Tetracycline (Doxycycline) and Post Myocardial Infarction Remodeling

Study Overview
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Brief Summary
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The aim of the study is to assess the efficacy of an antibiotic treatment with tetracycline (doxycycline) in the early stage of large reperfused acute myocardial infarction (AMI), in preventing left ventricular (LV) remodeling.

Detailed Description
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A myocardial interstitial matrix, that provides structural support and integrity to the myocardium, is a key element to determine post infarction left ventricular remodeling (LVR). The metalloproteinases (MMPs), an enzymatic system secreted in the extracellular medium by macrophages, has been shown to be able to degrade the most important extracellular matrix components. Various animal experimental models have demonstrated that MMP specific inhibition in the first phase of myocardial infarction is able to contrast LVR. Doxycycline, a member of the tetracyclines, has been shown to block various inflammation mediators and to attenuate MMP-2 and MMP-9 expression and activity at a sub-antimicrobial dosage. Some experimental studies on rat models have suggested an anti-remodeling effect of doxycycline in myocardial infarction. In the present study we want to evaluate if a treatment with doxycycline (100 mg b.i.d.) in the first seven days after a reperfused large (ejection fraction less than 40%) acute myocardial infarction, is effective in preventing six-month LVR.

Official Title
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Tetracycline (Doxycycline) In Patients With Large Acute Myocardial Infarction TO Prevent Left Ventricular Remodeling. TIPTOP Study

Conditions
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Myocardial Infarction, Left Ventricular Remodeling

Intervention / Treatment
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* Drug: Doxycycline
* Drug: Current medical therapy for AMI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute myocardial infarction Left ventricular ejection fraction less than 40% Exclusion Criteria: No written consensus Allergy to tetracycline Mechanical complication of AMI Previous myocardial infarction Valvular and/or myocardiopathy known or suspected Renal failure (creatinine above 2 mg/dL) Connective tissue disease Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Doxycycline<br>Active drug 100 mg bid for seven days in pts with AMI treated with Primary PCI and current medical therapy | Drug: Doxycycline<br>* Doxycycline 100 mg bid for seven days after enrollment<br>|
| Active Comparator: Standard Therapy<br>Pts with AMI treated with Primary PCI and current medical therapy | Drug: Current medical therapy for AMI<br>* Current medical therapy for AMI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of LV dilation (six months versus baseline LV end-diastolic volume index by 2D-echocardiogram [echo]) more than 50% in the treated group in comparison to the placebo group |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the time course of MMPs and their inhibitors in relation to left ventricular remodeling |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Doxycycline, Myocardial infarction, Ventricular remodeling, Matrix metalloproteinases