Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02958657 |
| Other study ID # |
12163 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 30, 2016 |
| Est. completion date |
March 31, 2019 |
Study information
| Verified date |
March 2021 |
| Source |
University of Sao Paulo General Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This project aims to evaluate, in recent post-acute myocardial infarction (AMI) patients on
dual antiplatelet therapy, the impact of regular exercise training on platelet aggregability
and the correlation between the level of platelet aggregability and muscle sympathetic nerve
activity (MSNA).
Description:
1. Introduction:
Platelet reactivity is closely involved in the pathophysiology of acute coronary
syndromes (ACS). However, despite the development of newer and more effective
antiplatelet drugs (among other therapeutic interventions), the risk of ischemic events
recurrence after an episode of ACS is still high.
On the other hand, acute and strenuous exercise, a known trigger of ACS, when performed
by untrained individuals, leads to sympathetic hyperactivity and increased platelet
aggregability. Contrary to these findings, regular supervised exercise training leads to
regulation of the autonomic system with consequent decrease in the incidence of ACS, as
shown in previous studies. However, the relationship between regular supervised exercise
training on platelet activity in patients post-AMI on dual antiplatelet therapy, has not
been previously studied and is the main goal of the present project.
2. Objectives:
This project aims to evaluate, in recent post-AMI patients on dual antiplatelet therapy,
the impact of regular exercise training on platelet aggregability, analyzed by
VerifyNowP2Y12® test. Secondary exploratory analysis includes: 1) the influence of acute
and strenuous exercise on platelet aggregability measured immediately after the two
cardiopulmonary exercise testing (CPET) that patients will be submitted; 2) the
correlation between the level of platelet aggregability and MSNA in trained and control
groups; 3) the influence of exercise training on platelet aggregability measured by
Multiplate® adenosine diphosphate (ADP) test and Multiplate® aspirin (ASPI) test; 4) the
influence of exercise training on the mean platelet volume (MPV) and platelet count; 5)
the influence of exercise training in other laboratorial parameters as lipids, blood
glucose and inflammatory activity; 6) finally, the primary endpoint of the study will be
evaluated in different prespecified subgroups such as diabetics, elderly, obese and
patients with chronic kidney disease.
2.1. Primary endpoint of the study: Evaluate the influence of regular supervised
exercise training for 3 months on platelet aggregability, analyzed by VerifyNowP2Y12®
test, in patients with recent AMI utilizing dual antiplatelet therapy.
2.2. Main secondary analyses:
A. Evaluate platelet aggregability immediately after acute exercise before and after the
exercise training period; for this propose, blood sample will be drawn immediately after
the first and second cardiopulmonary exercise testings, in trained and control groups.
B. Correlate the platelet aggregability level, evaluated by VerifyNowP2Y12®,
Multiplate-ADP®, Multiplate-ASPI®, with the level of MSNA.
2.3. Other exploratory analyses:
A. Evaluate the primary endpoint of the study utilizing Multiplate-ASPI® and
Multiplate-ADP®;
B. Evaluate the MPV in trained and control groups, and its correlation with platelet
aggregability;
C. Analyze, in trained and control groups, the following parameters:
Platelet count; LDL-cholesterol; HDL-cholesterol; Triglycerides; Lipid transference for
HDL; Fasting glucose; Glycated hemoglobin; C-reactive protein (CRP) ultrasensitive;
B-type natriuretic peptide (BNP); Troponin and Creatine Kinase MB-mass peak obtained
during hospitalization; Genetic polymorphisms; Heart rate variability and spontaneous
baroreflex control.
D. Analyze the primary endpoint within the following subgroups, taking into account the
parameters obtained during hospitalization:
Sex (male / female); ST segment elevation myocardial infarction (STEMI) or non-STEMI;
Basal heart rate (<70 or ≥ 70 bpm); History of arterial hypertension (presence or
absence); LDL levels (<100 or ≥ 100 mg/dL); Age ≥65 years and <65 years; Body Mass Index
<30 or ≥ 30 kg / m2; Creatinine clearance (MDRD) <60ml / min / m2 or ≥ 60 ml / min / m2;
Current or not smoking; History of diabetes (present or absent); HbA1c <6.5 or ≥ 6.5%;
GRACE risk score ≥140 and <140; Beta-blocker use.
3. Methodology:
This is a prospective, randomized study. Patients with stable AMI admitted to a Coronary Care
Unit, eligible to participate, will be randomized to a supervised exercise training program
for three months at a rehabilitation unit or to a control group not formally trained.
Patients who agree to participate will be included after the necessary explanations and the
signature of the informed consent form.
3.a. Sample size calculation: To perform the sample calculation, previously published data
wich showed platelet agreeability average of 32.9 ± 16 P2Y12 reactions units (PRU) in
post-AMI patients on ticagrelor was utilizes. For an expected 35% decrease in platelet
aggregability at trained group, and taking into account power of 80% and alpha index of 0.05,
including 31 patients in each group is required. Admitting a percentage of losses of 40%
given the difficulties inherent in the assessment of the sympathetic activity and adherence
to the training program, the initial plan contemplates the inclusion of 90 patients in the
study.
4. Study design: Prospective study in which eligible patients with uncomplicated AMI admitted
to a Coronary Care Unit will be randomized to performing a exercise training program by three
months or for an untrained control group, at a 1:1 or 1:2 rate, in order to adjust for more
frequent early follow-up interruptions in exercise training group. All patients included
after the necessary explanations and after signing the informed consent form. The patients
will be submitted to the collection of material for laboratory evaluation including platelet
aggregability tests, the assessment of a CPET in 01 and 04 months of the follow-up (end of
treatment). The MSNA will be performed at the end of followup.
