A Randomized Placebo Controlled Trial of Intravenous N-Acetylcysteine (NAC) As A Renal Protective Agent for Prevention of Renal Dysfunction Following Cardiopulmonary Bypass (CPB)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 104
- 主要终点
- The change in serum creatinine between NAC and placebo groups from preoperative baseline levels to peak postoperative levels after exposure to CPB.
研究概览
简要总结
N-acetylcysteine is a medication that has most commonly been used in the past to prevent liver damage after an acetaminophen overdose. N-acetylcysteine has also been used in patients with pre-existing kidney damage to prevent further kidney damage resulting from dye that is used in tests such as angiograms (dye studies). This study hopes to prove that this medication may also help to protect kidneys from the damage caused by the heart-lung machine during cardiac surgery. This damage to the kidneys happens to patients undergoing cardiac surgery requiring the use of the heart-lung machine. Kidney failure after surgery is a serious complication (2-30% of patients with kidney problems can develop it) and it can lead to short term and long-term dialysis as well as death (there is up to a 30% death rate once kidney failure develops). The study will test if intravenous N-acetylcysteine is safe and effective in preventing kidney problems after cardiac surgery using the heart-lung machine. Approximately 104 patients will be enrolled at Sunnybrook and Women's College Health Science Centre. The study has been reviewed and approved by the ethics committee at Sunnybrook and Women's College Health Science Centre. The study will compare the effects of N-acetylcysteine with those of placebo (salt solution). The study medication (either N-acetylcysteine or placebo) will be given in addition to your usual medication and surgical procedures.
详细描述
Background:
N-acetylcysteine (NAC) is an oral or intravenous agent that replenishes glutathione which in turn allows for the formation of glutathione peroxidase, an important enzyme in the degradation cascade of reactive free oxygen radicals. NAC has been shown to reduce recurrent cardiac events in the setting of ischemic injury, and help prevent progression of renal dysfunction in patients with chronic renal failure exposed to nephrotoxic dye for radiographic studies. Cardiopulmonary bypass (CPB) has been shown be nephrotoxic that may be through the production of oxygen free radicals produced as a consequence of: a systemic inflammatory response to the pump, renal hypoperfusion and loss of pulsatile flow to the kidney during CPB. Renal dysfunction post cardiac surgery can lead to short or long term dialysis, and an increase in mortality rate. NAC therefore may be an ideal agent to preserve renal function in those patients who require exposure to CPB and are at high risk of developing postoperative renal dysfunction. The hypothesis tested in this study is that IV NAC may minimize postoperative renal dysfunction sustained by exposure to the cardiopulmonary bypass circuit.
Objectives:
This study will answer the question of whether perioperative intravenous N-Acetylcysteine (NAC) will be effective in reducing postoperative renal dysfunction as measured by a change peak creatinine from baseline values greater than or equal to 50μmol/L between placebo and NAC groups in adult, elective patients at high risk of renal insufficiency following exposure to cardiopulmonary bypass (CPB). This study is a randomized, placebo controlled, double blind trial that addresses the following objective:
1.To determine if intravenous N-Acetylcysteine (NAC) is effective in reducing post cardiopulmonary bypass renal dysfunction.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- Double
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The study includes those patients with preoperative renal dysfunction (serum creatinine level 140 μmol/L or greater or a calculated glomerular filtration rate of 50 mL/min or less), or a risk factor score for postoperative renal dysfunction that adds up to 6 or more based on the following scale:
- •Score Risk Factor:
- •3 scheduled for redo cardiac surgery
- •3 scheduled for valve surgery
- •2 age greater than 69 at time of surgery
- •2 known diabetic (Type I or II)
- •2 congestive heart failure
- •2 treated hypertension
- •2 chronic obstructive pulmonary disease
- •2 preoperative stroke
- •1 left ventricular function -grade 3 or 4 (seen on echo or angiogram)
- •1 New York Heart Association Class 3 or 4
排除标准
- •Patient is participating in another trial
- •Patient has received NAC in the past 48 hours.
- •Patient has allergy to N-acetylcysteine.
- •Patient scheduled for off-pump surgery or an extracardiac procedure (pericardiectomy etc.)
- •Patient requires emergent surgery
- •Patient scheduled for a procedure involving circulatory arrest.
- •Patient requires chronic dialysis (peritoneal or hemodialysis)
- •Patient unable to give informed consent (dementia, does not speak English, etc.)
- •Patient has a recent history of cancer (in last five years) or untreated cancer
结局指标
主要结局
The change in serum creatinine between NAC and placebo groups from preoperative baseline levels to peak postoperative levels after exposure to CPB.
次要结局
- Include change in GFR, BUN and troponin; early dialysis; in-hospital mortality; postop MI; stroke; and postop LOS. SNPs related to renal insufficiency, ischemia, and inflammation will be analyzed in relation to serum inflammatory markers.