Tetracycline (Doxycycline) and Post Myocardial Infarction Remodeling (TIPTOP)

Careggi Hospital

Status and phase: Completed; Phase 2

Conditions: Left Ventricular Remodeling; Myocardial Infarction

Treatments: Drug: Current medical therapy for AMI; Drug: Doxycycline

Study type: Interventional

Funder types: Other

Identifiers

NCT00469261

TIP-TOP

Details and patient eligibility

About

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.

Full 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.

Enrollment: 110 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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110 participants in 2 patient groups

Doxycycline

Experimental group

Description:

Active drug 100 mg bid for seven days in pts with AMI treated with Primary PCI and current medical therapy

Treatment:

Drug: Doxycycline

Standard Therapy

Active Comparator group

Description:

Pts with AMI treated with Primary PCI and current medical therapy

Treatment:

Drug: Current medical therapy for AMI