Clinical trial NCT00469261: Tetracycline (Doxycycline) and Post Myocardial Infarction Remodeling
Official title: Tetracycline (Doxycycline) In Patients With Large Acute Myocardial Infarction TO Prevent Left Ventricular Remodeling. TIPTOP Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myocardial Infarction
Left Ventricular Remodeling
Keywords: Myocardial infarction
Ventricular remodeling
Matrix metalloproteinases
Doxycycline
Lead sponsor: Careggi Hospital
Sponsor class: OTHER
First posted: 2007-05-04
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: 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
timeFrame: 6 months
Secondary outcomes:
measure: Evaluation of the time course of MMPs and their inhibitors in relation to left ventricular remodeling
timeFrame: 6 months
Other outcomes:
Locations:
Study officials:
affiliation: Careggi Hospital, Florence, Italy
name: Giampaolo Cerisano, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Careggi Hospital, Florence, Italy
name: David Antoniucci, MD
role: STUDY_DIRECTOR
affiliation: Careggi Hospital, Florence, Italy
name: Piergiovanni Buonamici, MD
role: STUDY_CHAIR
affiliation: Careggi Hospital, Florence, Italy
name: Emilio V Dovellini, MD
role: STUDY_CHAIR
affiliation: Careggi Hospital, Florence, Italy
name: Alberto Santini, MD
role: STUDY_CHAIR
affiliation: Careggi Hospital, Florence, Italy
name: Umberto Signorini, MD
role: STUDY_CHAIR
affiliation: Careggi Hospital, Florence, Italy
name: Nazario Carrabba, MD
role: STUDY_CHAIR
affiliation: Careggi Hospital, Florence, Italy
name: Paolo D Pucci, MD
role: STUDY_CHAIR
affiliation: Careggi Hospital , Florence, Italy
name: Renato Valenti, MD
role: STUDY_CHAIR
References:
citation: 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.