Coronary Artery Bypass GraftingPhase 2NCT00246740
Protection of the Heart With Doxycycline During Coronary Artery Bypass Grafting
A Phase 2 study testing Periostat in people with Coronary Artery Bypass Grafting and Cardiopulmonary Bypass, run by University of Alberta at 1 site in Canada.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Coronary Artery Bypass Grafting, Cardiopulmonary Bypass, Reperfusion Injury
- What is being tested?
- Periostat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 1 siteCanada
- Study dates
- Oct 2005to May 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent
- Aged 18 through 80 years, inclusive
- Scheduled for primary CABG surgery with CPB
Who cannot join
- 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
Show all 9Show fewer
- Pre-operative ventricular pacing or left bundle branch block (LBBB)
- Known hypersensitivity to tetracycline class antibiotics
- Renal failure requiring dialysis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Protection of the Heart With Doxycycline During Coronary Artery Bypass Grafting: A Pilot Study
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).
Read the 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.
- Being tested
- Periostat, Placebo Oral Tablet
- Keywords
- Doxycycline, coronary artery bypass grafting
- Medical subject headings
- Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PeriostatDrug
Also called Doxycycline
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.
Placebo Oral TabletDrug
Also called Placebo
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Drug: Periostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Before surgery up to 24h of reperfusion
Secondary outcomes (8)
Cardiac Matrix Metalloproteinase-9 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion
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
Measured: Before surgery and 10 minutes reperfusion after surgery
Cardiac Matrix Metalloproteinase-2 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion
Biochemical activity of MMP-2 activity in right atrial biopsies, measured at 10 minutes of reperfusion after surgery.
Measured: Before surgery and 10 minutes reperfusion after surgery
Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion
Biochemical activity of MMP-9 activity in venous plasma, measured before surgery and up to 72h of reperfusion after surgery.
Measured: Before surgery and up to 72 h reperfusion after surgery
Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion
Biochemical activity of MMP-2 activity in venous plasma, measured before surgery and up to 72h of reperfusion after surgery.
Measured: Before surgery and up to 72 h reperfusion after surgery
Venous Plasma Concentration of Troponin-I
Measurement of levels of TnI (troponin-I), a marker of cardiac cell damage
Measured: Before surgery and 10 minutes reperfusion after surgery
Cleaved TroponinI/GAPDH Ratios in Right Atrial Biopsy
Measurement of the ratios of cleaved TnI (troponin-I) versus GAPDH in biopsies collected from right atria. Measure is the ratio TnI/GAPDH
Measured: Before surgery and 10 minutes reperfusion after surgery
Venous Plasma Concentration of C-reactive Protein
Measurement of inflammation marker C-reactive protein in plasma
Measured: Before surgery and up to 72 h reperfusion after surgery
Venous Plasma Concentration of IL-6
Measurement of inflammation marker interleukin-6 in plasma
Measured: Before surgery and up to 72 h reperfusion after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2005 (estimated)
- Study startOct 2005
- Primary completionMay 2008
- Study completionMay 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery Bypass GraftingStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Barry Finegan, University of Alberta
- Investigators
- Barry A Finegan, FFARCS FRCPC, Principal investigator, Department of Anesthesiology and Pain Medicine, University of Alberta Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00246740
- Sponsor's protocol ID
- Protect Study Protocol
- Status last verified
- May 2017
- First submitted
- 28 Oct 2005
- Last updated
- 15 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 23928836
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protection of the Heart With Doxycycline During Coronary Artery Bypass Grafting: A Pilot Study
- ClinicalTrials.gov ID
- NCT00246740
- Acronym / sponsor ID
- Protect Study Protocol
- Keywords
- Doxycycline, coronary artery bypass grafting
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Study start
- Oct 2005
- Primary completion
- May 2008 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 31 Oct 2005 (estimated)
- Results
- Posted 15 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo oral tablet | Placebo comparator | Drug: Placebo Oral TabletPatients 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). |
| Periostat | Experimental | Drug: PeriostatPatients 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). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Written informed consent
- Aged 18 through 80 years, inclusive
- Scheduled for primary CABG surgery with CPB
Key exclusion criteria (9 listed)
- Females of childbearing potential
- Emergency CABG
- Previous sternotomy
- Planned simultaneous surgery (i.e. valve repair or carotid endarterectomy)
- Myocardial infarction within 48 hours
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PeriostatAlso: DoxycyclineIn 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. | Drug | Periostat |
| Placebo Oral TabletAlso: PlaceboIn 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. | Drug | Placebo oral tablet |
Primary outcome
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.
8 secondary outcomes
Cardiac Matrix Metalloproteinase-9 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion
Time frame: 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
Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion
Time frame: 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
Venous Plasma Concentration of Troponin-I
Time frame: 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
Venous Plasma Concentration of C-reactive Protein
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23928836Schulze 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.
- DOI of published results paperLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Coronary Artery Bypass Graft (CABG)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Barry A Finegan, FFARCS FRCPC principal investigator
Department of Anesthesiology and Pain Medicine, University of Alberta Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Periostat in people with Coronary Artery Bypass Grafting and Cardiopulmonary Bypass, run by University of Alberta at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Left Ventricular Stroke Work Index (LVSWI) (time frame: Before surgery up to 24h of reperfusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00246740, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2017.