Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02789904 |
| Other study ID # |
2014/2182 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 5, 2015 |
| Est. completion date |
November 1, 2017 |
Study information
| Verified date |
October 2018 |
| Source |
National Heart Centre Singapore |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Current standard of care algorithm using high sensitivity troponin T (hsTnT) requires up to
6.5 hours to diagnose an ACS. Data will be stratified based upon time of symptom onset and
gender. A health economics and outcome model will be applied using the optimal high
sensitivity troponin I (hsTnI) cut-off values and draw times to determine the cost and
outcome benefits predicted from optimal utilization of hsTnI.
A chest pain registry will be set up to compare high sensitivity troponin I (hsTnI) versus
high sensitivity troponin T (hsTnT) for all patients who present to the emergency department
and require a blood draw. The outcomes of these patients will be tracked over the study
period.
The purpose of conducting this study evaluation is:
1. To shorten the chest pain protocol for suitable patients to < 3 hours compared to the
current 6 hours protocol with the latest high sensitivity Troponin I assays.
2. To determine the validity of Abbott ARCHITECT i2000 and Beckman Coulter ACCESS AccuTnI+3
with an accelerated algorithm in comparison to the standard of care acute coronary
syndrome (ACS) algorithm and high sensitivity troponin T (hsTnT) assay, to rule-out or
rule-in for an ACS within 3 hours of presentation to the emergency room (ER) with
isolated suspected ACS.
3. To establish the local reference norms for hsTnI assays.
Description:
Purpose
Current standard of care algorithm using high sensitivity troponin T (hsTnT) requires up to
6.5 hours to diagnose an ACS. Data will be stratified based upon time of symptom onset and
gender. A health economics and outcome model will be applied using the optimal high
sensitivity troponin I (hsTnI) cut-off values and draw times to determine the cost and
outcome benefits predicted from optimal utilization of hsTnI.
A chest pain registry will be set up to compare high sensitivity troponin I (hsTnI) versus
high sensitivity troponin T (hsTnT) for all patients who present to the emergency department
and require a blood draw. The outcomes of these patients will be tracked over the study
period.
The purpose of conducting this study evaluation is:
1. To shorten the chest pain protocol for suitable patients to < 3 hours compared to the
current 6 hours protocol with the latest high sensitivity Troponin I assays.
2. To determine the validity of Abbott ARCHITECT i2000 and Beckman Coulter ACCESS AccuTnI+3
with an accelerated algorithm in comparison to the standard of care acute coronary
syndrome (ACS) algorithm and high sensitivity troponin T (hsTnT) assay, to rule-out or
rule-in for an ACS within 3 hours of presentation to the emergency room (ER) with
isolated suspected ACS.
3. To establish the local reference norms for hsTnI assays.
Additionally, this study will also seek to validate the use of a 3-D Vector ECG system
developed by Ngee Ann Polytechnic, to see whether improved sensitivity and specificity for
the diagnosis of myocardial infarction on ECG can be achieved using vectorcardiography rather
than conventional 12-lead ECG recordings.
2.0 Scope
Under the current clinical algorithm at Singapore General Hospital, ambulatory chest pain
patients (CPP) receive an initial evaluation upon presentation to the ER that includes an ECG
and blood draw. The lab spins and holds the blood to await add-on orders for cardiac markers
if clinically-indicated. Other chest pain patients arriving by ambulance may have ECG taken
in the ambulance and the results faxed ahead to the ER. Those that have an initial ECG
consistent with an ST-elevation myocardial infarction (STEMI) receive immediate intervention.
Patients that do not have STEMI identified are evaluated by an ER physician as soon as
possible for clinical signs and symptoms of ACS, as well as, other diagnoses that require
clinical treatment and/or hospital admission. Patients with suspected ACS require serial
Troponin measurements as essential information for the rule-in or rule-out of a non-ST
elevation myocardial infarction (NSTEMI). After seeing the patient, the ER physicians will
add-on an hsTnT measurement to the sample drawn at presentation and held in the lab. This
second hsTnT value is drawn two hours after presentation. Using the current standard of care
hsTnT assay and the universal definition, an acute MI at Singapore General Hospital is
defined as a troponin rise and/or fall with at least one value above 30pg/mL with symptoms
suggestive of myocardial ischemia. There is no clear definition of the amount of rise or fall
that is required. The reference range for a single troponin T measurement at Singapore
General Hospital is currently defined as abnormal if above 30pg/mL. This study will compare
the ARCHITECT hsTnI assay and Beckman Coulter ACCESS AccuTnI+3 assays using respective Abbott
ARCHITECT and Beckman Coulter UniCel DxI 800 immunoassay systems, with hsTnT using Roche
analyzer.
Troponin I is a sensitive marker of myocardial necrosis, which will be elevated due to an
intraluminal coronary thrombus related to atherosclerotic plaque rupture or other spontaneous
coronary artery disease (CAD) event (MI Type I). STEMI patients will be excluded from this
study. The scope of this study will be limited to the rule-in and rule-out of NSTEMI in ER
patients with suspected ACS and no other known causes for elevated troponin.
Healthcare data sets and Singapore General Hospital cost data will be used to assess the cost
impact of an alternative model for NSTEMI diagnosis with a more aggressive hsTnI algorithm. A
30 day, Year 1, 2 and 5 follow-up phone contact in conjunction with medical record review and
screening data will be used by cardiologists to determine diagnosis and confirm patient
outcome.
Non-ST Elevation Myocardial Infarctions (NSTEMIs) have subtle changes in morphologies that
may not be obvious on a 12-lead ECG. This limits the 12-lead ECG's ability to affirmatively
indicate the presence or absence of NSTEMIs. The 3-D Vector ECG system developed by Ngee Ann
Polytechnic, which has similarities to vector cardiography (VCG, i.e. the Frank lead system)
is postulated to have better sensitivity to MI than the routine 12-lead ECG. Modern graphical
user interface techniques used by the 3-D Vector ECG system makes interpretation easier than
VCG. Additionally, since the electrode placements are identical to a 12-lead ECG. The
clinical procedure for acquiring the signals is not disrupted, increasing its viability for
integration into existing workflow.
3.0 Study Design and Procedures
Chest pain patients will be identified and consented in the ER waiting area following initial
triage and exclusion of STEMI and within 1 hour of initial blood draw at presentation. For
chest pain registry, coordinators will also invite NHCS inpatients to participate. The
Clinical Coordinators, under the guidance of Study Team investigators, will be responsible to
identify appropriate study candidates to join this study. They will assist the study team
investigators to explain the purpose of the study and obtain informed consent for additional
blood draws as well as a follow-up telephone/ medical records outcome survey. Patients will
be invited to join a registry where details regarding their clinical findings, relevant
investigations and clinical outcomes will be stored for possible future reference in a
database. Additionally, patients will also be asked if a 6-minute ECG can be performed on
them. The Clinical Coordinators will perform the 3 phlebotomy draws, which must occur within
the following window periods after the presentation draw to be included in the study:
Draw Window period after presentation draw 0h 0-30 min
1. h 60-90 min
2. h 120 - 150 min
Specimens will be collected in 5.0 ml Gel tubes (Serum Separator Tube). A total of
approximately 15 ml of blood will be collected from each patient. The blood sample will be
processed at National Heart Centre Singapore (NHCS) laboratory. The clinical coordinators
will store each patient's serum into 2 separate vials and freeze them in the freezer at
≤-80°C. The frozen serum samples will be used to perform the hsTnI assays on the Abbott
ARCHITECT i2000 analyzer in NHCS and the ACCESS AccuTnI+3 assays on the Beckman Coulter
UniCel Dxl 800 analyzer in SGH Pathology by the study coordinator and SGH Pathology lab staff
respectively.
The screening Case Report Form is required for completion and will gather information on 3
key elements: 1) chest pain onset/characteristics; 2) comprehensive demographics to describe
the study population; and 3) data for TIMI risk score generation (Appendix I).
To assess the use of 3D-Vector ECG, a target of 1000 12-lead ECGs are to be retrieved from
the electrocardiographs at SGH Emergency Department triage, with the post-analysis to be done
at NHCS. The retrieved ECGs will be converted to 3D-vector ECG and analysed to extract
discriminating parameters which can be reliably used to diagnose and localise the presence of
ischaemia. Accuracy of the diagnoses will be counter checked with the results of further
diagnostic tests performed on the patient in the normal course of treatment. From the
analysis of these 1000 records, the sensitivity and specificity of the 3D-Vector ECG to
localise acute coronary syndrome will be computed.
4.0 Lab Test Orders, Blood Draws, and Analysis
After clinical assessment of the patient by an ER physician, an add-on troponin may be
ordered for clinical purposes by the physician that will be applied to the time zero
"presentation" blood draw. Likewise, a 2-hour troponin may be ordered for clinical purposes.
Analysis of Beckman Coulter ACCESS AccuTnI+3 assays will take place on UniCel DxI 800
immunoassay system in the Singapore General Hospital (SGH) Pathology. Analysis of ARCHITECT
hsTnI assay will take place on Abbott ARCHITECT i2000 analyzer in the National Heart Centre
Singapore (NHCS) Laboratory. Calibration, Calibration verification, cross-over validation,
and daily Quality Control for the hsTnI assay will be performed by medical technologists in
conjunction with normal laboratory operations.
6.0 Study Duration
4,000 patients are expected to have been included in the study in a period of 5 years from
the day of recruitment. Recruitment of new patients will end after 4,000 patients are
enrolled.
7.0 Data Retrieval
Laboratory data will be stored in the SingHealth Information System. Extraction of the data
will be accomplished by export to an Excel spreadsheet. Clinical data will be printed out and
entered into a computer database using a standardized case report form.
8.0 Telephone/ Medical records Follow-up
Study patients will be contacted by telephone/ medical records on Day 30, Year 1, Year 2 and
Year 5 after recruitment for any clinical events or symptoms that will be relevant to
adjudication.
