Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02879032 |
| Other study ID # |
MAlam-01 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 2016 |
| Est. completion date |
July 1, 2017 |
Study information
| Verified date |
October 2019 |
| Source |
Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Exercise treadmill test (ETT) is frequently done, inexpensive, relatively safe investigation
for diagnosis of ischemic heart disease and prediction of exercise capacity. Ischemic heart
disease is increasing by leaps and bounds all over the world even in the developing countries
like Bangladesh. The incidence rate of coronary artery disease (CAD) is not limited to male
gender as previously seen. As a cause of industrialization and increased life expectancy,
incidence of ischemic heart disease in females is escalating now in Bangladesh also. Though
ETT is a well accepted investigation to diagnose CAD, it has a high false positive and false
negative result if ST segment response alone is calculated for interpretation of the test.
Duke Treadmill Test and Simple Treadmill Test are valid and well known scores which can
predict coronary artery disease burden more efficiently than ST segment response alone.
Computer generated Cleveland clinic score is another valid treadmill score which has a
complex algorithm but effective way to predict 3 year and 5 year survivability. These three
scores are well tested on western population but to our best knowledge there is little or no
information regarding their predictability of CAD in Bangladesh. It's well known that ETT has
a high false positive result in female population, so applying the scores may render ETT more
efficient and abrogate unwanted risk of undergoing coronary angiography to diagnose CAD in
females. In this study the investigator will try to find out the accuracy of commonly applied
treadmill scores and ST segment response to diagnose CAD as well as accuracy of computer
generated Cleveland Clinic Score will be tested. Total 110 people including male and female
will be included according to inclusion and exclusion criteria and informed written consent
will be taken. The patients who have undergone ETT and coronary angiogram with in six months
for confirmation and identification of coronary artery disease in accordance with the
recommendation of ACC guideline for CAG will be selected . All available data will be
analyzed using SPSS. The accuracy of different scores will be calculated and compared with
each other. According to currently available data from studies in western population the
treadmill scores will have good predictability and will be efficient to abolish high false
positive result in female population in Bangladesh.
Description:
Introduction At present several treadmill scores have been proposed as means for improving
the diagnostic accuracy of the exercise treadmill test (ETT) and to predict future risk of
cardiac events (Berman et al., 1978 & Do et al., 1997). Although a large number of
noninvasive stress testing modalities are currently available, the exercise ECG is still used
as a standard for comparison with other clinical and testing risk markers. It is also the
least costly of all provocative noninvasive tests. The Duke Treadmill Score (DTS),
traditionally a prognostic score, was recently tested as a diagnostic score and shown to
predict CAD better than the ST response alone(Shaw et al., 1998). But questions remain
regarding the diagnostic accuracy of treadmill scores when applied to a different patient
population; furthermore, many treadmill scores have not been compared with one another in the
same population(Fearon et al., 2002).To date, no composite stress-test score or noninvasive
risk index has been shown to provide both accurate diagnostic and prognostic risk estimates.
Despite that exercise treadmill test remains a useful test for diagnosing coronary artery
disease (CAD) in patients with chest pain and at intermediate risk for CAD (Do et al.,
1997).The sensitivity and specificity of ETT varies considerably. According to a
meta-analysis conducted by Gianrossi et al there was a wide variability in sensitivity and
specificity of ETT [sensitivity 68± 16% (range 23-100%); specificity 77±17% (range: 17-100%).
Another Meta analysis showed sensitivity of 81± 12% (range: 40-100%) and specificity of 66±
16% (range: 17-100%) (Myers et al., 1994).Fearon WF et al showed sensitivity and specificity
was higher when treadmill scores were applied in comparison to ST response alone. They used a
consensus score consisting of the Morise, Dentrano and VA score and found predictive accuracy
of the consensus score for stratifying patients to low and high likelihood for CAD was
significantly higher than the predictive accuracy of DTS, 80(74-86)% versus 71(65-77)% (p<
0.0001). But Fearon WF et al conducted the study only on male population in USA and the
consensus score was calculated by average of computer generated treadmill scores. In 2012 Mao
L et al have shown 73 out of 104 male patients were detected CAD both by ETT and CAG, the
accuracy rate was 70.2% which was much higher than that (50.0%) of the female patients
(p<0.05) and they only used ST changes alone to demonstrate ETT positivity In this study, we
will compare the diagnostic accuracy of well known prognostic scores namely, Duke Treadmill
Score, Simple Treadmill Score and Cleveland Clinic Score to identify significant coronary
artery lesion in Bangladeshi male and female patients.
Rationale
Though exercise treadmill test has high false positive and negative rates(Zang et al., 2007)
, it is cheap, easily available, less time consuming to the interpret results and its
accuracy can be increased by calculating ST/HR index, treadmill score, QT dispersion and so
on (Kronander 2010 &Dentrano 1989). On the contrary the gold standard test coronary angiogram
for detecting CAD is expensive, time consuming, potentially hazardous with many complications
and often the CAG shows normal coronary arteries in female population.ST-segment depression
and chest pain as the classic criteria for CAD diagnosis are well known and accepted. Besides
If treadmill score were used the diagnostic accuracy of ETT would had been higher. The
accuracy of different treadmill scores in Bangladeshi population especially the female
population is largely unknown. Duke Treadmill Score and Simple Treadmill Score are well
validated score in western population and are used for diagnostic & prognostic interpretation
of ETT. The predictive accuracy of DTS to diagnose CAD is 71% (Fearon 2002). In 2001 Raxwal V
et al. showed simple treadmill score has sensitivity of 88% and specificity of 96%. If we
calculate the accuracy of simple treadmill score using the formula "Accuracy = (Sensitivity)
x Prevalence + (Specificity) x (1- Prevalence)" it sums up nearly 93% according to prevalence
of CAD in urban population. Cleveland Clinic Score is a prognostic score of ETT. It gives
value from which we can predict the probability of 3 year or 5 year survival. It was shown
that it has a very high negative predictive value approaching 97%. Besides to the best of our
knowledge Cleveland Clinic Score was not tested as a diagnostic predictor of CAD and there
are few studies regarding treadmill scores predictability in Bangladesh. In our study we will
use all of these three scores and compare their accuracy to predict significant CAD. DTS,
Simplified Treadmill Score, and Cleveland clinic score can be implemented effectively to
identify patients with low probability of CAD and excluded from undergoing expensive and
potentially hazardous CAG if the real scenario of the treadmill scores is known in our
population.
Research question
Howdo different treadmill scores (Duke Treadmill Score, Simple Treadmill Score, Cleveland
Clinic Score) vary to predictability of Coronary Artery Disease in Bangladeshi population in
a tertiary care hospital?
General Objectives
To identify difference of predictability of DTS, Simple Treadmill Score and Cleveland Clinic
Score to diagnose significant CAD by Coronary Angiography.
Specific Objectives
1. To estimate accuracy of ST segment response, DTS, Simple Treadmill Score and Cleveland
Clinic Score to predict CAD.
2. To compare DTS, Simple treadmill score, Cleveland Clinic Score accuracy to predict
coronary artery disease.
3. To identify the relation of different level of treadmill scores with severity of CAD.
Study Area
University Cardiac Center, Bangabandhu Sheikh Mujib Medical University (BSMMU). BSMMU is a
renowned institute in Bangladesh with good indoor and outdoor facility. It also has good
inpatient and outpatient services for local and other patients coming from distant places.
There is a good mix of male and female patients also which is needed to test the study
hypothesis. Overall, the patients coming in outdoor facility to get treatment represent the
Bangladeshi population very well and uniformly.
Sampling Procedures
Patient presented with stable chest pain, who have undergone ETT according to Bruce protocol
and admitted for CAG, will be selected as case considering inclusion and exclusion criteria.
Detailed and thorough clinical assessment will be done and recorded. All available previous
medical documents will be checked meticulously. Patients with previous revascularization,
left bundle-branch block, paced rhythms or Wolff-Parkinson-White syndrome (WPW) on resting
electrocardiogram (ECG), or valvular heart disease, congenital heart disease will be excluded
from the study. To avoid falsely increasing the accuracy of the exercise treadmill test,
patients with a previous myocardial infarction by history or by diagnostic Q wave will be
excluded.
With history, clinical findings and investigations cases other than stable chest pain will be
excluded. Informed written consent will be taken from the patient. CAG report will be
collected from the Cath lab after the procedure.
Data collection:
Data will be recorded in pre-designed questionnaires by history, clinical examination and
investigation with the patient of University Cardiac Center, BSMMU.
Quality assurance strategy:
A set of questionnaire will be formulated & checked. To make the study credible, reliable &
dependable data will be collected by principal investigator by using those questions over a
month of period. Again the questions will be edited accordingly & necessarily after
discussion with the guide and co-guide of this study.
Ethical Issues At first ethical clearance will be taken from the ethical review committee of
Bangabandhu Sheikh Mujib Medical University (BSMMU). The study will be carried out according
to 1964 Helsinki Declaration for Medical Research involving Human subjects and amended by the
64th World Medical Association General Assembly, October 2013. No drugs or placebo will be
used for this study. Each participant will enjoy every right to participate or refuse
participation. They will be free to withdraw their participation at any stage of the study.
Data taken from the participants will be regarded as confidential. Data will be used only for
this scientific study. Participants will be informed in detail about the nature and purpose
of the study, and informed written consent will be taken from each participant.
Sample size calculation
Sample size is calculated by using the following equation (One sample comparison of
proportion):
n=⌈Zβ√(p(1-p) )+Zα√p1(1-P1)⌉^2/((p-p1)²) n = required sample size p = Proportion under
alternative hypothesis that is proposed to be detected or worst possible outcome p1=
Proportion under null hypothesis or proportion in the population Zα = 1.96 (5% level of
significance) Zβ = 1.28 when power is 0.9 According to Fearon WF et al (2002) the predictive
accuracy of DTS is 71% (0.71).
If we assume: p1= 0.71 P = 0.55, Power = 0.8, α = 0.05 Sample size n =
⌈1.28√(.55(1-.55) )+1.96√(.71(1-.71))⌉^2/((.55-.71)²) = 91
Correction for non-response:
Nf=100/100- Nr If Nr= Percentage of expected non-response is 10% Nf=100/100- 10 = 1.11 Final
sample size will be estimated sample size (n) x Nf = 91 x 1.11 = 102. So our required sample
size is at least 102.
StatisticalMethods Using angiographic evidence of CAD as the reference, area under the curve
(AUC) of receive operator characteristic (ROC) plots will be determined for the ST response
alone and for each treadmill score. The AUC for each treadmill score will be compared with
the AUC of the ST response alone and the AUCs of the other treadmill scores. The predictive
accuracies of the DTS, the Simple Treadmill Score and Cleveland Clinic Score to stratify
patients into high or low likelihood for CAD will be calculated and compared. Statistical
analysis will be performed with the SPSS.
