Tetracycline (Doxycycline) and Post Myocardial Infarction Remodeling (TIPTOP)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
David Antoniucci, Careggi Hospital
ClinicalTrials.gov Identifier:
NCT00469261
First received: May 3, 2007
Last updated: September 24, 2012
Last verified: September 2012
  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 2

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:


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 ]

Enrollment: 110
Study Start Date: May 2007
Study Completion Date: August 2011
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

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 by Careggi Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: David Antoniucci, MD, Careggi Hospital
ClinicalTrials.gov Identifier: NCT00469261     History of Changes
Other Study ID Numbers: TIP-TOP
Study First Received: May 3, 2007
Last Updated: September 24, 2012
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 April 23, 2014