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| ID | Type | Description | Link |
|---|---|---|---|
| Dnr 5.1-2015-77379 | Other Identifier | Swedish Medical Product Agency |
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| Name | Class |
|---|---|
| Region Örebro County | OTHER |
| University Hospital, Umeå | OTHER |
| Sahlgrenska University Hospital | OTHER |
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The aim of GLUTAMICS II is to evaluate whether intravenous glutamate infusion surgery reduces the risk of postoperative heart failure as measured by plasma NT-proBNP in patients undergoing moderate to high-risk coronary artery bypass graft surgery. Patients accepted for coronary artery bypass surgery of at least two vessel disease or left main stenosis with or without concomitant procedure and considered to be at moderate to high surgical risk preoperatively with regard to postoperative heart failure will be studied. The primary endpoint is postoperative increase of NT-proBNP from the day before surgery to the third postoperative day.
In spite of the progress in cardiac surgery and perioperative management postoperative heart failure remains the leading cause of death and organ failure. Although acknowledged as a major problem in cardiac surgery there are no generally accepted criteria for the diagnosis of postoperative heart failure. This in turn could explain why treatment for postoperative heart failure is poorly documented with regard to clinical outcome.
Ischemia prior to cardiopulmonary bypass is the main cause of myocardial infarction after CABG. Available data demonstrate that ischemia and evolving myocardial infarction account for a large proportion of patients with postoperative heart failure after CABG.
Conventional treatment of postoperative heart failure presents a therapeutic dilemma as inotropic drugs not only aggravate ischemia and increase the size of evolving myocardial infarction, but also stimulate apoptotic processes that may have adverse long-term consequences.
The role of inotropes in cardiac surgery is therefore controversial. Some authors claim that liberal use of inotropes and goal-directed haemodynamic therapy can improve outcome whereas other report that liberal use of inotropes is associated with increased morbidity and mortality.
Alternative measures that can enhance myocardial recovery and function without putting further strain on the heart are therefore desirable.
Glutamate could influence outcome after myocardial ischemia by two different biochemical mechanisms. First, glutamate improves myocardial tolerance to ischemia by facilitated anaerobic metabolism and substrate level phosphorylation during ischemia. The second mechanism is related to the anaplerotic role of glutamate. Glutamate plays a key role for replenishment of Krebs cycle intermediates lost during ischemia, which enhances post-ischemic recovery of myocardial oxidative metabolism and function.
Promoting metabolic and functional recovery with metabolic support represents a novel concept in the treatment of heart failure after acute ischemia. Animal experiments suggest that glutamate increases myocardial tolerance to ischemia and that glutamate promotes post-ischemic recovery. Intravenous glutamate improved metabolic and hemodynamic recovery in humans early after CABG. Early clinical experience with intravenous metabolic support showed that the need for inotropes could be substantially reduced while clinical outcomes with regard to postoperative mortality, postoperative renal dysfunction and long-term survival compared favourably with the literature. This encouraging experience contributed to the initiation of the first GLUTAMICS-trial.
The first GLUTAMICS-trial investigated if intravenous glutamate infusion given in association with surgery for acute coronary syndrome could prevent myocardial injury, postoperative heart failure and reduce mortality. The study was negative with regard to the primary endpoint, which was a composite of postoperative mortality, perioperative myocardial infarction and left ventricular failure at weaning from cardiopulmonary bypass.
However, the study included a high proportion of low risk patients. Furthermore, the design of the primary endpoint suffered from liberal preemptive use of inotropes in patients anticipated to have weaning problems. It became evident at clinical endpoint committee meetings that preemptive use of inotropes prevented detection of weaning problems in patients who later developed severe heart failure. The secondary endpoint severe circulatory failure discriminated mild short-lasting heart failure at weaning from cardiopulmonary bypass from clinically significant heart failure requiring substantial circulatory support and leading to prolonged ICU stay or death. In the glutamate treated patients the relative risk of developing severe circulatory failure was reduced by more than 50% in most risk groups undergoing isolated CABG.
The first GLUTAMICS trial also included a substudy consisting of a blinded evaluation of NT-proBNP as a marker for postoperative heart failure.
Due to the lack of generally accepted criteria for postoperative heart failure, the evaluation of treatment is difficult. Consequently, comparative studies on different treatment strategies of heart failure after cardiac surgery are sparse given the magnitude of the problem.
Natriuretic peptides have been extensively studied in cardiology. In patients with chronic heart failure markedly increased BNP and NT-pro BNP levels are associated with poor prognosis. The response of natriuretic peptides to heart failure treatment has significant prognostic implications, and non-responders have a poor prognosis.
In cardiac surgery NT-proBNP increase was more pronounced in patients requiring inotropes. High postoperative levels of BNP and NT-proBNP were associated with worse outcome, both in the short- and long-term.
The first GLUTAMICS-trial permitted a blinded prospective evaluation of NT-proBNP by a clinical end-points committee relying on strict prespecified criteria with regard to postoperative heart failure. Data to be published demonstrate that postoperative NT-proBNP (day 1 and day 3) levels were strong predictors for severe heart failure associated with extended ICU stay or death. This implies that postoperative NT-proBNP could serve as a measure to assess efficacy of treatment and preventive strategies for postoperative heart failure. Albeit, a surrogate marker for postoperative heart failure it provides the advantage of a standardized and objective analysis, which makes the study reproducible.
AIM
The aim is to confirm findings in subgroups from the first GLUTAMICS-trial that intravenous glutamate infusion reduces the risk of postoperative heart failure in moderate to high risk patients undergoing coronary artery surgery by showing a reduced increase of NT-proBNP postoperatively.
PATIENTS
Patients accepted for coronary artery bypass surgery of at least two vessel disease or left main stenosis with or without concomitant procedure considered to be at moderate to high surgical risk preoperatively with regard to postoperative heart failure.
310 patients are planned to be included after informed written consent.
Exclusion criteria: patients with ambiguous food allergies that trigger shortness of breath, headache or flushing; patients> 85 years, previous cardiac surgery, patients who are in such bad condition that they cannot be asked to participate, patients who for linguistic or other reasons are unable to provide informed consent, severe renal failure with preoperative dialysis or calculated GFR <30 mL / min, patients requiring inotropic drugs or mechanical circulatory support (intra-aortic balloon pump) due to circulatory failure even before they enrolled in the study, patients who undergo surgery without the heart-lung machine (off-pump), patients who undergo concomitant Maze-procedure or surgery of ascending aorta.
STUDY DESIGN
The GLUTAMICS II is an investigator initiated prospective, randomized, placebo controlled, double-blind trial with parallel assignment to glutamate or placebo (saline). The trial is externally randomized and randomization is stratified for patients undergoing isolated CABG and for those having CABG with concomitant procedure.
INTERVENTION
Patients are randomly allocated to blinded intravenous infusion of 0.125M L-glutamic acid solution or saline at a rate of 1.65 ml/kg and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.
PRIMARY ENDPOINT
The primary endpoint is a postoperative increase of NT-proBNP from the day before surgery to the third postoperative day.
SECONDARY ENDPOINTS
Secondary endpoints are the absolute postoperative plasma levels of NT-proBNP day 1 and day 3.
SAFETY VARIABLES
Postoperative mortality (30 days + hospitals), stroke within 24 hours and SUSARs
SAMPLE SIZE
Sample size is based on available results from the first GLUTAMICS study. In that study, the following increase of NT-proBNP from the preoperative value to third postoperative day (mean ± SD) were observed in patients with LVEF ≤ 0.30 or EuroSCORE II ≥ 3.0 undergoing coronary artery surgery for with or without concomitant procedure.
Glutamate (n=71): 5261 ± 4409
Placebo (n=62): 7112 ± 6454
Sample size assessment by external statistical expertise (80% power, 5% risk level; two-sided test) suggests 141 patients in each group. To account for failed sampling and other loss we plan a total of 310 patients.
INTERIM ANALYSIS
Interim analysis will be performed by an external independent statistician after 160 patients by an adaptive design as reported in detail to the Swedish Medical Product Agency.
Update August 30, 2020: Interim analysis in December 2017 supported the original sample size assessment and the aim was set to reach 300 patients with complete data for the primary endpoint. The original goal of 280 patients with complete data has been reached and the study is approaching 300 but as study solutions will expire September 30, 2020 this will be the last date for inclusion of patients into the trial.
ETHICAL CONSIDERATIONS
A concern with the use of glutamate is that it may act as an excitotoxin under certain conditions and participate in events leading to neurological damage. However, brain tissue concentrations of glutamate are more than fifty-fold higher than in blood whereas the dosage used only elevates blood levels three-fold. Neurological outcome has been carefully monitored when intravenous infusions have been used in clinical practice without evidence of adverse effects. No evidence of subclinical neurological injury associated with intravenous glutamate infusion could be detected by the S-100B measurements and no differences in neurological outcome or other adverse events were found in the GLUTAMICS trial.
After written informed consent eligible patients will be enrolled in the study. The study will be performed according to the Helsinki Declaration of Human Rights and is approved by the Regional Ethical Review Board in Linköping (Dnr 2011/498-31; Dnr 2015/333-32).
The Swedish Medical Products Agency requests surveillance and unblinding in cases of CT-verified stroke within 24 hours of surgery, mortality and suspected unexpected serious adverse reactions (SUSAR). External monitoring of all key data, written informed consent and unblinding procedures will be done.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intravenous glutamate infusion | Active Comparator | Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. |
|
| Intravenous saline infusion | Placebo Comparator | Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| glutamate infusion | Drug | Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. |
| Measure | Description | Time Frame |
|---|---|---|
| Postoperative Increase of Plasma NT-proBNP | Postoperative increase of NT-proBNP reflects postoperative myocardial dysfunction sustained in association with surgery. NT-proBNP usually peaks on the third to fourth postoperative day after coronary artery bypass surgery. In the first GLUTAMICS trial a good agreement between hemodynamic criteria for postoperative heart failure and postoperative NT-proBNP was found. | from the day before surgery to the third postoperative day |
| Measure | Description | Time Frame |
|---|---|---|
| Postoperative Plasma Level of NT-proBNP | Postoperative NT-proBNP reflects postoperative myocardial dysfunction. | first postoperative day |
| Postoperative Plasma Level of NT-proBNP | Postoperative NT-proBNP reflects postoperative myocardial dysfunction. |
| Measure | Description | Time Frame |
|---|---|---|
| Copeptin Substudy | Exploratory assessment of plasma-Copeptin related to NT-proBNP | preoperative, first and third postoperative day |
Inclusion Criteria:
Patients accepted for coronary artery bypass surgery of at least two vessel disease or left main stenosis with or without concomitant procedure considered to be at moderate to high surgical risk preoperatively with regard to postoperative heart failure due to:
• EuroSCORE II ≥ 3.0 with at least one of the following cardiac or procedure related risk factors:
OR
• LVEF ≤ 0.30 regardless of EuroSCORE II
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rolf Svedjeholm, Professor | University Hospital, Linkoeping | Study Chair |
| Farkas Vanky, MD, PhD | University Hospital, Linkoeping | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sahlgrenska University Hospital | Gothenburg | SE41345 | Sweden | |||
| University Hospital Linköping |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9800828 | Background | O'Connor GT, Birkmeyer JD, Dacey LJ, Quinton HB, Marrin CA, Birkmeyer NJ, Morton JR, Leavitt BJ, Maloney CT, Hernandez F, Clough RA, Nugent WC, Olmstead EM, Charlesworth DC, Plume SK. Results of a regional study of modes of death associated with coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group. Ann Thorac Surg. 1998 Oct;66(4):1323-8. doi: 10.1016/s0003-4975(98)00762-0. | |
| 18497597 |
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321 patients gave written informed consent.
7 patients were not randomized ( change of procedure n=2; forgetfulness n=5)
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| ID | Title | Description |
|---|---|---|
| FG000 | Intravenous Glutamate Infusion | Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. glutamate infusion: Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. |
| FG001 | Intravenous Saline Infusion | Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. saline infusion: Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Intravenous Glutamate Infusion | Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. glutamate infusion: Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Postoperative Increase of Plasma NT-proBNP | Postoperative increase of NT-proBNP reflects postoperative myocardial dysfunction sustained in association with surgery. NT-proBNP usually peaks on the third to fourth postoperative day after coronary artery bypass surgery. In the first GLUTAMICS trial a good agreement between hemodynamic criteria for postoperative heart failure and postoperative NT-proBNP was found. | Incomlete sampling of NT-proBNP in the Glutamate infusion group (n=3) and Saline infusion group (n=5). | Posted | Mean | Standard Deviation | ng/L | from the day before surgery to the third postoperative day |
|
30 days
Adverse events agree with clinicaltrials.gov definitions but are mainly related to the surgical procedure
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Intravenous Glutamate Infusion | Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. glutamate infusion: Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Postoperative Atrial Fibrillation | Surgical and medical procedures | Systematic Assessment | Postoperative atrial fibrillation associated with more than one weeks hospital stay at the cardiac surgical unit |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Postoperative Atrial fibrillation | Surgical and medical procedures | Systematic Assessment | Postoperative atrial fibrillation not associated with hospital stay at the cardiac surgical unit exceeding one week |
The main limitations of the study are: (i) it relies on a surrogate marker for heart failure (ii) the proportion of patients with diabetes had almost doubled compared to the cohort used for the sample size estimation
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Jonas Holm | Linköping University Hospital | +46101034498 | jonas.holm@regionostergotland.se |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 1, 2016 | May 21, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D018698 | Glutamic Acid |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D005971 | Glutamates |
| D024342 | Amino Acids, Acidic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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|
|
| saline infusion | Drug | Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. |
|
|
| third postoperative day |
| Number of Participants With Incidence of Stroke | Postoperative stroke was defined as neurological or cognitive deficit with a cerebral injury verified on (Computed Tomography) CT-scan. All suspected cases of stroke underwent CT-scan. Stroke within 24 h of surgery was defined as a stroke that occurred within 24 h of surgery or signs of a stroke, when first assessable in deeply sedated patients on a ventilator. | within 24 hours from surgery |
| Incidence of Mortality | Postoperative mortality was defined as mortality within 30 days of surgery. | up to 30 days |
| Incidence of Unexpected Adverse Events | suspected unexpected serious adverse reaction | within 24 hours from infusion |
| Linköping |
| SE58185 |
| Sweden |
| University Hospital Örebro | Örebro | SE 70185 | Sweden |
| University Hospital Umeå | Umeå | SE90185 | Sweden |
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| 20829070 | Background | Nozohoor S, Nilsson J, Algotsson L, Sjogren J. Postoperative increase in B-type natriuretic peptide levels predicts adverse outcome after cardiac surgery. J Cardiothorac Vasc Anesth. 2011 Jun;25(3):469-75. doi: 10.1053/j.jvca.2010.07.002. Epub 2010 Sep 9. |
| 23695172 | Background | Fox AA, Nascimben L, Body SC, Collard CD, Mitani AA, Liu KY, Muehlschlegel JD, Shernan SK, Marcantonio ER. Increased perioperative b-type natriuretic peptide associates with heart failure hospitalization or heart failure death after coronary artery bypass graft surgery. Anesthesiology. 2013 Aug;119(2):284-94. doi: 10.1097/ALN.0b013e318299969c. |
| 38252440 | Derived | Holm J, Vanky F, Svedjeholm R. Association of Glutamate Infusion With Risk of Acute Kidney Injury After Coronary Artery Bypass Surgery: A Pooled Analysis of 2 Randomized Clinical Trials. JAMA Netw Open. 2024 Jan 2;7(1):e2351743. doi: 10.1001/jamanetworkopen.2023.51743. |
| 37657522 | Derived | Holm J, Vanky F, Svedjeholm R. Glutamate Infusion Reduces Myocardial Dysfunction after Coronary Artery Bypass Grafting According to NT-proBNP: Summary of 2 Randomized Controlled Trials (GLUTAmate for Metabolic Intervention in Coronary Surgery [GLUTAMICS I-II]). Am J Clin Nutr. 2023 Nov;118(5):930-937. doi: 10.1016/j.ajcnut.2023.08.012. Epub 2023 Aug 30. |
| 35533197 | Derived | Holm J, Ferrari G, Holmgren A, Vanky F, Friberg O, Vidlund M, Svedjeholm R. Effect of glutamate infusion on NT-proBNP after coronary artery bypass grafting in high-risk patients (GLUTAMICS II): A randomized controlled trial. PLoS Med. 2022 May 9;19(5):e1003997. doi: 10.1371/journal.pmed.1003997. eCollection 2022 May. |
| BG001 | Intravenous Saline Infusion | Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. saline infusion: Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| NTproBNP ng/L | Mean | Standard Deviation | ng/L |
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| OG001 | Intravenous Saline Infusion | Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. saline infusion: Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. |
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| Secondary | Postoperative Plasma Level of NT-proBNP | Postoperative NT-proBNP reflects postoperative myocardial dysfunction. | Posted | Mean | Standard Deviation | ng/L | first postoperative day |
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| Secondary | Postoperative Plasma Level of NT-proBNP | Postoperative NT-proBNP reflects postoperative myocardial dysfunction. | Posted | Mean | Standard Deviation | ng/L | third postoperative day |
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| Secondary | Number of Participants With Incidence of Stroke | Postoperative stroke was defined as neurological or cognitive deficit with a cerebral injury verified on (Computed Tomography) CT-scan. All suspected cases of stroke underwent CT-scan. Stroke within 24 h of surgery was defined as a stroke that occurred within 24 h of surgery or signs of a stroke, when first assessable in deeply sedated patients on a ventilator. | Posted | Count of Participants | Participants | within 24 hours from surgery |
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| Secondary | Incidence of Mortality | Postoperative mortality was defined as mortality within 30 days of surgery. | Posted | Count of Participants | Participants | up to 30 days |
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| Secondary | Incidence of Unexpected Adverse Events | suspected unexpected serious adverse reaction | Posted | Count of Participants | Participants | within 24 hours from infusion |
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| Other Pre-specified | Copeptin Substudy | Exploratory assessment of plasma-Copeptin related to NT-proBNP | Not Posted | preoperative, first and third postoperative day | Participants |
| Post-Hoc | Postoperative Increase of Plasma NT-proBNP in Patients Without Diabetes | Postoperative increase of NT-proBNP reflects postoperative myocardial dysfunction sustained in association with surgery. NT-proBNP usually peaks on the third to fourth postoperative day after coronary artery bypass surgery. Previous observations suggest a blunted effect of glutamate in diabetic hearts. | Posted | Mean | Standard Deviation | ng/L | from preoperative level to the third postoperative day |
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| 1 |
| 148 |
| 65 |
| 148 |
| 31 |
| 148 |
| EG001 | Intravenous Saline Infusion | Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. saline infusion: Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. | 6 | 155 | 79 | 155 | 31 | 155 |
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| Acute Kidney Injury | Surgical and medical procedures | Systematic Assessment | AKI defined as a postoperative increase of p-creatinine by at least 50% from preoperative level |
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| Reoperation for bleeding | Surgical and medical procedures | Systematic Assessment |
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| Periperative myocardial injury | Surgical and medical procedures | Systematic Assessment | CK-MB on the first postoperative day > 70 ug/L or Troponin-T on postoperative day 3 > 2000 ng/L |
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| Postoperative Stroke | Nervous system disorders | Systematic Assessment | Stroke during hospital stay. Postoperative stroke was defined as neurological or cognitive deficit with a cerebral injury verified on (Computed Tomography) CT-scan. All suspected cases of stroke underwent CT-scan. |
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Not provided
Not provided
| D000600 |
| Amino Acids, Dicarboxylic |
| D018846 | Excitatory Amino Acids |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |