Protection of the Heart With Doxycycline During Coronary Artery Bypass Grafting

NCT ID: NCT00246740

Last Updated: 2017-12-15

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-10-31

Study Completion Date

2009-05-31

Brief Summary

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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

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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.

Conditions

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Coronary Artery Bypass Grafting Cardiopulmonary Bypass Reperfusion Injury

Keywords

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Doxycycline coronary artery bypass grafting

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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).

Group Type PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type 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.

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).

Group Type EXPERIMENTAL

Periostat

Intervention Type 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.

Interventions

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Periostat

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.

Intervention Type DRUG

Placebo Oral Tablet

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.

Intervention Type DRUG

Other Intervention Names

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Doxycycline Placebo

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Alberta

OTHER

Sponsor Role lead

Responsible Party

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Barry Finegan

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Barry A Finegan, FFARCS FRCPC

Role: PRINCIPAL_INVESTIGATOR

Department of Anesthesiology and Pain Medicine, University of Alberta Hospital

Locations

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University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

Countries

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Canada

References

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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.

Reference Type RESULT
PMID: 23928836 (View on PubMed)

Related Links

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Other Identifiers

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Protect Study Protocol

Identifier Type: -

Identifier Source: org_study_id