Tetracycline (Doxycycline) and Post Myocardial Infarction Remodeling - Full Text View

Sponsor:	Careggi Hospital
Information provided by:	Careggi Hospital
ClinicalTrials.gov Identifier:	NCT00469261

Purpose

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	Intervention	Phase
Myocardial Infarction Left Ventricular Remodeling	Drug: Doxycycline Drug: Current medical therapy for AMI	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Tetracycline (Doxycycline) In Patients With Large Acute Myocardial Infarction TO Prevent Left Ventricular Remodeling. TIPTOP Study

Resource links provided by NLM:

MedlinePlus related topics: Heart Attack

Drug Information available for: Tetracycline Tetracycline hydrochloride Doxycycline Doxycycline hyclate Doxycycline calcium

U.S. FDA Resources

Further study details as provided by Careggi Hospital:

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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Evaluation of the time course of MMPs and their inhibitors in relation to left ventricular remodeling [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	110
Study Start Date:	May 2007
Estimated Study Completion Date:	August 2011
Estimated Primary Completion Date:	August 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00469261

Locations

Italy
Careggi Hospital, Department of Heart and Vessels
Florence, Italy, 50100

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

More Information

No publications provided

Responsible Party:	Giampaolo Cerisano, MD, Careggi Hospital
ClinicalTrials.gov Identifier:	NCT00469261 History of Changes
Other Study ID Numbers:	arcard2007/002
Study First Received:	May 3, 2007
Last Updated:	February 10, 2011
Health Authority:	Italy: Ministry of Health

Keywords provided by Careggi Hospital:

Myocardial infarction
Ventricular remodeling
Matrix metalloproteinases
Doxycycline

Additional relevant MeSH terms:

Infarction
Myocardial Infarction
Ventricular Remodeling
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Pathological Conditions, Anatomical
Tetracycline

Doxycycline
Doxycycline hyclate
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on February 12, 2012