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

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Placebo Control, Parallel Assignment, Efficacy Study

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.

Intervention(s) in this Clinical Trial

• Drug: Doxycycline

Primary Measures

• 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
  • Time Frame: 6 months
    

Secondary Measures

• Evaluation of the time course of MMPs and their inhibitors in relation to left ventricular remodeling
  • Time Frame: 6 months
    

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Careggi Hospital

Overall Clinical Trial Officials and Contacts

Giampaolo Cerisano, MD Principal Investigator Careggi Hospital, Florence, Italy  

Overall Contact: Piergiovanni Buonamici, MD +39-055-410752 carddept@tin.it

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00469261

Study ID Number: arcard2007/002

ClinicalTrials.gov Identifier: NCT00469261

Health Authority: Italy: Ministry of Health