Protection of the Heart With Doxycycline During Coronary Artery Bypass Grafting
Condition: Coronary Artery Bypass Grafting; Cardiopulmonary Bypass; Reperfusion Injury
MeSH terms: Reperfusion Injury
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Periostat; Placebo Oral Tablet
Intervention type(s): Drug; Drug
Intervention description(s): In addition to standard care, patients received oral administration of 20 mg of doxycycline twice a day at least 2 days prior to surgery, on the day of surgery, and on postoperative days 1, 2, and 3.; In addition to standard care, patients received oral administration of placebo twice a day at least 2 days prior to surgery, on the day of surgery, and on postoperative days 1, 2, and 3.
Other intervention name(s): Doxycycline; Placebo
Intervention MeSH terms: Doxycycline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Doxycycline; coronary artery bypass grafting