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

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

Sponsors

Lead Sponsor: University Hospitals, Leicester

Collaborator: British Heart Foundation
University of East Anglia
University of Leicester

Source University Hospitals, Leicester
Brief Summary

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

Detailed 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.

Overall Status Recruiting
Start Date November 6, 2018
Completion Date September 30, 2031
Primary Completion Date September 30, 2021
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Major adverse cardiovascular events 12 months
Secondary Outcome
Measure Time Frame
All-cause mortality 12 months
New myocardial infarction 12 months
Heart failure 12 months
Cardiovascular mortality 12 months
Length of in-patient stay Through study completion, 3 years
All-cause mortality prior to planned coronary angiography During index admission
New myocardial infarction prior to planned coronary angiography During index admission
Major bleeding prior to planned coronary angiography During index admission
Admission for ischaemia-driven revascularisation 12 months
Admission for any cause 12 months
Quality of life measured using Seattle Angina Questionnaire 12 months
Quality of life measured using EuroQoL-5D-5L questionnaire 12 months
BARC 3-5 bleeding 12 months
Stroke 12 months
Cost effectiveness 12 months
Left ventricular ejection fraction on cardiac MRI 7 days (+/-3 days)
Infarct size on cardiac MRI 7 days (+/-3 days)
Proportion of patients needing emergency/urgent revascularisation 3-4 days (standard of care timing angiography will vary between recruiting centres)
Total access site complications 12 months
Major access site complications 12 months
Sensitivity and specificity of novel biomarkers for predicting need for revascularisation 3-4 days (standard of care timing angiography will vary between recruiting centres)
Enrollment 2314
Condition
Intervention

Intervention Type: Procedure

Intervention Name: Angiography with follow-on revascularisation if indicated

Description: Angiography with follow-on revascularisation (if indicated)

Eligibility

Criteria:

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Tony Gershlick Study Chair University Hospitals, Leicester
Overall Contact

Last Name: Nafisa Boota

Phone: 0116 229 7298

Phone Ext.: 7298

Email: [email protected]

Location
Facility: Status: Contact: Glenfield Hospital, University Hospitals of Leicester NHS Trust Andrew Ladwiniec, MA MD MRCP
Location Countries

United Kingdom

Verification Date

January 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Number Of Arms 2
Arm Group

Label: Group A: Immediate angiography

Type: Other

Description: Immediate angiography with follow-on revascularisation if indicated

Label: Group B: Standard of care angiography

Type: Other

Description: Standard of care angiography with follow-on revascularisation if indicated (within 3-4 days, but will vary depending on recruiting centre)

Acronym RapidNSTEMI
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Intervention Model Description: Multi-centre parallel design

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov