Conservative vs. Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care (CLASSIC) - a Randomised Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 153
- 试验地点
- 9
- 主要终点
- Resuscitation volume
研究概览
简要总结
The purpose of this trial is to o assess feasibility of a protocol comparing conservative (trigger guided) vs. liberal (target guided) approach to fluid resuscitation in patients with septic shock after initial fluid resuscitation.
详细描述
Fluid resuscitation is a key intervention in treatment of sepsis, but exact indications for fluid and amount of fluid administered is not established. Current guidelines for fluid therapy beyond 6 hours are vague and ungraded and most observational studies suggest harm with increasing positive fluid balance.
Objective To assess feasibility of a protocol comparing a conservative (trigger guided) vs. liberal (target guided) approach to fluid resuscitation in patients with septic shock after initial fluid resuscitation.
Design Multicentre, parallel group, centrally randomised, open label trial with adequate generation of allocation sequence, and adequate allocation concealment.
Sample size 150 included patients we will be needed to show a 1.7 L difference in fluid volumes between the groups based on the mean volume of resuscitation fluid given within first 5 days observed in the 6S trial of 5.3 L (SD 3.7 L) with a maximal type 1 and 2 error of 5% and 20% (power=80%), respectively.
Funding The trial is publicly funded by the Danish Council for Strategic Research
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult intensive care patients (age ≥ 18 years) with sepsis defined as 2 of 4 SIRS criteria fulfilled within 24 hours and suspected or confirmed site of infection or positive blood culture.
- •Suspected or confirmed circulatory impairment (hypotension/hypoperfusion/hypovolemia) for no more than 12 hours including the hours preceding ICU admission.
- •At least 30 ml/kg ideal body weight (IBW) fluid (colloids, crystalloids or blood products) given in the last 6 hours.
- •Shock defined as ongoing infusion of norepinephrine (any dose) to maintain blood pressure.
排除标准
- •Use of any form of renal replacement therapy (RRT).
- •RRT deemed imminent by the ICU doctor, i.e. RRT will be initiated within 6 hours.
- •Severe hyperkalemia (p-K > 6 mM).
- •Plasma creatinine > 350 µmol/l.
- •Invasively ventilated with FiO2 > 0.80 and PEEP > 10 cmH2O
- •Life-threatening bleeding.
- •Kidney or liver transplant during current admission.
- •Burns > 10% body surface area (BSA).
- •Previously enrolled in the CLASSIC trial and has finished the 90 day observation period.
- •Patients for whom it has been decided not to give full life support including mechanical ventilation and RRT.
- •Consent not obtainable.
研究组 & 干预措施
Liberal (target-guided) fluid resuscitation
Noradrenaline to MAP >= 65 mmHg.
Fluid boluses may be given as long as hemodynamic variables improve (dynamic or static variable(s) of choice). A fluid bolus is to be followed by evaluation of effect 30 minutes after the intervention at the latest.
'Variable(s) of choice' refers to the variable(s) used to assess hemodynamic improvement.
Only isotonic crystalloids are to be given as resuscitation fluid; the type of isotonic crystalloid is free of choice.
干预措施: Isotonic crystalloids (Drug)
Conservative (trigger-guided) fluid resuscitation
Noradrenaline to MAP >= 65 mmHg.
A fluid bolus of 250-500 ml may be given followed by evaluation of effect 30 minutes after the intervention at the latest if one of the following occurs:
- Plasma lactate concentration ≥ 4 mmol/l at point-of-care testing.
- Severe hypotension (MAP < 50mmHg).
- Mottling beyond edge of kneecap.
- Severe oliguria (only in the first 2 hours after randomisation). Severe oliguria defined as urine output ≤ 0.1 ml/kg/hour IBW last hour.
Only isotonic crystalloids are to be given as resuscitation fluid; the type of isotonic crystalloid is free of choice.
干预措施: Isotonic crystalloids (Drug)
结局指标
主要结局
Resuscitation volume
时间窗: Followed up until ICU discharge; an expected average of one week
次要结局
- Total fluid input(Followed up until ICU discharge; an expected average of one week)
- Number of patients with protocol violations(Followed up until ICU discharge; an expected average of one week)
- Fluid balance(Followed up until ICU discharge; an expected average of one week)
- Accumulated serious adverse reactions (SARs)(Followed up until ICU discharge; an expected average of one week)
研究者
Anders Perner
Chair
Scandinavian Critical Care Trials Group