Interleukin-6 Receptor Antibodies for Modulating the Systemic Inflammatory Response After Out-of-Hospital Cardiac Arrest - a Randomized Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Concentration of hsCRP
研究概览
简要总结
Resuscitated cardiac arrest is associated with a systemic inflammatory response that is directly associated with poor prognosis. Inhibition of the IL-6 mediated immune response may potentially inhibit the systemic inflammatory response, potentially improving the prognosis of these severely ill patients.
详细描述
INTRODUCTION AND BACKGROUND:
The incidence of out-of-hospital cardiac arrest (OHCA) in Denmark is approximately 4,000 per year, and the mortality remains approximately 90%. Furthermore, in the approximately 30% of patients who are resuscitated and admitted to the intensive care unit (ICU), the mortality within the first month remains between 50% to 70%. Accordingly, an increasing emphasis on post-resuscitation care has been addressed by contemporary guidelines.
The high mortality after resuscitated OHCA has been attributed to a post-cardiac arrest syndrome (PCAS), which includes four mutually interacting components: a systemic inflammatory response (SIRS)-like syndrome, cerebral injury, myocardial dysfunction, and the persistent precipitating cause of the arrest. Despite repeated emphasis on post-resuscitation care, no specific therapies targeting PCAS have been implemented, with the exception of targeted temperature management (TTM), which has been recommended since 2003. Accordingly, research addressing mitigation of the PCAS seems intuitively beneficial.
During and after OHCA, exposure to whole-body ischemia and reperfusion injury triggers activation of inflammatory cascades leading to a sepsis-like syndrome. A multitude of inflammatory markers have been associated with unfavorable outcome after OHCA, including procalcitonin (PCT), c-reactive protein (CRP), interleukin (IL) 6, and IL-10.
Furthermore, the inflammatory markers interleukin 1β (IL-1β), IL-6, IL-10, and tumor necrosis factor α (TNF-α) have all been associated with the severity of PCAS, assessed by sequential organ failure assessment (SOFA) score. Importantly, levels of IL-6 have been shown to be independently associated with unfavorable outcome after adjustment for known risk markers. Further, the level of IL-6 was more strongly associated with PCAS severity compared to classical inflammatory markers such as CRP and PCT.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Each of the following criteria must be fulfilled for a subject to be eligible:
- •Age ≥ 18 years
- •OHCA of a presumed cardiac cause
- •Unconsciousness upon admission, i.e. a GCS < 9
- •Sustained ROSC for more than 20 minutes
排除标准
- •None of the following criteria must be fulfilled for a subject to be eligible:
- •Consciousness upon admission, i.e. a GCS ≥ 9
- •Presumed non-cardiac cause of arrest
- •Unwitnessed asystole
- •Suspected or confirmed intracranial bleeding or stroke
- •Pregnancy, or females in fertile age, unless a negative serum HCG can rule out pregnancy within the inclusion window.
- •Temperature on admission < 30 °C
- •Persistent cardiogenic shock* that is not reversed within the inclusion window
- •Known disease making 180 day survival unlikely
- •Known limitations in therapy
- •Known pre-arrest Cerebral Performance Category of 3 to 4
- •> 240 minutes from ROSC to randomization
研究组 & 干预措施
Tocilizumab
A one hour infusion of a single 8mg/kg dose (max. 800mg) of tocilizumab to attenuate systemic inflammation after out-of-hospital cardiac arrest, given as early as possible after hospital admission.
干预措施: Tocilizumab 20 Mg/mL Intravenous Solution (Drug)
Isotonic saline
A one hour infusion of isotonic saline
干预措施: isotonic saline (Drug)
结局指标
主要结局
Concentration of hsCRP
时间窗: Daily measurements from admission to 72 hours after admission.
high sensitivity C-reactive protein
次要结局
- Markers of hemodynamic function, Swan-Ganz Catheter(At admission, 24h, 48h & 72h)
- Markers of hemodynamic function, Arterial blood gasses(At admission, 2h, 4h, 6h, 8h, 10h, 12h, 18h, 24h, 30h, 36h, 48h, 72h, 96h and 120h (sampling ceases if the arterial line is discontinued).)
- Markers of inflammation, interleukin levels(At admission, 24h, 48h & 72h)
- Biomarkers of organ damage(Plasma/serum samples and routine biochemistry are collected at admission, 24h, 48h and 72h (NSE only at 48 and 72h))
- Markers of inflammation, leukocytes(At admission, 24h, 48h & 72h)
- Markers of hemodynamic function, Echocardiography(Day 1 and on either day 3, 4 or 5.)
- Markers of inflammation, SOFA score(The first 3 days from admission)
- Markers of the coagulation system, fibrinogen(At admission, 48h and 72h)
- Clinical endpoints, MOCA score(At 90 days.)
- Clinical endpoints, CPC(At 30 days, 90 days and 180 days.)
- Safety: incidence of adverse events(From admission till 7 days.)
- Markers of the coagulation system, thrombelastography(At admission and 48h)
- Clinical endpoints, Survival(At 30 days, 90 days, 180 days, and at end of trial.)
研究者
Christian Hassager
Professor, MD, DMSc, FESC
Rigshospitalet, Denmark