Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05156736 |
| Other study ID # |
PAKSEHAT |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 15, 2023 |
| Est. completion date |
November 2028 |
Study information
| Verified date |
April 2023 |
| Source |
Tabba Heart Institute |
| Contact |
Bashir Hanif, FSCAI |
| Phone |
+92-21-36811841 |
| Email |
bashir.hanif[@]tabbaheart.org |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Coronary heart disease (CHD) is a major cause of morbidity, disability, mortality, and health
expenditures worldwide. A wealth of studies has demonstrated that people of South Asian
ancestry have a higher risk of CHD and particularly premature CHD than most other
racial/ethnic groups, and recent research suggests that this risk is higher in Pakistanis
than in Indians-the two largest SA groups. Pakistan is the 5th most populous country in the
world, and despite these concerning trends, so far there has been a scarcity of large studies
evaluating the prevalence of cardiovascular risk factors and subclinical coronary
atherosclerosis in young-to-middle-aged Pakistanis. Also, there is currently no
cardiovascular risk score specifically tailored to younger Pakistani men and women. The
PAKistan Study of prEmature coronary atHerosclerosis in young AdulTs (PAK-SEHAT) aims at
addressing these important gaps. PAK-SEHAT is an ongoing prospective cohort study that will
enroll 2,000 asymptomatic Pakistani men aged 35 to 60 years and women aged 35 to 65 years
from the general population, free of clinically overt cardiovascular disease. Participants
will undergo a comprehensive baseline exam including coronary computed tomography
angiography, and will be followed for incident events and repeat testing for 5 years.
PAK-SEHAT will allow determining the prevalence, severity, determinants, and prognostic
significance of early atherosclerosis in apparently healthy young-to-middle-aged Pakistanis.
This knowledge can help inform primordial and primary prevention strategies, enhanced
cardiovascular risk stratification, and potential plaque-screening approaches in Pakistan,
all of which can ultimately help reduce the burden of CHD in the country. In this report
investigators describe the rationale, objectives, methods, and discuss the potential
implications of the PAK-SEHAT study.
Description:
Study Objectives The primary objectives of PAK-SEHAT are: 1) characterize the prevalence and
severity of subclinical coronary atherosclerosis among young-to-middle aged Pakistani men and
women free of clinical CVD, and 2) assess 5-year rates of ASCVD events. The secondary
objectives of the study are to 1) determine the prevalence of diabetes, hypertension,
dyslipidemia, and other cardiovascular risk factors among young Pakistani men and women free
of clinical CVD; 2) identify the determinants of subclinical coronary atherosclerosis in this
population; 3) estimate the incidence of diabetes, hypertension, dyslipidemia, and other
cardiovascular risk factors at 5 years of follow-up; 4) identify independent risk factors and
markers of incident clinical ASCVD among young asymptomatic Pakistanis.
Study Design PAK-SEHAT is a prospective cohort study, with a target study population of 2,000
participants and a planned prospective follow-up of 5 years after study enrollment.
Study Population Investigators plan to recruit 2,000 young-to-middle aged adult Pakistani men
and women with no known clinical ASCVD. Because the focus of this study is to investigate the
prevalence, severity, and determinants of early coronary atherosclerosis in Pakistani adults,
focus will be on apparently healthy (i.e., without known clinical CVD) young-to-middle native
Pakistanis. Also, because premature coronary events are more frequent and usually observed at
younger ages in men than in women, the age range of male participants at enrollment will be
35-60 years, while this will be 35-65 years for female participants; and enrollment will use
a 1:1 male:female ratio.
Sampling Strategy: PAK-SEHAT aims to be as representative as possible of the general
Pakistani population, and a multi-stage cluster sampling strategy will be used to identify
candidates to participate in the study. The first stage of the sampling process occurs at the
province level, which is the largest administrative division in the country, and participants
will be recruited from all four Pakistani provinces and the Federal territory of Islamabad. A
cluster is defined as the selected tertiary care hospital offering clinical cardiac services.
The selection criteria of hospital include clinical cardiac services being provided and
availability of CT coronary angiogram. Next, cities are selected, and within those, the
hospitals. The distribution of the sample across the provinces was done proportionate to the
size sampling method. We are collaborating with eight hospital sites across the country to
achieve our sample size. Tabba Heart Institute Karachi, Safari Hospital Rawalpindi, Bahria
international Hospital Lahore, Doctors Hospital and medical center Lahore, Faisalabad
Institute of Cardiology, Medikay Cardiac Center Islamabad, Peshawar Institute of Cardiology
and Tabba Heart Institute Quetta.
Participant Enrollment The attendant of the patients admitted to the hospital will be offered
to participate in the study. The volunteers for the study will be recruited through
advertisement of the study using pamphlets, posters, electronic medium such as FM radio and
digital platforms such as facebook, twitter, and instagram. Individuals who are deemed
eligible to participate in the study will be provided with detailed information about the
study, invited to ask questions, and asked to provide written informed consent for
participation.
All the participants will undergo study measurements that include an interview about current
past clinical history, family history, lifestyle, and mental health assessment, laboratory
investigations such as lipid profile, liver profile, HbA1C, CBC, CRP, Renal function tests,
and Lp (a). The participants will undergo CT angio and cIMT measurement at the respective
hospital sites and will be provided with their reports. The central reporting of CT angio and
cIMT will be done at TabbaHeart by two readers to standardize the measurements.
At 2.5 year follow-up, laboratory investigations will be repeated and 5 year CT angio along
with laboratory investigations will be repeated. In between the baseline and follow-up,
participants will be contacted regularly to collect data on cardiac events.
Study interview and questionnaires. Participants will be interviewed by trained study
personnel. Sociodemographic data, and information on past and present medical history, family
history, lifestyle will be collected using structured questionnaires.
Blood pressure: Systolic and diastolic blood pressure will be measured in each participant
using Omron digital BP apparatus, with participants sitting in a comfortable position for 5
minutes.
Anthropometry and body composition. Height (cm) will be measured through height scale. Body
composition will be analyzed using the Tanita-MC-780 U body composition analyzer.
Blood measurements and genetics. Trained study personnel will draw approximately 30 mL of
venous blood from each participant. Approximately 10 mL of blood will be biobanked and stored
at -80C to allow for future additional research studies, including genetic testing. The
latter will include but not limited to testing for ApoE Genotype (information about risk of
heart disease and response to amounts of dietary fat), 9p21 Genotype (risk of MI and CAD at
an early age), KIF6 Genotype (risk of heart disease and reduction of MACE with statins), LPA
Intron 25 (increased risk of heart disease), 4q25 A-Fib genotype (risk of atrial fibrillation
and risk of stroke due to atrial fibrillation). In participants who do not consent for
genetic testing, their 10 mL of biobanked blood may be used in non-genetic analyses but not
for studies involving genetic testing.
Cardiac CT scans. Participants will first undergo a non-contrast-enhanced cardiac CT for
coronary artery calcium (CAC) scoring, followed by a contrast-enhanced CCTA. Toshiba Aquilion
Multislice CT scanners and prospective ECG triggering will be used. Participants will be
evaluated before the CT scan by study personnel and if the heart rate is above 65 bpm will be
pre-treated with a β-blocker (or ivabradine if contraindicated) to achieve a target heart
rate of ~60 bpm. Sublingual nitroglycerin will be administered as per standard protocols
approximately 3 minutes before the CCTA scan, and intravenous contrast will be injected at a
rate of 5.5-7 ml/s depending on the body habitus of the participant; for an average patient,
the dose of contrast is expected to be approximately 60-80 mL. The non-contrast-enhanced
images will be transferred to the Cardiology CT core lab at Tabba Heart Institute and
evaluated by trained radiologists who will quantify CAC according to Agatston's method.
Carotid ultrasound imaging . All participants will undergo carotid ultrasound imaging for
assessment of presence of carotid plaque and for carotid intima-media thickness (CIMT)
evaluation. This will be assessed with automated measurement over bilateral carotid arteries
using a Toshiba Aplio 500 ultrasound system (Otawara, Japan), using B-mode ultrasound
examination with a 10-MHz multi-frequency linear array transducer. Participants will be
examined in the supine position, and standard measurements will be performed.
Baseline Data Management and Quality Study data will be collected in tablets and other
digital platforms and will be transferred to a central server. The centralized study database
will be stored at the Tabba Heart Institute using a secure server, and data privacy and
confidentiality will be secured at all times. For quality control purposes, the data
collection application in the tablets will have built-in features to limit erroneous data
entry and inconsistency in recording participants' responses. Also, a field coordinator will
monitor data collection and spot-check 5-10% of the interviews. At the centralized study
database, data error reports will be generated on a monthly basis to monitor completeness,
invalid values, and inconsistencies in responses. In addition, a live dashboard will be
developed for pre-identified key variables to monitor and evaluate the project's progress.
Follow-Up and Event Ascertainment: Besides repeat blood tests and imaging testing at 30 and
60 months (Table 2), in each of the three follow-up visits a questionnaire will be used to
collect information on ASCVD outcomes. In case of an affirmative answer, participants will be
asked to provide additional evidence (e.g. hospital admission records) so that the event can
be confirmed. ASCVD events will include myocardial infarction, unstable angina, stable
angina, stroke, transient ischemic attack, coronary revascularization, and cardiovascular
death.
Published definitions will be used to define each of these incident events. Independent two
cardiologists from the centralized PAK-SEHAT adjudication committee and blinded to the
results of the study tests will classify events as definite, probable, or absent, based
primarily on available hospital documentation. They will also classify CHD-, CVD- or stroke-
related deaths based on hospital records (if available) and verbal autopsy interviews with
families. If there is disagreement in event adjudication between the 2 assigned experts, a
third independent physician adjudicator will review the evidence to break the tie.
The repeat CCTA at 60 months of follow-up will be used to evaluate the progression/regression
of coronary plaque burden.
Statistical Analyses For analyses using baseline data, the frequency and distribution of
cardiovascular risk factors (known, unknown), coronary plaque burden, and other key baseline
variables using number and frequency (%) for categorical variables and mean (standard
deviation) or median (interquartile range) for normally and not normally distributed
continuous variables will be described. Specifically for coronary plaque characteristics, the
CAC score will be categorized as 0, >0-<100, ≥100, and the distribution of CAC scores and
proportion of each stratum will be reported. With regards to CCTA findings, the proportion of
participants with any coronary plaque and the distribution of plaque subtypes will be
reported with 95% CI. Investigators will also report the frequency of having maximal coronary
stenosis ≥50% and ≥70%, respectively, and the proportion of participants with high-risk
plaque features. The distributions of the number of coronary vessels with plaque, the number
of coronary segments affected per participant, and the location of coronary plaques (left
main, anterior descending, circumflex, and right coronary artery) will also be described.
In analyses of incident events during follow-up, investigators will use standard survival
analysis and time-to-event techniques. Cumulative incidence at 5 years (in %) and incidence
rates per 1,000 person-years (with 95% CI) will be computed for the primary and secondary
study outcomes. The ASCVD event rates in the PAK-SEHAT population will be compared with those
of Pakistanis of the same age and sex free of clinical ASCVD and not included in the study.
Analyses of the incidence of cardiovascular risk factors during follow-up will be restricted
to individuals at-risk of each of those risk factors.
Investigators will use Cox Proportional Hazards regression models to evaluate the association
between important baseline characteristics and incident ASCVD events during follow-up.
