- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00246740
Protection of the Heart With Doxycycline During Coronary Artery Bypass Grafting
Protection of the Heart With Doxycycline During Coronary Artery Bypass Grafting: A Pilot Study
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Alberta
-
Edmonton, Alberta, Canada, T6G 2G3
- University of Alberta Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo oral tablet
Patients received oral administration of matching placebo pills, twice a day at least 2 days prior to surgery, on the day of surgery, and for the first 3 postoperative days (via a nasogastric tube or orally when patients tolerated it).
|
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:
|
Experimental: Periostat
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 for the first 3 postoperative days (via a nasogastric tube or orally when patients tolerated it).
|
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:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Before surgery up to 24h of reperfusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Before surgery and 10 minutes reperfusion after surgery
|
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.
|
Before surgery and 10 minutes reperfusion after surgery
|
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.
|
Before surgery and up to 72 h reperfusion after surgery
|
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.
|
Before surgery and up to 72 h reperfusion after surgery
|
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
|
Before surgery and 10 minutes reperfusion after surgery
|
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
|
Before surgery and 10 minutes reperfusion after surgery
|
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
|
Before surgery and up to 72 h reperfusion after surgery
|
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
|
Before surgery and up to 72 h reperfusion after surgery
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Barry A Finegan, FFARCS FRCPC, Department of Anesthesiology and Pain Medicine, University of Alberta Hospital
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Protect Study Protocol
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Reperfusion Injury
-
University of ChileFondo Nacional de Desarrollo Científico y Tecnológico, ChileCompletedReperfusion Injury | Acute Myocardial Infarction | Ischemia-reperfusion Injury | Reperfusion Injury, Myocardial | Reperfusion ArrhythmiasChile
-
University of AarhusErasmus Medical Center; Fonden til Lægevidenskabens FremmeCompletedIschemia Reperfusion Injury | Ischaemia Reperfusion InjuryDenmark
-
University of AarhusCompletedReperfusion Injuries, Myocardial
-
Indonesia UniversityEnrolling by invitationReperfusion Injury, MyocardialIndonesia
-
Chinese PLA General HospitalUnknown
-
West Kazakhstan Medical UniversityRecruitingKidney Transplantation | Ischemic Reperfusion Injury | ReperfusionKazakhstan
-
Cukurova UniversityCompleted
-
Chinese PLA General HospitalUnknownReperfusion Injury, Myocardial
-
Shahid Beheshti University of Medical SciencesPooyesh DarouCompletedMyocardial Ischemic Reperfusion InjuryIran, Islamic Republic of
-
Samsung Medical CenterCompletedIschemia/Reperfusion Injury of Liver Graft | Ischemia/Reperfusion Injury of Kidney | Remote Ischemic PostconditioningKorea, Republic of
Clinical Trials on Placebo Oral Tablet
-
EstetraICON Clinical ResearchCompletedVasomotor Symptoms | Menopausal SymptomsUnited States, Canada
-
EicOsis Human Health Inc.RecruitingHealthy SubjectsNew Zealand
-
Harmony Biosciences, LLCActive, not recruitingMyotonic Dystrophy 1 | Excessive Daytime SleepinessUnited States, Canada
-
Syntrix Biosystems, Inc.National Institute on Drug Abuse (NIDA); DF/Net ResearchCompletedDiabetic Neuropathies | Neuropathic Pain | Pain, ChronicUnited States
-
University of OxfordNovo Nordisk A/SRecruitingDiabetes Mellitus, Type 2United Kingdom
-
Fulcrum TherapeuticsTerminated
-
EicOsis Human Health Inc.CompletedHealthy AdultsUnited States
-
The Mind Research NetworkTerminatedSmoking Cessation | Tobacco Use DisorderUnited States
-
Cara Therapeutics, Inc.CompletedChronic Kidney Diseases | PruritusUnited States
-
Sunshine Lake Pharma Co., Ltd.CompletedChronic Hepatitis CChina