Clinical trial NCT02562651: Changes in Myocardial Biomechanics and Early Short-term Doxycycline Therapy in Patients With Primary Anterior STEMI
Official title: Changes in Myocardial Biomechanics and Early Short-term Doxycycline Therapy in Patients With Acute Primary Anterior STEMI (ST Segment Elevation Myocardial Infarction)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Vascular Diseases
Cardiovascular Diseases
Acute Myocardial Infarction
Keywords: STEMI, adverse LVR (left ventricular remodeling), MMPs, Doxycycline
Lead sponsor: Russian Academy of Medical Sciences
Sponsor class: OTHER
First posted: 2015-09-29
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to investigate the changes of myocardial biomechanics and efficacy of doxycycline in patients with primary anterior STEMI.

Detailed description: It is known that MMPs (matrix metalloproteinases) take part in myocardial remodeling, which lead to the adverse remodeling of left ventricular. Doxycycline inhibiting MMPs and it help to prevent collagen degradation and following LV (left ventricular) dilatation. Some experimental studies on rat models have suggested an anti-remodeling effect of doxycycline in myocardial infarction by means of decrease in activity of MMPs-2 and recovery of contractile function of myocardium. The clinical trial was performed at 2013 (D.Antoniucci), but it was a single study and confirmed theoretical and experimental background.

The study is randomized, opened, controlled. 45 patients with the first anterior STEMI will be enrolled. On admission all patients will receive reperfusion therapy during the first 24 h. Patients will be randomized by the open envelope method and after that some of the participants will be on doxycycline (100 mg b.i.d. for 7 days) in addition to routine medical therapy for STEMI, but other will be on routine medical therapy of STEMI. After that they will have echocardiography at 3-d, 7-th, 14-th days and 6 month after STEMI. The investigators will evaluate left ventricular function of these patients by routine and speckle-tracking echocardiography, incidence of cardiovascular end points (death, recurrent myocardial infarction, angina, heart failure, stroke) and their combinations, also the investigators will take blood samples to assess metalloproteinases (MMPs) and other biomarkers.

Eligibility criteria: Inclusion Criteria:

* age ≥ 18 and ≤ 75 years at time of randomization (18 years and older)
* ST-elevation Q wave myocardial infarction
* term admission to an intensive care unit (ICU) in the first 24 hours of onset
* the reperfusion of the infarct-related coronary artery is not later than 24 hours after the initial onset of acute transmural myocardial infarction
* written the informed consent to participate in research

Exclusion Criteria:

* atrial fibrillation, a permanent form
* valvular heart disease
* severe comorbidity
* acute heart failure according to the Killip classification IV FC (functional class)
* history of chronic heart failure (NYHA III-IV)
* poor image quality for Echocardiography
* sinus bradycardia - heart rate of under 50 beats per minute, interventricular conduction delay (QRS \> 0,11 s.) and atrioventricular block II-III degree

Primary outcomes:
measure: Changes in LV end-diastolic volumes index, %
timeFrame: 14 days and 6 month after STEMI
Secondary outcomes:
measure: Incidence of cardiovascular death,%
timeFrame: 14 days and 6 month after STEMI
measure: Incidence of the recurrent myocardial infarction,%
timeFrame: 14 days and 6 month after STEMI
measure: Incidence of the angina,%
timeFrame: 14 days and 6 month after STEMI
measure: Incidence of the heart failure,%
timeFrame: 14 days and 6 month after STEMI
measure: Incidence of the stroke,%
timeFrame: 14 days and 6 month after STEMI
measure: Incidence of the combined endpoint,%
timeFrame: 14 days and 6 month after STEMI
measure: Incidence and severity of adverse events,%
timeFrame: 14 days and 6 month after STEMI
measure: Changes in 2 D global longitudinals strain,Δ %
timeFrame: 14 days and 6 month after STEMI
measure: Changes in MMPs and their inhibitors, other biomarkers, pg/ml
timeFrame: 14 days and 6 month after STEMI
Other outcomes:
Locations:
city: Tomsk
country: Russian Federation
facility: Research Institutite for Cardiology
state: Tomskii region
Study officials:
affiliation: Research Institute for Cardiology
name: Vyacheslav Ryabov, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: