Phase III Study of Metabolic Intervention With Glutamate in Coronary Surgery II
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 321
- 试验地点
- 4
- 主要终点
- Postoperative Increase of Plasma NT-proBNP
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •LVEF ≤ 0.50
- •CCS class IV
- •Recent Myocardial Infarct (≤ 90 days)
- •Emergency / Urgent procedure (as defined in EuroSCORE II)
- •CABG with aortic or mitral valve procedure
- •LVEF ≤ 0.30 regardless of EuroSCORE II
排除标准
- •age > 85 years
- •ambiguous food allergies that trigger shortness of breath, headache or flushing
- •previous cardiac surgery
- •patients who are in such bad condition that they cannot be asked to participate
- •patients who because of linguistic or other reasons are unable to provide informed consent
- •severe renal failure with preoperative dialysis or calculated GFR <30 mL / min
- •patients requiring mechanical circulatory support (intra-aortic balloon pump) due to circulatory failure before they are enrolled in the study
- •surgery without heart-lung machine (off-pump)
- •concomitant Maze-procedure
- •surgery of ascending aorta
- •surgery of both aortic and mitral valve
研究组 & 干预措施
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.
干预措施: saline infusion (Drug)
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.
干预措施: glutamate infusion (Drug)
结局指标
主要结局
Postoperative Increase of Plasma NT-proBNP
时间窗: from the day before surgery to the third postoperative day
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.
次要结局
- Number of Participants With Incidence of Stroke(within 24 hours from surgery)
- Postoperative Plasma Level of NT-proBNP(third postoperative day)
- Incidence of Mortality(up to 30 days)
- Incidence of Unexpected Adverse Events(within 24 hours from infusion)
研究者
Rolf Svedjeholm
Professor, MD
University Hospital, Linkoeping