Tetracycline (Doxycycline) and Post Myocardial Infarction Remodeling

Myocardial Infarction Clinical Trial

— TIPTOP  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00469261
• Other study ID #: TIP-TOP
• Status: Completed
• Phase: Phase 2
• First received: May 3, 2007
• Last updated: September 24, 2012
• Start date: May 2007
• Est. completion date: August 2011

Study information

• Verified date: September 2012
• Source: Careggi Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infarction
• Left Ventricular Remodeling
• Myocardial Infarction
• Ventricular Remodeling

Intervention

Drug:
• Doxycycline
Doxycycline 100 mg bid for seven days after enrollment
• Current medical therapy for AMI
Current medical therapy for AMI

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Careggi Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Evaluation of the time course of MMPs and their inhibitors in relation to left ventricular remodeling		6 months	No