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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Doxycycline | Experimental | Active drug 100 mg bid for seven days in pts with AMI treated with Primary PCI and current medical therapy |
|
| Standard Therapy | Active Comparator | Pts with AMI treated with Primary PCI and current medical therapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Doxycycline | Drug | Doxycycline 100 mg bid for seven days after enrollment |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of the time course of MMPs and their inhibitors in relation to left ventricular remodeling | 6 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Giampaolo Cerisano, MD | Careggi Hospital, Florence, Italy | Principal Investigator |
| David Antoniucci, MD | Careggi Hospital, Florence, Italy | Study Director |
| 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 Chair |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24104875 | Derived | Cerisano G, Buonamici P, Valenti R, Sciagra R, Raspanti S, Santini A, Carrabba N, Dovellini EV, Romito R, Pupi A, Colonna P, Antoniucci D. Early short-term doxycycline therapy in patients with acute myocardial infarction and left ventricular dysfunction to prevent the ominous progression to adverse remodelling: the TIPTOP trial. Eur Heart J. 2014 Jan;35(3):184-91. doi: 10.1093/eurheartj/eht420. Epub 2013 Oct 8. |
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| ID | Term |
|---|---|
| D009203 | Myocardial Infarction |
| D020257 | Ventricular Remodeling |
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D004318 | Doxycycline |
| ID | Term |
|---|---|
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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| Current medical therapy for AMI |
| Drug |
Current medical therapy for AMI |
|
| D007238 |
| Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |
| D020763 | Pathological Conditions, Anatomical |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |