Protection of the Heart With Doxycycline During Coronary Artery Bypass Grafting

This study has been completed.
Sponsor:
Information provided by:
University of Alberta
ClinicalTrials.gov Identifier:
NCT00246740
First received: October 28, 2005
Last updated: January 11, 2010
Last verified: January 2010
  Purpose

The purpose of this study is to determine whether doxycycline(Periostat)at a sub-antimicrobial dose will decrease reperfusion injury after coronary artery bypass grafting (CABG) surgery with cardiopulmonary bypass (CPB).


Condition Intervention
Coronary Artery Bypass Grafting
Cardiopulmonary Bypass
Reperfusion Injury
Drug: Periostat

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Protection of the Heart With Doxycycline During Coronary Artery Bypass Grafting: A Pilot Study

Resource links provided by NLM:


Further study details as provided by University of Alberta:

Primary Outcome Measures:
  • Doxycycline, a tetracycline antibiotic that also possesses secondary inhibitory effects on matrix metalloproteinases (MMPs), will attenuate myocardial and systemic activation of MMPs if administered to patients prior to the onset of CPB. [ Time Frame: 2 days prior to surgery until 3 days post operative ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Attenuating the activation of MMPs will reduce cleavage of contractile protein regulatory elements such as troponin I (TnI) and myosin light chain 1 (MLC-1), which will improve cardiac functional recovery after CPB. [ Time Frame: 2 days prior to surgery until 3 days post operative ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: October 2005
Study Completion Date: May 2009
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Periostat
    In addition to standard care, patients will receive oral administration of 20 mg of doxycycline or placebo twice a day at least 2 days prior to surgery, on the day of surgery, and on postoperative days 1, 2, and 3.
Detailed Description:

This proposal is for a randomized, placebo-controlled, double-blinded study of the use of doxycycline in patients requiring CABG surgery. Patients will be randomized 1:1 to receive either doxycycline or placebo.

This study will be conducted in a blinded manner. The pharmacy will randomize patients and will have the randomization code. The code will only be broken in the case of an emergency and the event will be fully documented.

In addition to standard care, patients will receive oral administration of 20 mg of doxycycline or placebo twice a day at least 2 days prior to surgery, on the day of surgery, and on postoperative days 1, 2, and 3.

Myocardial atrial biopsies will be taken at 2 time points during the CABG procedure: during cannulation of the right atrium and 10 minutes after cross-clamp release. Tissue will be analyzed for MMP-2 and -9 activity and TnI and MLC-1 levels.

A Swan-Ganz-Catheter will be placed in the pulmonary artery over 24 hours to measure hemodynamics (LVSWI).

A coronary sinus catheter will be placed under echocardiographic guidance prior to initiation of CPB (will be removed 20 minutes after cross-clamp release).

Patients will have an additional ECG on post-operative days 1 and 3.

Additional blood will be drawn to determine doxycycline plasma levels, MMP-2 and -9 activity, total gelatinolytic activity, and levels of troponin I and T products at the following time points: pre-induction, prior to initiation of CPB, 10 and 20 minutes following the release of the aortic cross clamp (arterial and venous) and 3, 6, 24 and 72 hours post aortic cross clamp removal (venous). Each of the above samples will require 6 mL of blood for a study total of 72 mL. At the time of each blood draw we will measure and record the hematocrit value.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • Aged 18 through 80 years, inclusive
  • Scheduled for primary CABG surgery with CPB

Exclusion Criteria:

  • Females of childbearing potential
  • Emergency CABG
  • Previous sternotomy
  • Planned simultaneous surgery (i.e. valve repair or carotid endarterectomy)
  • Myocardial infarction within 48 hours
  • Pre-operative atrial fibrillation
  • Pre-operative ventricular pacing or left bundle branch block (LBBB)
  • Known hypersensitivity to tetracycline class antibiotics
  • Renal failure requiring dialysis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00246740

Locations
Canada, Alberta
University of Alberta Hospital
Edmonton, Alberta, Canada, T6G 2G3
Sponsors and Collaborators
University of Alberta
Investigators
Principal Investigator: Barry A Finegan, MB, FFARS(I), FRCPC Department of Anesthesiology and Pain Medicine, University of Alberta Hospital
  More Information

No publications provided

Responsible Party: Dr. Barry Finegan, University of Alberta
ClinicalTrials.gov Identifier: NCT00246740     History of Changes
Other Study ID Numbers: Protect Study Protocol
Study First Received: October 28, 2005
Last Updated: January 11, 2010
Health Authority: Canada: Health Canada

Keywords provided by University of Alberta:
Doxycycline
coronary artery bypass grafting

Additional relevant MeSH terms:
Reperfusion Injury
Wounds and Injuries
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications
Pathologic Processes
Doxycycline
Doxycycline hyclate
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on July 26, 2014