Tetracycline (Doxycycline) and Post Myocardial Infarction Remodeling

Phase 2

Completed

• Conditions: Left Ventricular Remodeling; Myocardial Infarction
• Interventions: Drug: Current medical therapy for AMI; Drug: Doxycycline

• Registration Number: NCT00469261
• Lead Sponsor: Careggi Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2007-05
• Study First Submitted: 2007-05-03
• Study First Submitted QC: 2007-05-03
• Study First Posted: 2007-05-04
• Primary Completion: 2011-08
• Study Completion: 2011-08
• Status Verified: 2012-09
• Last Update Submitted: 2012-09-24
• Last Update Posted: 2012-09-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 110

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard Therapy	Current medical therapy for AMI	Pts with AMI treated with Primary PCI and current medical therapy
Doxycycline	Doxycycline	Active drug 100 mg bid for seven days in pts with AMI treated with Primary PCI and current medical therapy

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Evaluation of the time course of MMPs and their inhibitors in relation to left ventricular remodeling	6 months