Very Early Versus Delayed Angiography +/- Intervention on Outcomes in Patients With NSTEMI

Cardiovascular; Attack Clinical Trial

— RapidNSTEMI  

Official title:

A Randomised Controlled Trial of Very Early Angiography +/- Intervention Versus Standard of Care on Outcomes in Patients With Non ST-elevation Myocardial Infarction

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03707314
• Other study ID #: EDGE 89678
• Status: Terminated
• Phase: N/A
• Start date: November 6, 2018
• Est. completion date: October 28, 2021

Study information

• Verified date: November 2022
• Source: University Hospitals, Leicester
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Prospective, open, multicentre, randomised controlled trial in patients with higher risk non-ST elevation myocardial infarction acute coronary syndrome

Description:

Background: Clinical event rates in Non ST elevation myocardial infarction acute coronary syndrome (N-STEMI ACS) patients remain high, with one year MACE rates as high as 20%. While there may be early mortality differences between N-STEMI and STEMI, outcomes beyond one year become very similar. N-STEMI ACS patients therefore rightly remain the focus of a number of research directives. The objective of the RAPID-NSTEMI trial is to determine if clinical outcomes can be improved by very early intervention in a pre-determined higher risk N-STEMI ACS population. Published data has shown that inpatient Percutaneous Coronary Intervention (PCI) in N-STEMI ACS patients reduces subsequent clinical events. This had led to guidelines supporting its use in clinical practice. However, there is much less certainty regarding the timing of the PCI and, in particular, whether this should be a strategy used early to optimize outcomes. Thus, while evidence based guidelines (NICE and European) provide general time parameters for PCI, immediate angiography with a view to intervention in higher risk patients has never been robustly tested in any adequately powered, prospective randomised trial with clinical end points. The RAPID-NSTEMI trial sets out to test the benefits, or otherwise, of a strategy of immediate angiography with follow-on revascularisation in higher risk N-STEMI ACS patients.

Hypothesis: Very early angiography +/- PCI improves clinical outcomes in higher risk NSTEMI patients when compared to standard invasive management.

Methods: In order to identify higher risk patients as soon as possible after presentation, a high sensitivity troponin (Hs-Troponin-T or Hs-Troponin-I) will be taken, allowing calculation of a GRACE 2.0 score (GS 2.0) early after admission. The GS 2.0 will be determined in sufficient time to be able to test an early intervention strategy arm. Patients with GS 2.0 of ≥118 alone, or ≥90 with additional high risk features will be randomised in a 1:1 fashion to one of two groups:

Group A: immediate angiography with follow-on revascularisation if required Group B: standard care - pharmacological treatment until angiography with follow on revascularisation if required (preferably within 72 hours as per current guidelines).

The primary outcome for the main study will be a 12-month of all-cause mortality, new myocardial infraction and hospital admission with heart failure.

Power calculations indicate that 2314 patients are required to show MACE superiority for early intervention in such higher risk N-STEMI ACS patients.

Analyses will be primarily according to "intention to treat", with a secondary analysis according to trial treatment received (comparing those who actually received follow-on revascularisation at the two different trial time points). There will be a cost effectiveness analysis.

Mechanistic sub-studies in the two groups will be undertaken.

1. Cardiac magnetic resonance imaging substudy to assess differences in infarct size, oedema, microvascular obstruction and left ventricular ejection fraction between the two arms.

2. Novel biomarkers substudy that will be funded separately after appropriate funding applications

Expected value of results: The investigators have designed a superiority trial to anticipate that outcomes will be improved in higher risk patients revascularised very early after presentation with N-STEMI. Irrespective of outcome, this trial should determine whether there is a need for a change in current patient management of a common condition and, in particular, if all N-STEMI patients should be admitted to a PCI-capable hospital to allow for very early intervention. The results will inform national and international guidelines. The planned cost effectiveness analysis will become particularly important if clinical outcomes are no different between groups since length of stay should be different.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 425
• Est. completion date: October 28, 2021
• Est. primary completion date: October 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• 18 years of age and over

• Patients presenting to hospitals with a clinical diagnosis of non-ST elevation myocardial infarction comprising:

• Ischaemic symptoms (as defined in Appendix III of protocol)

• Elevated high sensitivity Troponin T or I (above the normal range for individual hospitals)

• GRACE-2.0 score (www.gracescore.org) of either:

• =118 (corresponding to 6-month death >6%) OR

• =90 but <118 (corresponding to 6-month death >3% but <6%)

• If GRACE 2.0 score =90 or <118 must have at least one additional high risk feature:

• Anterior location of ECG changes (leads V2 - V5)

• ST-segment depression in 2 contiguous leads (any territory) of 0.15mV/ 1.5mm.

• Diabetes Mellitus on medication

• High-sensitivity Troponin I or T 3 x ULN

• Onset of ischaemic symptoms at any time prior to admission but most recent episode within 12 hours to admission

• Intention to perform angiography and, if indicated, follow-on revascularisation

• Provision of assent or written consent

• Randomisation must be performed within 6 hours of admission

Exclusion Criteria

• ST elevation myocardial infarction

• Evident type 2 myocardial infarction (e.g. anaemia)

• Evidence of previous known cardiomyopathy

• Cardiogenic Shock

• Known severe valvular heart disease

• Need for urgent PCI according to ESC Guidelines (haemodynamic instability, VT, VF, recurrent or persistent pain)

• Any contraindication to PCI

• Current participation in another intervention trial

Related Conditions & MeSH terms

• Cardiovascular; Attack

Intervention

Procedure:
• Angiography with follow-on revascularisation if indicated
Angiography with follow-on revascularisation (if indicated)

Locations

Country	Name	City	State
United Kingdom	Glenfield Hospital, University Hospitals of Leicester NHS Trust	Leicester

Sponsors (4)

Lead Sponsor	Collaborator
University Hospitals, Leicester	British Heart Foundation, University of East Anglia, University of Leicester

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major adverse cardiovascular events	Incidence of the composite of all-cause mortality, new myocardial infarction and admission for heart failure within 12 months following randomisation	12 months
Secondary	All-cause mortality	Incidence of all-cause mortality	12 months
Secondary	New myocardial infarction	Incidence of new myocardial infarction	12 months
Secondary	Heart failure	Incidence of admission for heart failure	12 months
Secondary	Cardiovascular mortality	Incidence of cardiovascular mortality	12 months
Secondary	Length of in-patient stay	Length of in-patient stay (defined as randomisation to first discharge) in days	Through study completion, 3 years
Secondary	All-cause mortality prior to planned coronary angiography	Incidence of all-cause mortality prior to planned coronary angiography following index admission with NSTEMI	During index admission
Secondary	New myocardial infarction prior to planned coronary angiography	Incidence of new myocardial infarction prior to planned coronary angiography following index admission with NSTEMI	During index admission
Secondary	Major bleeding prior to planned coronary angiography	Incidence of major bleeding (classified as BARC 3-5) prior to planned coronary angiography following index admission with NSTEMI	During index admission
Secondary	Admission for ischaemia-driven revascularisation	Incidence of admission for ischaemia-driven revascularisation	12 months
Secondary	Admission for any cause	Incidence of admission for any cause	12 months
Secondary	Quality of life measured using Seattle Angina Questionnaire	Quality of life measured using Seattle Angina Questionnaire at 24 hours post procedure, 1 month, 6 months and 12 months	12 months
Secondary	Quality of life measured using EuroQoL-5D-5L questionnaire	Quality of life measured using the EuroQoL-5D-5L questionnaire at 24 hours post procedure, 1 month, 6 months and 12 months	12 months
Secondary	BARC 3-5 bleeding	Incidence of Bleeding Academic Research Consortium (BARC) 3-5 classified bleeding as in-patient, and up to 12 months	12 months
Secondary	Stroke	Incidence of stroke	12 months
Secondary	Cost effectiveness	Cost effectiveness of immediate PCI versus standard care	12 months
Secondary	Left ventricular ejection fraction on cardiac MRI	Left ventricular ejection fraction on cardiac MRI	7 days (+/-3 days)
Secondary	Infarct size on cardiac MRI	Infarct size on cardiac MRI	7 days (+/-3 days)
Secondary	Proportion of patients needing emergency/urgent revascularisation	Proportion of patients needing emergency/urgent revascularisation (in group B)	3-4 days (standard of care timing angiography will vary between recruiting centres)
Secondary	Total access site complications	Incidence of total VARC-2 classified access site complications as in-patient, and up to 12 months	12 months
Secondary	Major access site complications	Incidence of major VARC-2 classified access site complications as in-patient, and up to 12 months	12 months
Secondary	Sensitivity and specificity of novel biomarkers for predicting need for revascularisation	Sensitivity and specificity of novel biomarkers in predicting which patients do or do not require PCI following diagnostic angiography	3-4 days (standard of care timing angiography will vary between recruiting centres)