Protection of the Heart With Doxycycline During Coronary Artery Bypass Grafting
Information source: University of Alberta
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Coronary Artery Bypass Grafting; Cardiopulmonary Bypass; Reperfusion Injury
Intervention: Periostat (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: University of Alberta Official(s) and/or principal investigator(s):
Barry A Finegan, MB, FFARS(I), FRCPC, Principal Investigator, Affiliation: Department of Anesthesiology and Pain Medicine, University of Alberta Hospital
Overall contact:
Barry A Finegan, MB, FFARS(I), FRCPC, Phone: 780-407-8887, Email: bfinegan@ualberta.ca
Summary
The purpose of this study is to determine whether doxycycline at a sub-antimicrobial dose
(Periostat) will decrease reperfusion injury after coronary artery bypass grafting (CABG)
surgery with cardiopulmonary bypass (CPB).
Clinical Details
Official title: Protection of the Heart With Doxycycline During Coronary Artery Bypass Grafting: A Pilot Study
Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment
Primary outcome: 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.
Secondary outcome: 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.
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
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
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
Locations and Contacts
Barry A Finegan, MB, FFARS(I), FRCPC, Phone: 780-407-8887, Email: bfinegan@ualberta.ca
University of Alberta Hospital, Edmonton, Alberta T6G 2G3, Canada; Recruiting
Costas J Schulze, MD, Sub-Investigator
Richard Schulz, PhD, Sub-Investigator
Shao Hua Wang, MD, Sub-Investigator
Craig Guenther, MD, Sub-Investigator
Arvind Koshal, MD, Sub-Investigator
Additional Information
Starting date: October 2005
Ending date: May 2008
Last updated: May 22, 2008
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