HYdrocortisone and VAsopressin in Post-REsuscitation Syndrome
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 380
- 试验地点
- 14
- 主要终点
- Neurological outcome
研究概览
简要总结
The primary objective is to demonstrate the superiority of arginine-vasopressin (AVP) and hydrocortisone compared with norepinephrine regarding day-30 survival and neurological recovery in post-cardiac arrest patients with hemodynamic failure.
详细描述
For patients successfully resuscitated who got restoration of spontaneous circulation (ROSC) after cardiopulmonary resuscitation (CPR), the course is usually marked by a post-resuscitation syndrome including multiple organ failures of various intensity and anoxic brain damage. The cardiocirculatory failure usually dominates the clinical picture, and it often leads to multiorgan failure. This hemodynamic failure is multifactorial, including at various levels vasoplegia, myocardial dysfunction, endotoxin release and adrenal dysfunction and is at least partly related to a hormonal defect that could be counteracted by hormonal supplementation. Such a substitutive opotherapy by hydrocortisone and AVP could improve hemodynamic failure and decrease overall mortality in this setting.
This trial is a superiority multicentric trial and patients will be randomized in a 1:1:1:1 ratio using an electronic CRF.
Investigational medicinal products:
- Arginin-vasopressin or AVP (REVERPLEG) The solution for infusion is prepared by diluting 40 I.U. REVERPLEG® with sodium chloride 9 mg/ml (0.9%) solution. The total volume after dilution should be 50 ml (equivalent to 0.8 I.U. AVP per ml).
AVP will be administered according to mean arterial pressure to target a 65mmHg blood pressure for max 3 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 patients (>18y)
- •Cardiac arrest (in-hospital or out-of-hospital) with sustained ROSC (> 30 minutes) admitted to the ICU
- •Post-resuscitation shock defined as arterial hypotension (SAP < 90 mmHg or MAP < 65 mmHg) unresponsive to adequate fluid loading, which occurred within the first 24 hours after ROSC and requiring norepinephrine/epinephrine continuous infusion at a dose greater or equal to 0.2µg/kg/min for at least 3 hours
- •A maximal delay between the start of norepinephrine infusion and randomization of 9 hours
- •Informed written consent of the patient or a legally authorized close relative.
排除标准
- •Evidence for a traumatic or a neurological cause of cardiac arrest
- •Shock due to uncontrolled haemorrhage
- •Previously known adrenal insufficiency
- •Limitation of life-sustaining therapies
- •Ongoing treatment by any steroids, whatever the dose
- •Ongoing extra-corporeal circulatory assistance
- •Gastrointestinal bleeding in the past 6 weeks
- •Pregnant or breastfeeding women
- •Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants, if applicable
- •Hypersensitivity to arginin-vasopressin and to its excipients
- •Hypersensitivity to hydrocortisone and to its excipients
- •Legal protection (i.e. incompetence to provide consent, guardianship, curator or incarceration)
- •No affiliation with the French health care system.
研究组 & 干预措施
AVP + placebo hydrocortisone
REVERPLEG® 40 IU/2mL+ Placebo of hydrocortisone.
干预措施: Administration of AVP (Drug)
placebo AVP + placebo hydrocortisone
Placebo of REVERPLEG® 40 IU/2mL + placebo of hydrocortisone
干预措施: Administration of placebo hydrocortisone (Drug)
AVP + placebo hydrocortisone
REVERPLEG® 40 IU/2mL+ Placebo of hydrocortisone.
干预措施: Administration of placebo hydrocortisone (Drug)
placebo AVP + hydrocortisone
Placebo of REVERPLEG® 40 IU/2mL + Hydrocortisone 100mg UPJOHN®.
干预措施: Administration of placebo AVP (Drug)
placebo AVP + hydrocortisone
Placebo of REVERPLEG® 40 IU/2mL + Hydrocortisone 100mg UPJOHN®.
干预措施: Administration of hydrocortisone (Drug)
AVP + hydrocortisone
REVERPLEG® 40 IU/2mL + Hydrocortisone 100mg UPJOHN®.
干预措施: Administration of AVP (Drug)
AVP + hydrocortisone
REVERPLEG® 40 IU/2mL + Hydrocortisone 100mg UPJOHN®.
干预措施: Administration of hydrocortisone (Drug)
placebo AVP + placebo hydrocortisone
Placebo of REVERPLEG® 40 IU/2mL + placebo of hydrocortisone
干预措施: Administration of placebo AVP (Drug)
结局指标
主要结局
Neurological outcome
时间窗: at day-30
The primary endpoint will be the good neurological outcome at day-30. This will be evaluated using the Glasgow Outcome Scale (GOS, addendum 18.5.1) dichotomized as follow: good neurological outcome for categories 4 and 5 and poor neurological outcome or death for categories 3, 2 and 1. The GOS will be obtained at day-30 from an in-hospital visit if the patient is still hospitalized or from telephone contact with patients, relatives or general practitioners.
次要结局
- All-cause mortality(at day-30)
- Mortality attributed to irreversible hemodynamic failure(at day-30)
- Brain damage(at 48 hours and at 72hours)
- mortality attributed to recurrent cardiac arrest(at day-30)
- Mortality attributed to comorbid withdrawal of care(at day-30)
- Other causes(at day-30)
- Neurological recovery at day-30(at day-30)
- Mortality attributed to neurological withdrawal of care(at day-30)
- Day-30 brain death(at day-30)