and/or fall of hs-cTnT with at least one value above the 99th percentile upper reference is detected, a clinical evaluation and a 12-lead ECG will be performed. If no ECG changes, ischemic symptoms, or pulmonary edema to fulfill the diagnostic for PMI the patients will undergo an echocardiographic study. | Other | – |
Primary outcome
All cause mortality
Time frame: 1 month and 1 year after surgery
Occurence of all cause mortality
2 secondary outcomes
Major adverse cardiac events (MACE)
Time frame: 1 month and 1 year after surgery
Medication modifications
Time frame: 1 month and 1 year after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2022.
- Derived from this study: PubMed 36765313Alvarez-Garcia J, Popova E, Vives-Borras M, de Nadal M, Ordonez-Llanos J, Rivas-Lasarte M, Moustafa AH, Sole-Gonzalez E, Paniagua-Iglesias P, Garcia-Moll X, Vilades-Medel D, Leta-Petracca R, Oristrell G, Zamora J, Ferreira-Gonzalez I, Alonso-Coello P, Carreras-Costa F. Myocardial injury after major non-cardiac surgery evaluated with advanced cardiac imaging: a pilot study. BMC Cardiovasc Disord. 2023 Feb 10;23(1):78. doi: 10.1186/s12872-023-03065-6.
- Derived from this study: PubMed 36722187Popova E, Alonso-Coello P, Alvarez-Garcia J, Paniagua-Iglesias P, Rue-Monne M, Vives-Borras M, Font-Gual A, Gich-Saladich I, Martinez-Bru C, Ordonez-Llanos J, Carles-Lavila M. Cost-effectiveness of a high-sensitivity cardiac troponin T systematic screening strategy compared with usual care to identify patients with peri-operative myocardial injury after major noncardiac surgery. Eur J Anaesthesiol. 2023 Mar 1;40(3):179-189. doi: 10.1097/EJA.0000000000001793. Epub 2023 Jan 11.
- Individual participant dataSharing planned: Undecided
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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.
Pablo Alonso-Coello, MD, PhD principal investigator
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Myocardial Ischemia and Myocardial Injury, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 1 site in Spain.
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 3 inclusion and 1 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 12 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
All cause mortality (time frame: 1 month and 1 year 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 NCT03438448, 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 12 Jan 2022.