Changes in Myocardial Biomechanics and Early Short-term Doxycycline Therapy in Patients With Primary Anterior STEMI (MASTARD)

Changes in Myocardial Biomechanics and Early Short-term Doxycycline Therapy in Patients With Acute Primary Anterior STEMI (ST Segment Elevation Myocardial Infarction)

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

Study Overview

• Status: Unknown
• Conditions: Cardiovascular Diseases; Vascular Diseases; Acute Myocardial Infarction
• Intervention / Treatment: Drug: Doxycycline; Other: Standard care for 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.

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Tomskii region
    • Tomsk, Tomskii region, Russian Federation, 634012
      • Research Institutite for Cardiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doxycycline; 100 mg of Doxycycline bid for seven days in pts with STEMI underwent PCI (percutaneous coronary intervention) and with current medical therapy	Drug: Doxycycline; Doxycycline bid for the first 7 days after primary anterior STEMI; Other Names: Doxycycline Solutab
Active Comparator: Active comparator; Standard care for STEMI	Other: Standard care for STEMI; Invasive and medical treatment for STEMI according to guidelines; Other Names: Invasive and medical treatment for STEMI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in LV end-diastolic volumes index, %	14 days and 6 month after STEMI

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of cardiovascular death,%	14 days and 6 month after STEMI
Incidence of the recurrent myocardial infarction,%	14 days and 6 month after STEMI
Incidence of the angina,%	14 days and 6 month after STEMI
Incidence of the heart failure,%	14 days and 6 month after STEMI
Incidence of the stroke,%	14 days and 6 month after STEMI
Incidence of the combined endpoint,%	14 days and 6 month after STEMI
Incidence and severity of adverse events,%	14 days and 6 month after STEMI
Changes in 2 D global longitudinals strain,Δ %	14 days and 6 month after STEMI
Changes in MMPs and their inhibitors, other biomarkers, pg/ml	14 days and 6 month after STEMI

Collaborators and Investigators

• Sponsor: Russian Academy of Medical Sciences
• Investigators: Principal Investigator: Vyacheslav Ryabov, MD,PhD, Research Institute for Cardiology

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Anticipated): February 1, 2017
• Study Completion (Anticipated): June 1, 2017

Study Registration Dates

• First Submitted: July 26, 2015
• First Submitted That Met QC Criteria: September 25, 2015
• First Posted (Estimate): September 29, 2015

Study Record Updates

• Last Update Posted (Estimate): December 13, 2016
• Last Update Submitted That Met QC Criteria: December 10, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: STEMI, adverse LVR (left ventricular remodeling), MMPs, Doxycycline
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Myocardial Infarction; Infarction; Cardiovascular Diseases; Vascular Diseases; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: 1202