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Completed

NCT Number: NCT00246740

Protection of the Heart With Doxycycline During Coronary Artery Bypass Grafting

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).

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Key information

Conditions

Coronary Artery Bypass Grafting Cardiopulmonary Bypass Cardiovascular Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Postoperative Complications Reperfusion Injury Vascular Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Alberta Hospital

Edmonton, Alberta, T6G 2G3, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Periostat

Drug

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.

Other names: Doxycycline

Placebo oral tablet

Drug

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 names: Placebo

Primary outcomes

  1. Left Ventricular Stroke Work Index (LVSWI)

    Time frame: Before surgery up to 24h of reperfusion

    Measure of global left ventricular function. The formula used for calculation is: LVSWI= SI x MAP x 0.0144 LVSWI = Left Ventricular Stroke Work Index (g*m/m2) SI = Stroke Index (mL/beat/m2) MAP = Mean Arterial Pressure (mmHg) 0.0144 is a conversion term to equalize units.

Secondary outcomes

  1. Cardiac Matrix Metalloproteinase-9 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion

    Time frame: Before surgery and 10 minutes reperfusion after surgery

    Biochemical activity of MMP-9 activity in right atrial biopsies, measured at 10 minutes of reperfusion after surgery. To determine MMP-9 activity, 20 μg of total protein from both myocardial extracts and plasma were analyzed by gelatin zymography. For detailed methodology consult Cheung PY, Sawicki G, Wozniak M, et al: Matrix metalloproteinase-2 contributes to ischemia-reperfusion injury in the heart. Circulation 2000; 101:1833-1839

  2. Cardiac Matrix Metalloproteinase-2 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion

    Time frame: Before surgery and 10 minutes reperfusion after surgery

    Biochemical activity of MMP-2 activity in right atrial biopsies, measured at 10 minutes of reperfusion after surgery.

  3. Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion

    Time frame: Before surgery and up to 72 h reperfusion after surgery

    Biochemical activity of MMP-9 activity in venous plasma, measured before surgery and up to 72h of reperfusion after surgery.

  4. Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion

    Time frame: Before surgery and up to 72 h reperfusion after surgery

    Biochemical activity of MMP-2 activity in venous plasma, measured before surgery and up to 72h of reperfusion after surgery.

  5. Venous Plasma Concentration of Troponin-I

    Time frame: Before surgery and 10 minutes reperfusion after surgery

    Measurement of levels of TnI (troponin-I), a marker of cardiac cell damage

  6. Cleaved TroponinI/GAPDH Ratios in Right Atrial Biopsy

    Time frame: Before surgery and 10 minutes reperfusion after surgery

    Measurement of the ratios of cleaved TnI (troponin-I) versus GAPDH in biopsies collected from right atria. Measure is the ratio TnI/GAPDH

  7. Venous Plasma Concentration of C-reactive Protein

    Time frame: Before surgery and up to 72 h reperfusion after surgery

    Measurement of inflammation marker C-reactive protein in plasma

  8. Venous Plasma Concentration of IL-6

    Time frame: Before surgery and up to 72 h reperfusion after surgery

    Measurement of inflammation marker interleukin-6 in plasma

Sponsors and collaborators

Lead sponsor

University of Alberta

Other

Registry information

Official study title

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

Important dates

Study start
2005
Primary completion
2008
Study completion
2009
First posted
Oct 31, 2005
Registry last updated
Dec 15, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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