Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000550606
Ethics application status
Approved
Date submitted
12/05/2014
Date registered
22/05/2014
Date last updated
21/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The Australian Grace Risk score Intervention study (AGRIS): a hospital level cluster randomised clinical trial with blinded endpoint evaluation which aims to enhance evidence based decision making and outcome delivery of Australian Acute Coronary Syndrome (ACS) care by evaluating a GRACE Risk score based decision support tool versus standard care
Scientific title
The Australian Grace Risk score Intervention study (AGRIS) is a hospital level cluster randomised clinical trial with blinded endpoint evaluation which aims to enhance evidence based decision making and outcome delivery of Australian Acute Coronary Syndrome (ACS) care by evaluating a GRACE Risk score based decision support tool versus standard care.
Secondary ID [1] 284451 0
Nil known
Universal Trial Number (UTN)
U1111-1156-2155
Trial acronym
Australian Grace Risk Implementation Study (AGRIS)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Coronary Syndromes 291651 0
Condition category
Condition code
Cardiovascular 292054 292054 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The Australian GRACE Risk Intervention Study is assessing risk stratification in acute coronary syndrome patients using the Grace Risk Score and treatment recommendation tool (GRS) versus standard patient care.
The Grace Risk tool includes calculation of ischaemic and bleeding risk scores, a nomogram to assess patient risk / benefit, a treatment recommendation plan (based on guideline recommended investigations and therapies) and documentation of physician intended therapies. Based on the risk scores, patients are categorized into low, intermediate or high risk of ACS and bleeding and physicians are directed to recommended investigations and treatments according to the level of risk. This paper based tool is completed and placed into the patient's medical records early in the patient assessment process. It is then reviewed by the treating physician to acknowledge that the recommendations have been considered.
Following a 3 month implementation period where hospital staff are trained on use of the tool, patients will commence entry into the study. Post implementation, sites will be followed up to confirm continued use of the tool. A clinical champion will be identified at each site to assist in implementation of the tool. A copy of the completed patient GRS will be submitted to the coordinating group.
Each site will enrol 80 patients (approximately 10 patients per month). The duration of the intervention period will therefore be 12-18 months according to patient recruitment.
This study will also employ a Data Safety Monitoring Committee to evaluate blinded study endpoints in each of the 2 groups.
Intervention code [1] 289195 0
Prevention
Intervention code [2] 289424 0
Treatment: Other
Comparator / control treatment
Standard care administered by hospital physicians to patients admitted with an Acute Coronary Syndrome.
Control group
Active

Outcomes
Primary outcome [1] 291920 0
Evaluate the effectiveness of risk stratification using the GRACE Risk tool and treatment recommendation plan for ACS patients on the in-hospital use of evidence-based investigations and therapies and secondary prevention assessed at the time of discharge.
Data is extracted from the medical records and entered into an electronic Case Report Form.
The primary (hospital performance measure) endpoint will be the composite endpoint of adherence to performance measures (receipt of angiography; receipt of 4/5 recommended therapies and referral to cardiac rehabilitation) by the time of discharge among those patients discharged alive.
Timepoint [1] 291920 0
At discharge from hospital admission.
Secondary outcome [1] 307819 0
To determine the incremental net clinical benefit and cost-effectiveness of risk stratification using the GRACE Risk tool and treatment recommendation plan on care within the routine clinical environment.
Data is extracted from the medical records and entered into an electronic Case Report Form.
Cost effectiveness will be measured by data linkage to the Medicare Benefits Scheme and Pharmaceutical Benefits Scheme and Quality of Life (EQ5D) as completed by the patient.
Timepoint [1] 307819 0
This secondary objective will be measured on discharge from hospital.
Secondary outcome [2] 307820 0
To determine the incremental net clinical benefit of risk stratification using the GRACE Risk tool and treatment recommendation plan on the reduction of cardiovascular death, myocardial infarction, new or worsening heart failure, and readmissions for cardiovascular or significant bleeding at 12 months.
Data is obtained via patient follow up 12 months post admission to hospital.
Timepoint [2] 307820 0
This will be measured at 12 months post discharge from hospital.

Eligibility
Key inclusion criteria
Hospital-level Inclusion criteria:

* Admit at least 15 ACS patients a month.
* The presence of an onsite 24/7 emergency service.
* ED, Cardiology/medicine services willing to implement the GRACE Risk tool and treatment recommendation plan into their care process.

Patient Level Inclusion Criteria:
Patients are eligible if they present to hospital with symptoms felt to be consistent with acute cardiac ischaemia for >10mins within 24 hours of presentation to hospital plus one of the following: ECG changes; elevated enzymes; documentation of CAD or documentation of 2 or more features of high risk ACS:

ECG changes:
-transient ST segment elevation of 0.5mm in two or more contiguous leads;
-ST segment depression of 0.5mm in two or more contiguous leads
-new T wave inversion of 1 mm in two or more contiguous leads
-new Q waves (1/3 height of R wave or >0.04 seconds)
-new R wave > S wave in lead V1 (posterior MI)
-new left bundle branch block

Increase in cardiac enzymes:
-increase in troponin T above the upper limit of normal
- increase in troponin I above the upper limit of normal;
CKMB
-2x upper limit of the hospitals normal range or if there is no CKMB available, then total CK greater than the upper limit of normal.

Documentation of Coronary Artery Disease
- history of MI, angina, congestive cardiac failure due to ischaemia or resuscitated sudden cardiac death
-history of or new positive stress test with or without imaging;
- prior or new, cardiac catheterisation documenting coronary artery disease
- prior or new percutaneous coronary artery intervention or coronary artery bypass graft surgery

At least 2 of the following High Risk features:
- haemodynamic compromise (BP<90 and HR >100)
-left ventricular systolic dysfunction (LVEF<0.40);
-presence of known diabetes
-documentation of chronic kidney disease (estimated GFR <60mls/min
Minimum age
18 Years
Maximum age
120 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Hospitals with an existing implemented risk stratification support system for the management of ACS patients will be excluded.

Patients presenting to hospital with an ACS accompanied with, or precipitated by significant co-morbidity e.g. motor vehicle accident, trauma, severe gastrointestinal bleeding, peri-operative or peri-procedural MI will be excluded and patients already hospitalised for any reason when the ACS develops are
not eligible for enrolment in the registry.

Patients already recruited into the study can only be re-enrolled after the 12 month follow up period has been reached.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
In the existing CONCORDANCE data set 6561 are confirmed ACS patients. Of these confirmed ACS patients 2326 (35.5%) are classified as high-risk patients (GRS greater than 118).
Each of the three indices of guideline adherence is given a score of one, i.e. inpatient angiography=1, discharge on optimal medical therapy=1, and rehabilitation referral=1. Thus a patient meeting all three indices of guideline adherence would have a total score of 3.
A sample size of 12 sites per group with 28 high risk patients per site achieves an 80% power to detect a difference in the total score of 0.5 between the group means when the standard deviation is 0.92 and the intra-cluster correlation is 0.176 using a Two-sided T-test with a significance level of 0.05.

Therefore, this study will enroll 28 high-risk patients per site or 336 patients per arm. However, it will be important to recruit all patients presenting with an ACS diagnosis regardless of risk as their management will also likely be influenced by the intervention and the benefits of some recommendations (like angiography) are not as well established in this group. Thus the samples size will be 947 patients per arm or 1894 in total. Outcomes in this whole cohort will be assessed as a secondary endpoint.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/09/2014
Actual
1/09/2014
Date of last participant enrolment
Anticipated
15/09/2017
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
1900
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,NT,QLD,SA,WA,VIC
Recruitment hospital [1] 2334 0
Concord Repatriation Hospital - Concord
Recruitment hospital [2] 2335 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [3] 2481 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [4] 2482 0
The Alfred - Prahran
Recruitment hospital [5] 2483 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [6] 2484 0
Liverpool Hospital - Liverpool
Recruitment hospital [7] 2485 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [8] 2486 0
Royal Darwin Hospital - Tiwi
Recruitment hospital [9] 5924 0
Wollongong Hospital - Wollongong
Recruitment hospital [10] 5925 0
Shoalhaven Hospital - Nowra
Recruitment hospital [11] 5926 0
Bathurst Base Hospital - Bathurst
Recruitment hospital [12] 5927 0
Royal Hobart Hospital - Hobart
Recruitment hospital [13] 5928 0
Westmead Hospital - Westmead
Recruitment hospital [14] 5929 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [15] 5930 0
St George Hospital - Kogarah
Recruitment hospital [16] 5931 0
Port Macquarie Base Hospital - Port Macquarie
Recruitment hospital [17] 5932 0
The Canberra Hospital - Garran
Recruitment hospital [18] 5933 0
Nepean Hospital - Kingswood
Recruitment hospital [19] 5934 0
Alice Springs Hospital - Alice Springs
Recruitment hospital [20] 5935 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [21] 5936 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [22] 5937 0
Orange Health Service - Orange

Funding & Sponsors
Funding source category [1] 289093 0
Commercial sector/Industry
Name [1] 289093 0
Astra Zeneca
Country [1] 289093 0
Australia
Primary sponsor type
Government body
Name
Sydney Local Health District - Concord Hospital
Address
Hospital Road
Concord NSW 2139
Country
Australia
Secondary sponsor category [1] 287764 0
None
Name [1] 287764 0
Address [1] 287764 0
Country [1] 287764 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290880 0
SLHD Human Research Ethics Committee-Concord Hospital
Ethics committee address [1] 290880 0
Ethics committee country [1] 290880 0
Australia
Date submitted for ethics approval [1] 290880 0
Approval date [1] 290880 0
19/03/2014
Ethics approval number [1] 290880 0
HREC/13/CRGH/220

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 47738 0
Prof David Brieger
Address 47738 0
Cardiology Department,
Concord Hospital
Hospital Road
Concord NSW 2139
Country 47738 0
Australia
Phone 47738 0
+ 61 2 97676296
Fax 47738 0
Email 47738 0
[email protected]
Contact person for public queries
Name 47739 0
Colette Beck
Address 47739 0
Cardiology Research
Level 1, Medical Centre
Hospital Road
Concord Hospital
Concord NSW 2139
Country 47739 0
Australia
Phone 47739 0
+61 2 9767 5539
Fax 47739 0
Email 47739 0
[email protected]
Contact person for scientific queries
Name 47740 0
David Brieger
Address 47740 0
Cardiology Department,
Concord Hospital
Hospital Road
Concord NSW 2139
Country 47740 0
Australia
Phone 47740 0
+61 2 97676296
Fax 47740 0
Email 47740 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseA cluster randomized trial of objective risk assessment versus standard care for acute coronary syndromes: Rationale and design of the Australian GRACE Risk score Intervention Study (AGRIS).2015https://dx.doi.org/10.1016/j.ahj.2015.07.032
EmbaseObjective Risk Assessment vs Standard Care for Acute Coronary Syndromes: A Randomized Clinical Trial.2021https://dx.doi.org/10.1001/jamacardio.2020.6314
N.B. These documents automatically identified may not have been verified by the study sponsor.