Ignite Creation Date:
2024-05-06 @ 5:29 PM
Last Modification Date:
2024-10-26 @ 2:29 PM
Study NCT ID:
NCT05322395
Status:
RECRUITING
Last Update Posted:
2024-03-05
First Post:
2022-01-04
Brief Title:
Pragmatic Randomised Trial of the ESC 01 Versus 03 Hour Troponin Pathway
Sponsor:
Liverpool University Hospitals NHS Foundation Trust
Organization:
Liverpool University Hospitals NHS Foundation Trust
Study Overview
Official Title:
Safety and Feasibility of Triage and Rapid Discharge of Patients With Chest Pain From Accident and Emergency a Pragmatic Randomised Multicentre Non-inferiority Control Trial of the Accelerated European Society of Cardiology ESC 0-1 Hour Pathway vs Conventional 0-3 Hour Accelerated Diagnostic Protocol
Status:
RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MACROS2
Brief Summary:
The primary objective of this study is to assess the feasibility and impact of implementing the ESC 0-1 hour high sensitive troponin pathway in clinical practice and with specific reference to the 0-3 hour pathway currently in use
The principal outcome measure will be the safety of the 0-1 hour protocol which is less established and has limited data on safety when implemented in clinical practice
The principal outcome measure will be the safety of the 0-1 hour protocol which is less established and has limited data on safety when implemented in clinical practice
Detailed Description:
1 the investigators propose to compare 2 gold standard NICE recommendedESC guideline-backed pathways the accelerated 0-1 hour troponin clinical pathway versus the conventional 0-3-hour pathway in a randomised multicentre controlled study
1 The primary outcome is to compare percentage safe with the emphasis and sample size calculation on safety discharge by 4 hours from presentation by means of the 0-3 hours versus the 0-1-hour with the 0 hour in both pathways incorporating discharge using the limit of detection
2 the investigators propose to use high sensitivity troponin T hs cTnT ROCHE Elecsys assay as this is currently in routine clinical use at the site for this purpose and also perform comparative analyses using a high sensitivity troponin I hs cTnI assay ABBOTT Architect
2 Redundant blood sample will also be used to evaluate point of care testing POCT with additional blood sample taken for POC These samples will be undertaken as part of routine clinical care and will not require additional venepuncture and will only be analysed if consent is gained for tissue use in research population A co-primary endpoint will be single sample rule-out by point of care troponin POCT with a value of 4ngl in those with chest pain onset 3 hours from presentation as assessed in the recent APACE study of triage true POC11 A comparison of this rule-out in terms of effectiveness percentage discharge and safety sensitivity will be made with ROCHE lod 5ngl12 and the optimised rule-out of Abbott architect HSTNI5ngl13
22 Secondary objectives
1 The relative performance of the Abbott Architect high sensitivity troponin I hs TnI Quidels TriageTrue and Siemens Attellica troponin I assay will also be assessed in terms of the primary and secondary endpoints by reference to high sensitivity troponin T hs cTnT with cut-points for Abbott hs-cTn I from the BACC study used for the 0-1-hour pathway14
2 The performance of the novel machine learning algorithm the Myocardial Ischemic Injury Index MI3 Abbott will also be assessed retrospectively with regard to safety and efficacy This sub study using fully anonymized data will be performed in association with coinvestigators from Abbott Diagnostics appendix 1
3 To understand if low levels of Growth Differentiation Factor GDF-15 could expand safe discharge beyond the LOD This will be tested for retrospectively in stored plasma samples
4 To assess if point of care troponin samples at time points at 1 to 3 hours additional samples mirror gold standard high sensitive troponin analysis with respect to diagnosis of acute or chronic myocardial injury andor type 1 or type 2 myocardial infarction
3 Hypothesis That an accelerated 0-1-hour troponin protocol when implemented into clinical practice as a pragmatic RCT will effect safe discharge with greater numbers discharged by 4 hours from presentation compared to the use of the more conventional 0-3 hour troponin protocol
Means to test hypothesis A two-arm parallel group two-centre randomised controlled trial of 0-1-hour high sensitivity troponin T hs cTnT compared to a 0-3-hour pathway as rules for rapid discharge of suspected ACS both incorporating single presentation sample limit of detection LOD high sensitive troponin as a rule for discharge or cut-off selected by manufacturer
The power of the study is on safety rather than percent discharge achieved by 4 hours as this is the primary focus for clinicians and health care institutions By virtue of the earlier sampling the 0-1 hour troponin sampling is likely to allow greater discharges by 4 hours and the sample size for safety easily accommodates this aspect
4 Outcomes 41 Primary endpoint
1 the investigators will compare safe discharge by each strategy ie the ESC 0-1 hour pathway versus 0-3 pathway and the proportion actually discharged by each pathway at 4 hours The exact definition of safety will be percentage of cohort randomised to each pathway safely discharged by 4 hours of presentation to accident and emergency Safety will be judged by type 1 myocardial infarction cardiovascular death by 4 weeks with sensitivity 98 - the study will be powered on safety to establish whether 0-1-hour performance is equivalent to 0-3-hour sampling by means of a non-inferiority analysis- see statistics
Type 1 myocardial infarction is due to acute coronary atherothrombotic myocardial injury with either plaque rupture or erosion and often associated thrombosis A separate analysis will also be undertaken with inclusion of type 2 MI as well as type 1 MI as an endpoint
42 Co-primary endpoint There will be a comparison of the real time performance of point of care troponin POCT assay to that of a sample sent for analysis in the laboratory the current gold standard of central laboratory analysis using HS cTnThe primary interest will be in presentation sample POC rule-out triage true quidel POC 4ngl with CP onset 3 hours compared to LOD or optimised rule-out of ROCHE elecsys assay siemens attelica and Abbott architect There will be a similar comparison made with siemens VTLI troponin I POC assay using FDA approved cut-points for MI rule-out
43 Secondary Endpoints
1 Type 1 myocardial infarction adjudicated with the use of Abbott hs cTnI and cardiovascular death at 4 weeks target for safety negative predictive value NPV 995 and sensitivity 98 co-primary endpoint This analysis will be repeated incorporating both type 1 and 2 MI definition prespecified secondary analysis
2 All cause death type 1 myocardial infarction and urgent or emergency revascularisation This analysis will be repeated incorporating both type 1 and 2 MI definition prespecified secondary analysis
3 Proportion with rule-out or rule-in MI in the 0-1 hour and 0-3 hour
4 Prediction of MI with myocardial ischemic injury index MI3 algorithm9
5 HEART 3 and a modified HEART score for rule-out MI at 30 days15
6 Proportion with repeat presentations to accident and emergency within 30 days
7 Proportion undergoing coronary angiography and coronary revascularisation in 0-1 versus 0-3 hour pathway
8 Performance of point of care troponin samples at time points at 1 to 3 hours additional samples to 0 hour with respect to diagnosis of acute or chronic myocardial injury andor type 1 myocardial infarction
9 Rule out of MI with GDF-15 Growth Differentiation Factor 15
Cardiovascular deaths include deaths that result from an myocardial infarctions MI sudden cardiac death death due to heart failure HF death due to stroke death due to cardiovascular procedures death due to cardiovascular haemorrhage and death due to other cardiovascular causes and deaths that do not have a clear non- cardiovascular cause
1 The primary outcome is to compare percentage safe with the emphasis and sample size calculation on safety discharge by 4 hours from presentation by means of the 0-3 hours versus the 0-1-hour with the 0 hour in both pathways incorporating discharge using the limit of detection
2 the investigators propose to use high sensitivity troponin T hs cTnT ROCHE Elecsys assay as this is currently in routine clinical use at the site for this purpose and also perform comparative analyses using a high sensitivity troponin I hs cTnI assay ABBOTT Architect
2 Redundant blood sample will also be used to evaluate point of care testing POCT with additional blood sample taken for POC These samples will be undertaken as part of routine clinical care and will not require additional venepuncture and will only be analysed if consent is gained for tissue use in research population A co-primary endpoint will be single sample rule-out by point of care troponin POCT with a value of 4ngl in those with chest pain onset 3 hours from presentation as assessed in the recent APACE study of triage true POC11 A comparison of this rule-out in terms of effectiveness percentage discharge and safety sensitivity will be made with ROCHE lod 5ngl12 and the optimised rule-out of Abbott architect HSTNI5ngl13
22 Secondary objectives
1 The relative performance of the Abbott Architect high sensitivity troponin I hs TnI Quidels TriageTrue and Siemens Attellica troponin I assay will also be assessed in terms of the primary and secondary endpoints by reference to high sensitivity troponin T hs cTnT with cut-points for Abbott hs-cTn I from the BACC study used for the 0-1-hour pathway14
2 The performance of the novel machine learning algorithm the Myocardial Ischemic Injury Index MI3 Abbott will also be assessed retrospectively with regard to safety and efficacy This sub study using fully anonymized data will be performed in association with coinvestigators from Abbott Diagnostics appendix 1
3 To understand if low levels of Growth Differentiation Factor GDF-15 could expand safe discharge beyond the LOD This will be tested for retrospectively in stored plasma samples
4 To assess if point of care troponin samples at time points at 1 to 3 hours additional samples mirror gold standard high sensitive troponin analysis with respect to diagnosis of acute or chronic myocardial injury andor type 1 or type 2 myocardial infarction
3 Hypothesis That an accelerated 0-1-hour troponin protocol when implemented into clinical practice as a pragmatic RCT will effect safe discharge with greater numbers discharged by 4 hours from presentation compared to the use of the more conventional 0-3 hour troponin protocol
Means to test hypothesis A two-arm parallel group two-centre randomised controlled trial of 0-1-hour high sensitivity troponin T hs cTnT compared to a 0-3-hour pathway as rules for rapid discharge of suspected ACS both incorporating single presentation sample limit of detection LOD high sensitive troponin as a rule for discharge or cut-off selected by manufacturer
The power of the study is on safety rather than percent discharge achieved by 4 hours as this is the primary focus for clinicians and health care institutions By virtue of the earlier sampling the 0-1 hour troponin sampling is likely to allow greater discharges by 4 hours and the sample size for safety easily accommodates this aspect
4 Outcomes 41 Primary endpoint
1 the investigators will compare safe discharge by each strategy ie the ESC 0-1 hour pathway versus 0-3 pathway and the proportion actually discharged by each pathway at 4 hours The exact definition of safety will be percentage of cohort randomised to each pathway safely discharged by 4 hours of presentation to accident and emergency Safety will be judged by type 1 myocardial infarction cardiovascular death by 4 weeks with sensitivity 98 - the study will be powered on safety to establish whether 0-1-hour performance is equivalent to 0-3-hour sampling by means of a non-inferiority analysis- see statistics
Type 1 myocardial infarction is due to acute coronary atherothrombotic myocardial injury with either plaque rupture or erosion and often associated thrombosis A separate analysis will also be undertaken with inclusion of type 2 MI as well as type 1 MI as an endpoint
42 Co-primary endpoint There will be a comparison of the real time performance of point of care troponin POCT assay to that of a sample sent for analysis in the laboratory the current gold standard of central laboratory analysis using HS cTnThe primary interest will be in presentation sample POC rule-out triage true quidel POC 4ngl with CP onset 3 hours compared to LOD or optimised rule-out of ROCHE elecsys assay siemens attelica and Abbott architect There will be a similar comparison made with siemens VTLI troponin I POC assay using FDA approved cut-points for MI rule-out
43 Secondary Endpoints
1 Type 1 myocardial infarction adjudicated with the use of Abbott hs cTnI and cardiovascular death at 4 weeks target for safety negative predictive value NPV 995 and sensitivity 98 co-primary endpoint This analysis will be repeated incorporating both type 1 and 2 MI definition prespecified secondary analysis
2 All cause death type 1 myocardial infarction and urgent or emergency revascularisation This analysis will be repeated incorporating both type 1 and 2 MI definition prespecified secondary analysis
3 Proportion with rule-out or rule-in MI in the 0-1 hour and 0-3 hour
4 Prediction of MI with myocardial ischemic injury index MI3 algorithm9
5 HEART 3 and a modified HEART score for rule-out MI at 30 days15
6 Proportion with repeat presentations to accident and emergency within 30 days
7 Proportion undergoing coronary angiography and coronary revascularisation in 0-1 versus 0-3 hour pathway
8 Performance of point of care troponin samples at time points at 1 to 3 hours additional samples to 0 hour with respect to diagnosis of acute or chronic myocardial injury andor type 1 myocardial infarction
9 Rule out of MI with GDF-15 Growth Differentiation Factor 15
Cardiovascular deaths include deaths that result from an myocardial infarctions MI sudden cardiac death death due to heart failure HF death due to stroke death due to cardiovascular procedures death due to cardiovascular haemorrhage and death due to other cardiovascular causes and deaths that do not have a clear non- cardiovascular cause
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None