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

November 8, 2022 updated by: University Hospitals, Leicester

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
425

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Leicester, United Kingdom
        • Glenfield Hospital, University Hospitals of Leicester NHS Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
OTHER: Group A: Immediate angiography
Immediate angiography with follow-on revascularisation if indicated
Procedure: Angiography with follow-on revascularisation if indicated
Angiography with follow-on revascularisation (if indicated)
OTHER: Group B: Standard of care angiography
Standard of care angiography with follow-on revascularisation if indicated (within 3-4 days, but will vary depending on recruiting centre)
Procedure: Angiography with follow-on revascularisation if indicated
Angiography with follow-on revascularisation (if indicated)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Major adverse cardiovascular events
Time Frame: 12 months
Incidence of the composite of all-cause mortality, new myocardial infarction and admission for heart failure within 12 months following randomisation
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
All-cause mortality
Time Frame: 12 months
Incidence of all-cause mortality
12 months
New myocardial infarction
Time Frame: 12 months
Incidence of new myocardial infarction
12 months
Heart failure
Time Frame: 12 months
Incidence of admission for heart failure
12 months
Cardiovascular mortality
Time Frame: 12 months
Incidence of cardiovascular mortality
12 months
Length of in-patient stay
Time Frame: Through study completion, 3 years
Length of in-patient stay (defined as randomisation to first discharge) in days
Through study completion, 3 years
All-cause mortality prior to planned coronary angiography
Time Frame: During index admission
Incidence of all-cause mortality prior to planned coronary angiography following index admission with NSTEMI
During index admission
New myocardial infarction prior to planned coronary angiography
Time Frame: During index admission
Incidence of new myocardial infarction prior to planned coronary angiography following index admission with NSTEMI
During index admission
Major bleeding prior to planned coronary angiography
Time Frame: During index admission
Incidence of major bleeding (classified as BARC 3-5) prior to planned coronary angiography following index admission with NSTEMI
During index admission
Admission for ischaemia-driven revascularisation
Time Frame: 12 months
Incidence of admission for ischaemia-driven revascularisation
12 months
Admission for any cause
Time Frame: 12 months
Incidence of admission for any cause
12 months
Quality of life measured using Seattle Angina Questionnaire
Time Frame: 12 months
Quality of life measured using Seattle Angina Questionnaire at 24 hours post procedure, 1 month, 6 months and 12 months
12 months
Quality of life measured using EuroQoL-5D-5L questionnaire
Time Frame: 12 months
Quality of life measured using the EuroQoL-5D-5L questionnaire at 24 hours post procedure, 1 month, 6 months and 12 months
12 months
BARC 3-5 bleeding
Time Frame: 12 months
Incidence of Bleeding Academic Research Consortium (BARC) 3-5 classified bleeding as in-patient, and up to 12 months
12 months
Stroke
Time Frame: 12 months
Incidence of stroke
12 months
Cost effectiveness
Time Frame: 12 months
Cost effectiveness of immediate PCI versus standard care
12 months
Left ventricular ejection fraction on cardiac MRI
Time Frame: 7 days (+/-3 days)
Left ventricular ejection fraction on cardiac MRI
7 days (+/-3 days)
Infarct size on cardiac MRI
Time Frame: 7 days (+/-3 days)
Infarct size on cardiac MRI
7 days (+/-3 days)
Proportion of patients needing emergency/urgent revascularisation
Time Frame: 3-4 days (standard of care timing angiography will vary between recruiting centres)
Proportion of patients needing emergency/urgent revascularisation (in group B)
3-4 days (standard of care timing angiography will vary between recruiting centres)
Total access site complications
Time Frame: 12 months
Incidence of total VARC-2 classified access site complications as in-patient, and up to 12 months
12 months
Major access site complications
Time Frame: 12 months
Incidence of major VARC-2 classified access site complications as in-patient, and up to 12 months
12 months
Sensitivity and specificity of novel biomarkers for predicting need for revascularisation
Time Frame: 3-4 days (standard of care timing angiography will vary between recruiting centres)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospitals, Leicester

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of East Anglia
British Heart Foundation
University of Leicester

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Adrian Banning, Oxford University Hospitals NHS Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 6, 2018

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 28, 2021

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 28, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 13, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 15, 2018

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 16, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 10, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 8, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2022

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • EDGE 89678

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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