Prospective Observational Study Investigating Genomic Determinants of Outcome From Cardiogenic Shock (GOlDilOCS)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- The primary aim is to better understand the heterogeneity of the immune consequences and treatment responses in CS through identification of transcriptomic sub-phenotypes and their association with in-hospital mortality
研究概览
简要总结
The aim of this project is to understand the heterogeneity of both the immune consequences and treatment responses in CS. We will explore this heterogeneity through identification of transcriptomic sub-phenotypes and their association with outcomes, including therapeutic responses.
详细描述
This is a prospective observational cohort study in 8-10 cardiac centres across Europe. We will recruit patients presenting with acute myocardial infarction (AMI) and CS who are supported medically (n=100); with extracorporeal membrane oxygenation (n=50); and with the Impella Device (n=50). We will also enrol patients who present with either AMI and no evidence of CS (n=50) or CS due to non-ischaemic pathologies (e.g. myocarditis: n=50) as comparators. The recruitment target is 300 patients.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All of the following are required for inclusion following screening:
- •Willing to provide informed consent or appropriate consent from a nominated consultee or personal consultee
- •Presentation within 24 hours of onset of ACS symptoms.
- •CS can only be secondary to ACS (Type 1 MI STEMI or N-STEMI) or myocarditis
- •Planned or completed revascularisation of culprit coronary artery
- •CS will be defined by:
- •Systolic blood pressure <90 mmHg for at least 30 minutes
- •A requirement for a continuous infusion of vasopressor or inotropic therapy to maintain systolic blood pressure > 90 mmHg.
- •Clinical signs of pulmonary congestion, plus signs of impaired organ perfusion with at least one of the following manifestations:
- •altered mental status.
- •cold and clammy skin and limbs.
- •oliguria with a urine output of less than 30 ml per hour.
- •elevated arterial lactate level of >2.0 mmol per litre.
排除标准
- •Any of the inclusion criteria not met and:
- •Unwilling to provide informed consent.
- •Echocardiographic evidence (recorded within 90 mins of end of PCI procedure) of mechanical cause for CS: eg ventricular septal defect, LV-free wall rupture, ischaemic mitral regurgitation.
- •Age <18 and ≥80 years.
- •Shock from another cause (sepsis, haemorrhagic/hypovolaemic shock, anaphylaxis, etc).
- •Significant systemic illness
- •Known dementia of any severity
- •Comorbidity with life expectancy <12 months.
- •Out-of-hospital cardiac arrest (OHCA) and any of the following:
- •No return of spontaneous circulation (ongoing resuscitation effort)
- •Without bystander CPR within 10 minutes of collapse
- •Arterial lactate level of <2.0 mmol per litre.
结局指标
主要结局
The primary aim is to better understand the heterogeneity of the immune consequences and treatment responses in CS through identification of transcriptomic sub-phenotypes and their association with in-hospital mortality
时间窗: through study completion, an average of 5 days
This will be achieved through bloods sample collection, analysis and linked to the patient's clinical diagnosis and outcome.
次要结局
- Determine the extent to which the signatures and drivers of a dysfunctional immune response in CS are shared with other critical illness syndromes.(through study completion, an average of 5 days)
- Identify transcriptomic and chemokine/cytokine signatures at presentation that improve prognostic accuracy in patients with CS(through study completion, an average of 5 days)
- Investigate inter-individual heterogeneity in the dynamic transcriptomic response to CS through an eQTL mapping approach and identify context- specific regulatory genetic variants involving gene networks central to the pathogenesis of CS.(through study completion, an average of 5 days)
- Identify transcriptomic (and chemokine/cytokine) signatures at presentation that elucidate the pathobiology of CS and examine their subsequent evolution.(through study completion, an average of 5 days)
- Correlate recently identified clinical phenotypes of CS with transcriptomic and inflammatory mediator signatures.(through study completion, an average of 5 days)
- Identity novel therapeutic targets that might modulate the dysfunctional immune response to CS - "drug discovery"(through study completion, an average of 5 days)