TIPTOP: Tetracycline (Doxycycline) and Post Myocardial Infarction Remodeling
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Doxycycline Active drug 100 mg bid for seven days in pts with AMI treated with Primary PCI and current medical therapy |
Drug: Doxycycline
Doxycycline 100 mg bid for seven days after enrollment
|
| Active Comparator: Standard Therapy Pts with AMI treated with Primary PCI and current medical therapy |
Drug: Current medical therapy for AMI
Current medical therapy for AMI
|
Outcome Measures
Primary Outcome 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 [6 months]
Secondary Outcome Measures
- Evaluation of the time course of MMPs and their inhibitors in relation to left ventricular remodeling [6 months]
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Careggi Hospital
Investigators
- Principal Investigator: Giampaolo Cerisano, MD, Careggi Hospital, Florence, Italy
- Study Director: David Antoniucci, MD, Careggi Hospital, Florence, Italy
- Study Chair: Piergiovanni Buonamici, MD, Careggi Hospital, Florence, Italy
- Study Chair: Emilio V Dovellini, MD, Careggi Hospital, Florence, Italy
- Study Chair: Alberto Santini, MD, Careggi Hospital, Florence, Italy
- Study Chair: Umberto Signorini, MD, Careggi Hospital, Florence, Italy
- Study Chair: Nazario Carrabba, MD, Careggi Hospital, Florence, Italy
- Study Chair: Paolo D Pucci, MD, Careggi Hospital, Florence, Italy
- Study Chair: Renato Valenti, MD, Careggi Hospital , Florence, Italy
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TIP-TOP