Prospective Observational Study Investigating Genomic Determinants of Outcome From Cardiogenic Shock (GOlDilOCS)
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Cardiogenic Shock
- Sponsor
- Barts & The London NHS Trust
- Enrollment
- 300
- Locations
- 1
- Primary Endpoint
- 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
- Status
- Recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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)
Outcomes
Primary Outcomes
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
Time Frame: 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.
Secondary Outcomes
- 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)