Protection of the Heart With Doxycycline During Coronary Artery Bypass Grafting

NCT00246740 | Completed Phase 2 Results

• 1 other identifier: Protect Study Protocol
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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).

Conditions

Coronary Artery Bypass Grafting; Cardiopulmonary Bypass; Reperfusion Injury

Keywords

Doxycycline; coronary artery bypass grafting

Outcome Measures

Primary Outcomes (1)

• Left Ventricular Stroke Work Index (LVSWI)

  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 Outcomes (8)

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

  Before surgery and 10 minutes reperfusion after surgery

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

  Before surgery and 10 minutes reperfusion after surgery

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

  Before surgery and up to 72 h reperfusion after surgery

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

  Before surgery and up to 72 h reperfusion after surgery

• Venous Plasma Concentration of Troponin-I

  Before surgery and 10 minutes reperfusion after surgery

Study Arms (2)

Placebo oral tablet

PLACEBO COMPARATOR

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).

Drug: Placebo Oral Tablet

Periostat

EXPERIMENTAL

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).

Drug: Periostat

Interventions

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.

Also known as: Doxycycline

Periostat

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.

Also known as: Placebo

Placebo oral tablet

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Aged 18 through 80 years, inclusive
• Scheduled for primary CABG surgery with CPB

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (1)

University of Alberta Hospital

Edmonton, Alberta, T6G 2G3, Canada

Location

Related Publications (1)

• Schulze CJ, Castro MM, Kandasamy AD, Cena J, Bryden C, Wang SH, Koshal A, Tsuyuki RT, Finegan BA, Schulz R. Doxycycline reduces cardiac matrix metalloproteinase-2 activity but does not ameliorate myocardial dysfunction during reperfusion in coronary artery bypass patients undergoing cardiopulmonary bypass. Crit Care Med. 2013 Nov;41(11):2512-20. doi: 10.1097/CCM.0b013e318292373c.

  PMID: 23928836 RESULT

Related Links

• DOI of published results paper

MeSH Terms

Conditions

Reperfusion Injury

Interventions

Doxycycline

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Limitations and Caveats

Small sample size. LVSWI does not estimate diastolic dysfunction. Right atrial biopsies may not reflect changes in left ventricular MMP activity. Doxycycline dose- and time-response analyses is required to better assess the protective effects

Results Point of Contact

• Title: Dr Richard Schulz
• Organization: Departments of Pediatrics and Pharmacology, University of Alberta

richard.schulz@ualberta.ca

780-492-6581

Study Officials

• Barry A Finegan, FFARCS FRCPC

  Department of Anesthesiology and Pain Medicine, University of Alberta Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 28, 2005
• First Posted: October 31, 2005
• Study Start: October 1, 2005
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2009
• Last Updated: December 15, 2017
• Results First Posted: December 15, 2017

Record last verified: 2017-05

Locations

CA (1)