Protection of the Heart With Doxycycline During Coronary Artery Bypass Grafting - Tabular View

Tracking Information

First Received Date ^ICMJE

October 28, 2005

Last Updated Date

November 18, 2008

Start Date ^ICMJE

October 2005

Primary Completion Date

May 2008 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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 ]

Original Primary Outcome Measures ^ICMJE

Doxycycline, also possessing secondary inhibitory effects on matrix metalloproteinases (MMPs), will attenuate myocardial and systemic activation of MMPs if administered prior to CPB.

Change History

Complete list of historical versions of study NCT00246740 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

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 ]

Original Secondary Outcome Measures ^ICMJE

Descriptive Information

Brief Title ^ICMJE

Protection of the Heart With Doxycycline During Coronary Artery Bypass Grafting

Official Title ^ICMJE

Protection of the Heart With Doxycycline During Coronary Artery Bypass Grafting: A Pilot Study

Brief Summary

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).

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.

Study Phase

Study Type ^ICMJE

Interventional

Study Design ^ICMJE

Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment

Condition ^ICMJE

Coronary Artery Bypass Grafting
Cardiopulmonary Bypass
Reperfusion Injury

Intervention ^ICMJE

Drug: Periostat

Study Arms / Comparison Groups

Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Active, not recruiting

Estimated Enrollment ^ICMJE

Estimated Completion Date

May 2009

Primary Completion Date

May 2008 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Gender

Both

Ages

18 Years to 80 Years

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Location Countries ^ICMJE

Canada

Administrative Information

NCT ID ^ICMJE

NCT00246740

Responsible Party

Dr. Barry Finegan, University of Alberta

Study ID Numbers ^ICMJE

Protect Study Protocol

Study Sponsor ^ICMJE

University of Alberta

Collaborators ^ICMJE

Investigators ^ICMJE

Principal Investigator:

Barry A Finegan, MB, FFARS(I), FRCPC

Department of Anesthesiology and Pain Medicine, University of Alberta Hospital

Information Provided By

University of Alberta

Verification Date

November 2008

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP