A Phase IIb Multiple Blind Randomized Controlled Trial of Sodium Bicarbonate in Cardiac Surgery at High-risk of Acute Kidney Injury
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 427
- 试验地点
- 4
- 主要终点
- Proportion of patients developing an increase in serum creatinine greater than 25% or 44 mmol/L (0.5 mg/dL) postoperative increase in serum creatinine after adjustment for relevant baseline variables
研究概览
简要总结
With over one million operations a year, cardiac surgery with cardiopulmonary bypass is one of the most common major surgical procedures worldwide (1). Acute kidney injury is a common and serious postoperative complication of cardiopulmonary bypass and may affect 25% to 50% of patients (2-4). Acute kidney injury carries significant costs (4) and is independently associated with increased morbidity and mortality (2,3). Even minimal increments in plasma creatinine are associated with an increase in mortality (5,6).
Multiple causes of cardiopulmonary bypass-associated acute kidney injury have been proposed, including ischemia-reperfusion, generation of reactive oxygen species, hemolysis and activation of inflammatory pathways (7-10). To date, no simple, safe and effective intervention to prevent cardiopulmonary bypass-associated acute kidney injury in a broad patient population has been found (11-14).
Urinary acidity may enhance the generation and toxicity of reactive oxygen species induced by cardiopulmonary bypass (10,15). Activation of complement during cardiac surgery (16) may also participate in kidney injury. Urinary alkalinization may protect from kidney injury induced by oxidant substances, iron-mediated free radical pathways, complement activation and tubular hemoglobin cast formation (9,17,18). Of note, increasing urinary pH - in combination with N-acetylcysteine (19,20) or without (21) - has recently been reported to attenuate acute kidney injury in patients undergoing contrast-media infusion.
In a pilot double-blind, randomized controlled trial the investigators found sodium bicarbonate to be efficacious, safe, inexpensive and easy to administer. These findings now need to be confirmed or refuted by further clinical investigations in other geographic and institutional settings.
Accordingly, the investigators hypothesized that urinary alkalinization might protect kidney function in patients at increased risk of acute kidney injury undergoing cardiopulmonary bypass needs to be confirmed in an international multicenter, double-blind, randomized controlled trial of intravenous sodium bicarbonate.
详细描述
Renal impairment following cardiopulmonary bypass is common. While most of these patients do not require either short or long term renal replacement, the mortality of patients with acute renal failure is substantially greater than those who do not develop renal dysfunction.
In a pilot double-blind, randomized controlled trial we found sodium bicarbonate to be efficacious, safe, inexpensive and easy to administer. These findings now need to be confirmed or refuted by further clinical investigations in other geographic and institutional settings.
There is evidence that sodium bicarbonate affects the cardiovascular, respiratory and immune systems and may be of benefit to patients undergoing cardiac surgery.
Study Design - overview and rationale
Patients will be randomised to receive sodium bicarbonate from the induction of anaesthesia until 24 hours postoperatively, or a placebo (sodium chloride).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 70 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age above 70 years
- •Pre-existing renal impairment (preoperative plasma creatinine concentration > 1.4 mg/dL
- •New York Heart Association class III/IV or impaired left ventricular function (left ventricular ejection fraction < 50%)
- •Valvular surgery or concomitant valvular and coronary artery bypass graft surgery
- •Redo cardiac surgery
- •Insulin-dependent diabetes mellitus
排除标准
- •End stage renal disease (plasma creatinine concentration > 3.4 mg/dL)
- •Emergency cardiac surgery
- •Planned off-pump cardiac surgery
- •Known blood-borne infectious disease
- •Chronic inflammatory disease on immunosuppression
- •Chronic moderate to high dose corticosteroid therapy (> 10 mg/d prednisone or equivalent)
- •Enrolled in conflicting research study
- •Age < 18 years
研究组 & 干预措施
1
In all patients body weight adjusted dose of study medication will be achieved by infusion of sodium bicarbonate at a dose of 0.5 mmol/kg body weight (=bolus) diluted in 250 mL over 1 hour immediately after the induction of anesthesia, prior to the first surgical incision followed by continuous intravenous infusion of 0.2 mmol/kg/hr (=maintenance) diluted in 1000 mL 23 hours (total dose of 5 mmol/kg over 24 hours).
干预措施: Sodium Bicarbonate (Drug)
2
In all patients body weight adjusted dose of study medication will be achieved by infusion of sodium chloride at a dose of 0.5 mmol/kg body weight (=bolus) diluted in 250 mL over 1 hour immediately after the induction of anesthesia, prior to the first surgical incision followed by continuous intravenous infusion of 0.2 mmol/kg/hr (=maintenance) diluted in 1000 mL 23 hours (total dose of 5 mmol/kg over 24 hours).
干预措施: Sodium Chloride (Drug)
结局指标
主要结局
Proportion of patients developing an increase in serum creatinine greater than 25% or 44 mmol/L (0.5 mg/dL) postoperative increase in serum creatinine after adjustment for relevant baseline variables
时间窗: within first five postoperative days
次要结局
- Change in electrolyte status from baseline to peak(within first 24-48hrs postoperatively)
- Mean changes in serum creatinine after adjustment for relevant baseline variables(within first five postoperative days)
- mean changes in serum cystatin C after adjustment for relevant baseline variables(within first five postoperative days)
- mean changes in urinary neutrophil gelatinase-associated lipocalin (NGAL)after adjustment for relevant baseline variables(within first five postoperative days)
- Duration of ventilation(Until time of extubation from mechanical ventilation)
- Proportion of patients developing any of the RIFLE criteria: R, I or F(within first five postoperative days)
- Incidence of post-operative atrial fibrillation(within first five postoperative days)
- Duration of stay in the intensive care unit (ICU)(from admission to the ICU)
- Duration of stay in hospital(from admission to discharge from hospital)
- 90-day mortality(during 90 days postoperatively)
研究者
Rinaldo Bellomo
Director of ICU Research
Austin Health