Phase III of Recombinant Human Activated Protein C and Low Dose of Hydrocortisone and Fludrocortisone in Adult Septic Shock
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,241
- 试验地点
- 4
- 主要终点
- 90-day mortality
研究概览
简要总结
This study aims at comparing the efficacy and safety of recombinant human activated protein C to that of low dose of corticosteroids and at investigating the interaction between these drugs in the management of septic shock
详细描述
Septic shock still places a burden in the healthcare system round around the world. In the early 20ties, clinical trials suggested potential benefits from activated protein C in severe sepsis and of corticosteroids when given to adults with refractory shock. More recent studies suggested that patients with moderate sepsis or septic shock may not benefit from either activated protein C or corticosteroids. Therefore, current international guidelines suggest that physicians may consider using these drugs in the more severe cases of sepsis. The main risk associated with the use of activated protein C is bleeding and the main risk associated with the use of steroids is superinfection. It is paramount that a new adequately powered trial explores the benefit/risk ratio of these two drugs and of their combination in a population of adult patients with septic shock.
After the withdrawal of Xigris in October 2011, the study was suspended and restarted in June 2012 to investigate the benefit to risk ratio of corticosteroids.
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
- •hospitalized in intensive care unit for less than 7 days
- •septic shock for less than 24 hours
- •at least one proven site of infection
- •at least 2 organ dysfunction as defined by a SOFA score =or> to 3 for at least 6 consecutive hours
- •need for vasopressor (dopamine =or>15µg/kg/min or epinephrine/norepinephrine at =or>0,25 µg/kg/min for at least 6 consecutive hours, to maintain systolic arterial pressure at 90 mmHg or more OR mean arterial pressure at 6( mmHg or more
- •informed consent
排除标准
- •pregnancy or breath feeding
- •decision not to resuscitate
- •underlying disease with an estimated life expectancy of less than 1 month
- •formal indication for corticosteroids
- •recent surgery (ie within the past 72 hours) or a surgery at high risk of bleeding
- •gastro-intestinal bleeding within the past 6 weeks
- •chronic liver disease (Child C)
- •recent trauma (ie within the past 72 hours)
- •intracranial process
- •history of stroke, CNS bleeding or traumatic brain injury within the past 3 months
- •platelet counts of less than 30000 per cubic millimeter
- •formal indication for curative anticoagulant; prophylactic use of heparin is allowed
- •any condition of high risk of bleeding as per patient's primary physicians
- •hypersensitivity of activated drotrecogin alpha or any other component of the drug
- •no affiliation to a social security
- •Amendments to eligibility criteria were:
- •On 27/03/2008: Changes in following exclusion criteria :
- •"surgical procedure in the past 7 days" was changed for "surgical procedure within 72 hours, or any surgery associated with high risk of bleeding, or a planned surgery within 24 h".
- •"chronic liver disease" was clarified as "chronic liver disease with Child score C".
- •"severe thrombopenia" was clarified "as severe thrombopenia (<30,000/mm3, before transfusion).
- •On 25/08/2009: The exclusion criteria: surgical procedure within 72 hours, or any surgery associated with high risk of bleeding, or a planned surgery within 24 h" was changed for "surgical procedure within 12 hours, or any surgery associated with high risk of bleeding
- •On 11/06/2010: the inclusion criteria: admitted to the ICU for < 7 days was removed; and a new exclusion criteria was added: "patients who had a previous episode of sepsis during the same hospital stay
- •On 18/04/2012: following the withdrawal of DAA from the market: the following exclusion criteria (only related to DAA) were removed :
- •any surgery in the past 12 hours, or any surgery associated with high risk of bleeding;
- •chronic liver disease with a Child score C;
- •recent trauma;
- •any intracranial mass, or stroke or head injury in the past 3 months;
- •severe thrombocytopenia (< 30.000 /mm3, before platelet transfusion);
- •formal indication for anticoagulation, or any other condition associated with increased risk of bleeding, as appreciated by the patient's physician.
研究组 & 干预措施
1
placebo of hydrocortisone, placebo of fludrocortisone and placebo of activated protein C
干预措施: placebos (Drug)
2
Hydrocortisone plus fludrocortisone and a placebo of activated protein C
干预措施: hydrocortisone and fludrocortisone and placebo (Drug)
3
placebo of hydrocortisone, placebo of fludrocortisone and activated protein C
干预措施: recombinant human activated protein C and placebos (Drug)
4
hydrocortisone plus fludrocortisone plus activated protein C
干预措施: recombinant human activated protein C and hydrocortisone and fludrocortisone (Drug)
结局指标
主要结局
90-day mortality
时间窗: 90 day
次要结局
- time to achieve an SOFA score of less than 6(up to 90 days)
- number of days alive and free of vasopressor therapy(up to 90 days)
- number of days alive with a SOFA score < 6 points(up to 90 days)
- time to wean mechanical ventilation(up to 90 days)
- number of days alive and free of mechanical ventilation(up to 90 days)
- Length of intensive care unit and hospital stay(up to hospital discharge)
- acquisition of new infection(up to 180 days)
- new episode of sepsis(up to 90 days)
- new episode of septic shock(up to 90 days)
- bleeding events(up to 90 days)
- neurological sequels at intensive care unit and at hospital discharge and at 90 and 180 days(up to 6 months)
- mortality at 6 months(6 months)
- Time to wean vasopressor therapy(up to 90 days)
- mortality at 28 day(28-day)
- mortality at ICU discharge(ICU discharge)
- mortality at hospital discharge(hospital discharge)
- decision to withhold or withdraw active treatments(up to 90 days)
研究者
Djillali Annane
Professor in medicine
University of Versailles