Coronary Artery Disease
Conditions
Keywords
Atrial Fibrillation, Cardiac surgery, Coronary Artery Bypass Graft, CorMatrix extra cellular matrix, Heart surgery, Inflammatory Biomarkers, Myocardial Infarction, identify proteomic inflammatory biomarkers
Brief summary
The objective of this study is to identify proteomic inflammatory biomarkers to determine if there are differences in the biomarkers in patients who are treated using the CorMatrix ECM implant to close the pericardium and the patients whose pericardium is left open (the current standard of care).
Detailed description
The pericardium's main function is to secrete proteins that ensure proper functioning within the pericardial space and to maintain pericardial pressure. Once dissected the pericardium is usually left open at the end of surgery due to the difficulty in realigning the edges and to avoid adverse effects cause by an inflammatory response. The body's inflammatory response is one of protection and healing of an injury. However many of the inflammatory biomarkers released can cause adverse outcomes after cardiac surgery, including: renal failure, myocardial infarction, atrial fibrillation, stroke and death. CorMatrix extra cellular matrix (ECM) Technology is a Food and Drug Administration (FDA) approved unique extra cellular implant material used for pericardial closure and reconstruction. Pericardial reconstruction using porcine intestinal ECM is a novel application. ECM combines the innate attributes of nature with the precision of science to help the heart heal itself. It is an acellular biomaterial that does not encapsulate when surgically implanted, but is gradually remodeled, leaving behind organized and healthy tissue. The body's tissue begins remodeling at the surgical site while the ECM maintains the needed tissue support. When implanted, the ECM acts as a scaffold into which the patient's cells migrate and integrate, stimulating the patient's natural wound-healing mechanisms. As the patient's cells become active, they lay down their own collagen, which matures over time to form strong and permanent tissue repair without leaving behind permanent foreign material. Because the ECM contains primarily collagen, the device is gradually replaced as the patient's tissue gradually turns over in a natural state of self-renewal. A retrospective study compared the incidence of post operative atrial fibrillation (POAF) in patients treated with the CorMatrix ECM for pericardial closure following isolated coronary artery bypass graft (CABG) versus patients not treated with the patch. The retrospective study comprised of 222 patients. 111 were treated with the CorMatrix ECM and the other 111 were not. Results showed POAF in 34 of 111 control patients but only 20 in 111 CorMatrix ECM treated patients, indicating a 54% decrease in the risk of POAF in the CorMatrix ECM treated patients. This study shows a statistically significant reduction in the risk of POAF in patients undergoing an isolated CABG with pericardial closure using the CorMatrix ECM. This is an unblinded, randomized study to identify proteomic inflammatory biomarkers to determine if there are differences in the biomarkers in patients who are treated using the CorMatrix ECM implant to close the pericardium and the patients whose pericardium is left open (the current standard of care). The study will be located at the Inova Heart and Vascular Institute (IHVI). The CorMatrix ECM will be implanted during the CABG surgical procedure in the IHVI cardiovascular operating rooms (CVOR). Sixty (60) patients who are routinely scheduled for a CABG will be recruited and randomly assigned to one of the two groups. There will be thirty (30) patients in each group. The control No Intervention group will not receive the CorMatrix ECM during surgery, leaving the pericardium open according to current standard of care. The treatment Cormatrix group will receive the CorMatrix ECM during surgery for the closure of the pericardium according to the specific recommended surgical technique. Pericardial fluid and blood samples will be collected from all patients. Pericardial fluid and blood samples will undergo novel nanoparticle based biomarker discovery technology to harvest proteomic biomarkers at the George mason University. In addition, patients will have their cardiac rhythm continually assessed during their hospital stay and then at their follow up appointments with their surgeon and cardiologist to determine whether they developed POAF post discharge. Both genders, greater than eighteen (18) years of age, will be included in the research. There are no enrollment restrictions based upon race or ethnic origin and it is expected their inclusion will be representative of the population undergoing CABG at IHVI. Pregnant women are excluded from the study.
Interventions
DEVICECorMatrix extra cellular matrix (ECM)
* Cormatrix ECM group will receive the CorMatrix ECM during surgery for the closure of the pericardium according to the specific recommended surgical technique. * No Intervention group will not receive the CorMatrix ECM during surgery, leaving the pericardium open according to current standard of care.
Sponsors
Corvivo Cardiovascular, Inc.
Inova Health Care Services
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is ≥18 years of age * Subject must be selected as a candidate for isolated Coronary Artery Bypass Graft (CABG) procedure * Subject has a Left Ventricular Ejection Fraction (LVEF) of ≥30% * Subject is able and willing to provide written informed consent and HIPAA authorization * Subject has a life expectancy of at least one year
Exclusion criteria
* Subject is scheduled for other concomitant surgical procedures (carotid surgery included) * Subject has a known hypersensitivity to porcine material * Subject has a religious or cultural objection to the use of blood or porcine products * Subject is scheduled for Off Pump Coronary Artery Bypass procedures (OPCAB) * Subject has a history of diagnosed treated or un-treated pre-operative atrial fibrillation or any other type of cardiac arrhythmia * Subject has a history of anti-arrhythmic drug treatment in the past six (6) months * Subject has an implantable cardiac device (e.g., pacemakers, implantable cardioverter defibrillators) * Subject has a history of an accessory pathway disorder (e.g., Wolff-Parkinson-White syndrome) * Subject has a documented myocardial infarction (MI) within six (6) weeks prior to study enrollment * Subject needs emergent cardiac surgery (i.e., cardiogenic shock) * Subject requires intra-aortic balloon pump or intravenous inotropes * Subject has had an infection within six (6) weeks preceding surgery requiring antibiotic therapy * Subject is on pre-surgical immunosuppressive therapy (corticosteroids included) * Subject has chronic inflammatory disease (leukemia, lymphoma, arthritis, rheumatoid, lupus, Crohn's disease, ulcerative colitis, hepatitis C, HIV) * Subject has had therapeutic radiation to the pericardium, either prior to surgery or expected during the three (3) week period following surgery * There is an inability to approximate the graft and pericardium edge along the entire extent of the defect * Subject is incarcerated * Subject is participating in concomitant research studies of investigational products (e.g., Appendage closure devices, septal defect patches) * Subject is unable to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Inflammatory Cytokine Levels in Participant Sera From Pre-surgery Baseline to Day 3 Post-surgery. | Baseline and and Post-Op day 3 | Percentage change in Inflammatory Cytokine Levels in serum derived from participant blood sample that underwent novel nanoparticle-based biomarker harvesting technology to capture and isolate global low molecular weight (LMW) proteome. Peptides from captured proteomes are detected with reversed-phase liquid chromatography/electrospray tandem mass spectrometry (LC-MS/MS). Inflammatory cytokines include Interleukin 6 (IL6), Interleukin 8 (IL8), Interleukin 2 Receptor (IL2R), Tumor Necrosis Factor (TNF), and Lipopolysaccharide Binding Protein (LBP). The measure of their respective levels is defined here as the Spectral Count from LC-MS/MS analysis. Percentage change of Spectral Counts is the difference of Day 3 post-surgery and pre-surgical baseline relative to the pre-surgical baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrences of Post Operative Atrial Fibrillation (POAF) | Up to 30 days post surgery | Number of patients that were determined to have Post Operative Atrial Fibrillation by electrocardiograph within 30 days of surgery |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CorMatrix Group The treatment Cormatrix group will receive the CorMatrix ECM during surgery for the closure of the pericardium according to the specific recommended surgical technique.
CorMatrix extra cellular matrix (ECM): - Cormatrix ECM group will receive the CorMatrix ECM during surgery for the closure of the pericardium according to the specific recommended surgical technique.
\- No Intervention group will not receive the CorMatrix ECM during surgery, leaving the pericardium open according to current standard of care. | 20 |
| Control The control No Intervention group will not receive the CorMatrix ECM during surgery, leaving the pericardium open according to current standard of care. | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Data collection error | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | CorMatrix Group | Control | Total |
|---|---|---|---|
| Age, Continuous | 61.18 years STANDARD_DEVIATION 9.88 | 60.17 years STANDARD_DEVIATION 9.84 | 60.30 years STANDARD_DEVIATION 9.93 |
| Region of Enrollment United States | 20 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 17 Participants | 18 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Change in Inflammatory Cytokine Levels in Participant Sera From Pre-surgery Baseline to Day 3 Post-surgery.
Percentage change in Inflammatory Cytokine Levels in serum derived from participant blood sample that underwent novel nanoparticle-based biomarker harvesting technology to capture and isolate global low molecular weight (LMW) proteome. Peptides from captured proteomes are detected with reversed-phase liquid chromatography/electrospray tandem mass spectrometry (LC-MS/MS). Inflammatory cytokines include Interleukin 6 (IL6), Interleukin 8 (IL8), Interleukin 2 Receptor (IL2R), Tumor Necrosis Factor (TNF), and Lipopolysaccharide Binding Protein (LBP). The measure of their respective levels is defined here as the Spectral Count from LC-MS/MS analysis. Percentage change of Spectral Counts is the difference of Day 3 post-surgery and pre-surgical baseline relative to the pre-surgical baseline.
Time frame: Baseline and and Post-Op day 3
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CorMatrix Group | Change in Inflammatory Cytokine Levels in Participant Sera From Pre-surgery Baseline to Day 3 Post-surgery. | LBP (Lipopolysaccharide Binding Protein) | 190 Percent Change | Standard Error 45 |
| CorMatrix Group | Change in Inflammatory Cytokine Levels in Participant Sera From Pre-surgery Baseline to Day 3 Post-surgery. | IL8 (Interleukin 8) | 44 Percent Change | Standard Error 2 |
| CorMatrix Group | Change in Inflammatory Cytokine Levels in Participant Sera From Pre-surgery Baseline to Day 3 Post-surgery. | IL2R (Interleukin 2 Receptor) | 35 Percent Change | Standard Error 29 |
| CorMatrix Group | Change in Inflammatory Cytokine Levels in Participant Sera From Pre-surgery Baseline to Day 3 Post-surgery. | TNF (Tumor Necrosis Factor) | 5 Percent Change | Standard Error 3 |
| CorMatrix Group | Change in Inflammatory Cytokine Levels in Participant Sera From Pre-surgery Baseline to Day 3 Post-surgery. | IL6 (Interleukin 6) | 645 Percent Change | Standard Error 400 |
| Control | Change in Inflammatory Cytokine Levels in Participant Sera From Pre-surgery Baseline to Day 3 Post-surgery. | TNF (Tumor Necrosis Factor) | 7 Percent Change | Standard Error 5 |
| Control | Change in Inflammatory Cytokine Levels in Participant Sera From Pre-surgery Baseline to Day 3 Post-surgery. | LBP (Lipopolysaccharide Binding Protein) | 197 Percent Change | Standard Error 57 |
| Control | Change in Inflammatory Cytokine Levels in Participant Sera From Pre-surgery Baseline to Day 3 Post-surgery. | IL6 (Interleukin 6) | 767 Percent Change | Standard Error 380 |
| Control | Change in Inflammatory Cytokine Levels in Participant Sera From Pre-surgery Baseline to Day 3 Post-surgery. | IL2R (Interleukin 2 Receptor) | 31 Percent Change | Standard Error 25 |
| Control | Change in Inflammatory Cytokine Levels in Participant Sera From Pre-surgery Baseline to Day 3 Post-surgery. | IL8 (Interleukin 8) | 28 Percent Change | Standard Error 16 |
Secondary
Occurrences of Post Operative Atrial Fibrillation (POAF)
Number of patients that were determined to have Post Operative Atrial Fibrillation by electrocardiograph within 30 days of surgery
Time frame: Up to 30 days post surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CorMatrix Group | Occurrences of Post Operative Atrial Fibrillation (POAF) | 2 Participants |
| Control | Occurrences of Post Operative Atrial Fibrillation (POAF) | 0 Participants |