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Myocardial Infarction, AcutePhase 4CONTRAST-2NCT04347434

Assessment of the Effects of Long-term Lipid-lowering Therapy in Patients With Primary STEMI or NSTEMI

A Phase 4 study testing Atorvastatin 80mg in people with Myocardial Infarction, Acute and Myocardial Strain, run by Penza State University at 1 site in Russia.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

In a single-center, open-label, prospective, controlled, clinical study, it is planned to include 300 patients hospitalized in the cardiology department of SBHI Penza regional clinical hospital n.a. N.N. Burdenko. Read more about this study

Who is it for?
Ages 30 to 70 years
What is being tested?
Atorvastatin 80mg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
300 participants
Where
1 siteRussia
Study dates
12 Feb 2020to 30 Dec 2027
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 1. Signed Informed Consent Form 2 Primary STEMI or NSTEMI confirmed by ECG, troponin I and CPK-MB levels, coronary angiography.
  • 3. Presence of an infarct-related artery according to coronary angiography.

Who cannot join

  • Presence of hemodynamically relevant stenosis exceeding 30% in several coronary arteries confirmed by CAG;
  • Recurrent or repeated myocardial infarction.
  • Exogenous hypertriglyceridemia (type 1 hyperchilomicronemia).
  • The development of acute heart failure III-IV prior to randomization
  • Individual intolerance to statins, ezetimibe.
  • Congenital and acquired heart diseases.
Show all 21Show fewer
  • Severe concomitant diseases in the stage of decompensation.
  • Non-sinus rhythm, established artificial pacemaker.
  • Sinoatrial and atrioventricular blockade of 2-3 degrees.
  • QRS complex exceeding 100 ms.
  • The presence of severe LV hypertrophy according to echocardiography.
  • Uncontrolled hypertension with SBP> 180 mm Hg and DBP> 110 mmHg
  • Diabetes mellitus (DM) type 1 and 2.
  • Current existence of severe anemia (Hb < 100 g/L)
  • Chronic kidney disease (creatinine clearance less than 30 ml / min / 1.73 m2 according to the CKD-EPI).
  • Non-corrected thyroid dysfunction with hyper / hypothyroidism.
  • Body mass index (BMI) ≥35 kg / m2.
  • Pregnancy, lactation.
  • Alcohol abuse, drug addiction.
  • Other serious concomitant diseases that exclude the possibility of study participation.
  • Participation in other clinical trials within the last two months.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Nadezhda V Burko, PhD contact

+78412548229

hopeful.n@mail.ru

Russia1 site, 1 recruiting
  • Valentin Oleynikov

    Penza, 440026

    Valentin Oleynikov, Prof., +78412548229, v.oleynikof@gmail.com

    Nadezhda Burko, PhD, +78412548229, hopeful.n@mail.ru

    Recruiting

Other trials in Russia

About this study

Official title: Assessment of the Effects of Long-term Lipid-lowering Therapy on Parameters of Electrical Myocardial Heterogeneity, Myocardial Deformation Characteristics, Vascular Rigidity, and Quality of Life in Patients With Primary STEMI or NSTEMI

In a single-center, open-label, prospective, controlled, clinical study, it is planned to include 300 patients hospitalized in the cardiology department of SBHI Penza regional clinical hospital n.a. N.N. Burdenko. Recruitment of patients will be carried out at the Department of Therapy of the Medical Institute of the Penza State University. Patients meeting the inclusion criteria and not meeting the exclusion criteria will be included in the study.

Initially, lipid-lowering treatment with atorvastatin is prescribed at a dose of 80 mg / day from the first 24-96 hours of AMI in addition to the standard therapy.

Read more

If there is no achievement of the target level of LDL-C, ≤1.5 mmol / L after 5-6 weeks from the AMI onset, patients additionally receive ezetimibe at a dose of 10 mg 1 time / day.

Standard AMI treatment includes dual antiplatelet therapy, ACE inhibitors, beta-blockers (if indicated). Prescription of proton pump inhibitors and nitrates is possible (if indicated).

The total follow-up is 96 weeks. Prescreening - 600 people; screening and randomization - 300 people. Parameters of electrical myocardial heterogeneity, myocardial deformation characteristics, vascular rigidity, and quality of life will be assessed according to the study plan.

Read the detailed description

Methods

  1. Blood chemistry test. Total cholesterol, LDL, HDL, triglycerides, AST, ALT, CPK, glucose, CRP, creatinine, glycosylated hemoglobin
  2. 2D and 3D transthoracic echocardiography (Vivid GE 95 Healthcare (USA). 3D speckle echocardiography (3DSTE) for a detailed study of the phase-by-phase movement and spatial interaction of all muscle layers of the left ventricle in different phases of the cardiac cycle to obtain quantitative values of the deformation of the left ventricle individual segments in the longitudinal, circumferential and radial directions. The analysis of standard indicators of echocardiography: biplane ejection fraction according to the Simpson method, 3D ejection fraction, EDV (end-diastolic volume), ESV (end-systolic volume) and their indices. The left ventricular myocardial mass index (LVMI). Using a tissue doppler, the parameters characterizing the diastolic function are recorded: the LA volume, the early diastolic velocity of the mitral valve fibrous ring, the ratio of the early diastolic transmitral flow E to the average early diastolic speed of the fibrous ring e´, and the maximum tricuspid regurgitation rate. Myocardial strain is analyzed using specialized software - EchoPac Software Only (General Electric Co., 2018). For three-dimensional strain analysis, the left ventricle is automatically divided into 17 segments using standard segmentation schemes. The software allows obtaining strain values in the endocardial, middle and epicardial layers of the myocardium. Over a period of time, indicators for each segment are automatically calculated: longitudinal strain/strain rate (LS,%/LSR, cm / s-1), circumferential strain/strain rate (CS,%/CSR, cm / s-1), radial strain/strain rate(RS,%/RSR, cm / s-1), area strain), rotation, rotation along the axis of the left ventricle (Torsion).
  3. Long-term ECG monitoring over 3 leads with an assessment of the parameters of myocardial electrical instability A long-term ECG recording (120 hours) in patients with myocardial infarction will be performed using the Astrocard ECG system (CJSC Meditek, Russia) with 3-channel recorders. Long-term recordings will be analyzed separately for 3 time intervals: 24, 72 and 120 hours. Pauses of rhythm, rhythm disturbances - extrasystole, unstable tachycardia, AF paroxysm and atrial flutter, ventricular fibrillation, conduction disturbance will be recorded. Assessment of the ST segment dynamics will be carried out with detection of ischemia episodes, which will be detected when the ST segment is displaced ≥10 mV from the baseline 80 ms after the J point for at least 1 min - episodes of elevation and depression of the ST segment. According to the long-term ECG monitoring recordings, the following parameters will be analyzed (separately for 3 intervals - 24, 72 and 120 hours): circadian dynamics of heart rate; late ventricular potentials (LVP); variance and duration of the QT interval; heart rate variability (HRV); heart rate turbulence (TCP); chronotropic load (CL). Circadian dynamics of heart rate. The circadian dynamics of heart rate will be analyzed with an estimate of the minimum, average and maximum heart rate per day, during waking hours and night sleep. The circadian index (CI) will be defined as the ratio of the average heart rate in the daytime and the average heart rate in the night. LVP. The LVP will be evaluated in the standard averaging mode in the range of 40-100 Hz by the noise level not exceeding 0.9 μV. Records of the 24-h ECG in patients who have a decrease in intraventricular conduction, bundle branches blockade, will not be subjected to LVP analysis. An automatic analysis of late post-depolarization begins with a search for the QRS reference complex, which will be used later as a reference for averaging. Subsequently, the ECG signal will be processed programmatically by the time analysis method, at the end of which the following parameters will be evaluated: the width of the filtered QRS complex (QRSf), the duration of the low-amplitude potentials at the end of the QRS complex of the final part of the complex (HFLA), the rms value of the last 40 ms QRS (RMS ) Dispersion and QT interval duration. For a detailed study of the repolarization process in the analysis of records, close attention will be paid to the analysis of the duration, variability and variance of the QT interval. HRV. The following HRV time indicators will be considered:
  • Mean NN (ms) - average value of all RR-intervals;
  • SDNN (ms) - standard deviation of the average values of RR-intervals;
  • SDNNi (ms) - average value of standard deviations RR for 5-minute recording periods;
  • SDANN (ms) is the standard deviation of the mean values of the sinus intervals RR for 5 min;
  • rMSSD (ms) is the square root of the sum of the differences of subsequent RR intervals;
  • pNN50 (%) is the percentage of successive RR intervals differing by more than 50 ms;
  • HRVti - triangular index;
  • TINN is the index of triangular interpolation of the histogram of RR-intervals. HRV frequency parameters:
  • TotP (ms2) is the power of the total spectrum;
  • ULfP (ms2) - spectrum power in the ultralow frequency range;
  • VLfP (ms2) is the power of the spectrum within very low frequencies;
  • LfP (ms2) - low-frequency range of frequencies; HfP (ms2) - high-frequency component of HRV; L / H - an indicator of the balance of the vagosympathetic balance. Evaluation of the above HRV parameters will be carried out per day, night and day hours. TCP is characterized by two independent parameters - the beginning of turbulence (TO) and the slope of turbulence (TS). Heart CL is assessed by the level and duration of exceeding the actual (observed in the patient during monitoring) heart rate values of the threshold heart rate calculated individually according to the proposed formulas with differentiation for periods of wakefulness and night sleep: THR-W (bpm) = HRmax (bpm) × 0.45, where THR-W is the threshold value of the heart rate during wakeful hours in beats per minute, heart rate max is the age-appropriate value of the maximum possible heart rate in beats per minute, 0.45 is the coefficient of the threshold level of heart rate; THR-S (bpm) = THR-W (bpm): 1.24, where THR-S (bpm) is the threshold value of the heart rate during the night's sleep.
  1. Ultrasound of the common carotid arteries with RF high frequency signal technology The study of local vascular stiffness by high-frequency RF signal technology using ultrasound of the common carotid arteries (CCA) will be carried out in B mode using MyLab 90 (Esaote, Italy). The RF signal technology includes two programs: RF-QIMT and RF-QAS. The following CCA indicators are analyzed: IMT - intima-media thickness, loc Psys - local systolic pressure in the carotid artery, loc Pdia - local diastolic pressure, P (T1) - pressure at the local point, stiffness indices β and α, DC is the coefficient of lateral distensibility, CC - coefficient of lateral compliance, Aix is the augmentation index, AP is the amplification pressure, PWV is the local pulse wave velocity in the carotid artery.
  2. Ultrasound of the brachiocephalic and femoral arteries The brachiocephalic and femoral arteries will be scanned using a Vivid GE 95 ultrasound scanner (Healthcare, USA) using a linear sensor in B-mode, spectral Doppler imaging and color Doppler imaging. Quantitative analysis of atherosclerotic plaque includes determining the extent and degree of narrowing of the lumen of the vessel (percentage of stenosis) by the cross-sectional area (Sa) of the vessel: Sa = (A1 - A2) × 100% / A1, where A1 is the true cross-sectional area of the vessel, A2 is the passable cross-sectional area of the vessel.
  3. Applanation tonometry. SphygmoCor apparatus (AtCor Medical, Australia) uses pulsed wave to calculate the characteristics of central pressure in aorta. The applanation tonometry technique includes two programs: PWA and PWV. The first allows to record central aortic pressure indicators: systolic aortic pressure - SBPao, diastolic - DBPao, pulse - PPao, mean hemodynamic - MBPao based on registration of the radial artery PWV. Using the PWV program, sequential recording of PWV from the common carotid and femoral arteries simultaneously with the ECG channel analyzes the PWV in the aorta (cfPWV).
  4. Volume sphygmography. The measurements will be carried out with the VS-1000 device (Fukuda Denshi, Japan) while simultaneously recording plethysmograms on four limbs (using cuffs), ECG, phonocardiogram, and PWV on the carotid and femoral arteries. PWV is evaluated in different parts of the circulatory system (i.e., aorta (PWV), predominantly elastic arteries (R/L-PWV) and predominantly muscular arteries (B-PWV)). Cardio-Ankle Vascular Index (CAVI) is determined - an indicator that reflects the true stiffness of the vascular wall. CAVI is calculated by registering PWV at two points and measuring SBP and DBP. Additionally augmentation index and biological age will be calculated automatically.
  5. Flow-mediated dilation. Endothelial function is evaluated by ultrasonic determination of flow-mediated dilation (FMD) during the postocclusive reactive hyperemia test using the method described by D. Celenmajer et. al.
  6. Six-minute walk (6MW) test. The patient should not take cardiological drugs and should not smoke within at least 2 hours before the test. Before the 6MW test, the patient should have a 10-minute quiet rest in a sitting position. During this rest period, the following text should be read to the patient: "You will have to walk for 6 minutes, without using continuous running or alternate running and walking, with the aim to cover a maximum distance. You will walk back and forth along the corridor. You can slow down the pace, stop and have a rest in case of dyspnea or weakness. You can lean against the wall during rest. Then, you will have to resume the walk. Remember that your aim is to cover maximum distance in 6 minutes." At the 6-minute time point, the patient should be asked to stop and stand still until the covered distance has been measured.
  7. Computer Pulse Oximetry. During the 6-minute walk test, computer pulse oximetry is planned on a PulseOx 7500 instrument (SPO medical, Israel) to study saturation dynamics in comparison groups.
  8. Treatment compliance will be evaluated by standard methods (counting the remaining tablets). Morisky-Green Questionnaire
  9. Quality of Life Assessment. The following questionnaires are planned to be completed: Seattle Angina Questionnaire (SAQ), Minnesota Questionnaire, Clinical Assessment Scale for CHF (MQCAS) (modified by Mareev VY, 2000), analog-visual scale.
  10. Assessment of physical activity. It is planned to fill out a questionnaire for assessing the level of physical activity and a short international questionnaire for determining the physical activity of the International Questionnaire On Physical Activity - IPAQ
  11. Assessment of Anxiety Depression. An analysis of anxiety and depressive disorders in patients using the hospital scale of anxiety and depression (HADS) is planned
Being tested
Atorvastatin 80mg
Keywords
STEMI, NSTEMI, myocardial strain,, arterial stiffness,, lipid-lowering therapy,, electrical myocardial heterogeneity
Medical subject headings
Myocardial Infarction, ST Elevation Myocardial Infarction, Non-ST Elevated Myocardial Infarction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Atorvastatin 80mgDrug

    Also called Ezetimibe

    Atorvastatin is prescribed at a dose of 80 mg / day from the first 24-96 hours of AMI in addition to the standard therapy

Study groups in NCT04347434
Study groupRoleWhat they receive
Atorvastatin 80 mgExperimentalTreatment with atorvastatin is prescribed at a dose of 80 mg / day from the first 24-96 hours of AMI in addition to the standard therapy. If there is no achievement of the target level of LDL-C, ≤1.5 mmol / L after 5-6 weeks from the AMI onset, patients additionally receive ezetimibe at a dose of 10 mg 1 time / day.
Receives: Drug: Atorvastatin 80mg
Atorvastatin-EzetimibeActive comparatorIn the absence of reaching the target level of LDL-C of ≤1.4 mmol / L and a decrease in the indicator by ≥50% after 5-6 weeks from the onset of AMI, patients additionally receive ezetimibe at a dose of 10 mg 1 time / day.
Receives: Drug: Atorvastatin 80mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Ventricular arrhythmias

    Statistically significant differences in the frequency of ventricular arrhythmias as compared to controls

    Measured: up to 48 months

  2. Systolic function

    Statistically significant differences in systolic function of the left ventricle according to transthoracic echocardiography as compared to controls;

    Measured: up to 48 months

  3. Myocardial deformation of the LA and LV

    Statistically significant differences in the myocardial deformation of the LA and LV as compared to controls

    Measured: up to 48 months

  4. PCI / CABG for a new case of coronary atherosclerosis, hospitalization for unstable angina

    Statistically significant differences for major coronary events - PCI / CABG for a new case of coronary atherosclerosis, hospitalization for unstable angina as compared to controls

    Measured: up to 48 months

  5. Myocardial electrical instability

    Statistically significant differences in the late ventricular potentials, heart rate variability, QT interval dispersion (ms) as compared to controls

    Measured: up to 120 hours for 2 years period

  6. Heart rate turbulence

    Statistically significant differences in the parameters of heart rate turbulence (%) as compared to controls

    Measured: up to 120 hours for 2 years period

Secondary outcomes (15)
  1. Cardiovascular mortality

    Statistically significant differences for incidence of CV events as compared to controls

    Measured: up to 48 months

  2. Frequency of repeated fatal / non-fatal MI

    Statistically significant differences in the frequency of repeated fatal / non-fatal MI as compared to controls

    Measured: up to 48 months

  3. Hospitalization due to acute decompensation of heart failure

    Statistically significant differences according to the frequency of hospitalization due to acute decompensation of heart failure as compared to controls

    Measured: up to 48 months

  4. Structural state of arteries different types

    Statistically significant differences in pulse wave velocities in arteries of various calibers, as compared to controls

    Measured: up to 48 months

  5. Structural state of carotid artery

    Statistically significant differences in intima-media thickness of carotid artery according ultrasound, as compared to controls

    Measured: up to 48 months

  6. Functional state of arteries

    Statistically significant differences in flow-mediated dilation parameters (diameter of brachial artery, mm) assessed by ultrasound, as compared to controls

    Measured: up to 48 months

  7. Progression of CHF, exercise tolerance

    Statistically significant differences in 6-minute walk test (distance covered, m), as compared to controls

    Measured: up to 48 months

  8. Progression of CHF, laboratory data

    Statistically significant differences in BNP level (pg/ml), as compared to controls

    Measured: up to 48 months

  9. Left ventricular remodeling

    Statistically significant differences echocardiographic parameters of left ventricle pathological remodeling (ejection fraction, %, EDVi, ESVi) as compared to controls

    Measured: up to 48 months

  10. Lipid profile

    Statistically significant differences of lipid profile (mmol/l) as compared to controls

    Measured: up to 48 months

  11. Laboratory parameters

    Statistically significant differences of CRP (mg/l) as compared to controls

    Measured: up to 48 months

  12. Angina episodes

    Statistically significant differences on angina episodes assessed by Seattle Angina Questionnaire (min - 19, max - 108 better outcome), as compared to controls

    Measured: up to 48 months

  13. Quality of life questionnaire

    Statistically significant differences according to the quality of life of patients assessed by Minnesota Questionnaire (min -0, max-105, worse outcome), as compared to controls

    Measured: up to 48 months

  14. Quality of life questionnaire in СHF

    Statistically significant differences according to the quality of life of patients assessed by Clinical Assessment Scale for CHF(min -0, max-20, worse outcome), as compared to controls

    Measured: up to 48 months

  15. Patients wellbeing

    Statistically significant differences of patients wellbeing according to the analog-visual scale , as compared to controls

    Measured: up to 48 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Apr 2020
  2. Study start12 Feb 2020
  3. Primary completion12 Nov 2027 (estimated)
  4. Study completion30 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Model description
Initially, hypolipidemic treatment with atorvastatin at a dose of 80 mg / day is prescribed from the first 24-96 hours of AMI in addition to standard therapy for the disease.
Masking
None (open label)
Enrolment
300 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04347434
Sponsor's protocol ID
PSU/T-471
Acronym
CONTRAST-2
Status last verified
Nov 2023
First submitted
20 Mar 2020
Last updated
24 Nov 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Oleynikov V, Salyamova L, Vdovkin A, Donetskaya N, Avdeeva I, Babkina I, Averyanova E. The Role of the Extracellular Volume of the Infarction Zone and the Remote Myocardium in Predicting Systolic Dysfunction After the First Myocardial Infarction. Diagnostics (Basel). 2026 Aug 20;16(16):2663. doi: 10.3390/diagnostics16162663.

    PubMed 42651065

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Atorvastatin 80mg in people with Myocardial Infarction, Acute and Myocardial Strain, run by Penza State University at 1 site in Russia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 24 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Nadezhda V Burko, PhD (+78412548229, hopeful.n@mail.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ventricular arrhythmias (time frame: up to 48 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04347434, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2023.

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