Goldilocs: Genomic Determinants of Outcome in Cardiogenic Shock

Sponsor

Barts & The London NHS Trust (Other)

Overall Status

Recruiting

CT.gov ID

NCT05728359

Collaborator

University of Oxford (Other)

300

Enrollment

Location

33.3

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiogenic Shock	Other: Observational study

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.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

300 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Prospective Observational Study Investigating Genomic Determinants of Outcome From Cardiogenic Shock (GOlDilOCS)

Actual Study Start Date :

Sep 20, 2022

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Cardiogenic shock and MI Patients presenting with acute myocardial infarction and cardiogenic shock who are supported medically (ie. inotropes +/- intra aortic balloon pump only). N=50	Other: Observational study Blood sampling and clinical data collection
Cardiogenic shock and MI wtih ECMO Patients presenting with acute myocardial infarction and cardiogenic shock who are supported medically with ECMO (+/- LV unloading device). N=50	Other: Observational study Blood sampling and clinical data collection
Cardiogenic shock and MI wtih Impella Patients presenting with acute myocardial infarction and cardiogenic shock who are supported medically with Impella. N=50	Other: Observational study Blood sampling and clinical data collection
MI without cardiogenic shock Patients presenting with acute myocardial infarction and cardiogenic shock as a control comparator	Other: Observational study Blood sampling and clinical data collection
Non ischemic Cardiogenic Shock ie myocarditis Patients presenting with myocarditis and cardiogenic shock as a control comparator	Other: Observational study Blood sampling and clinical data collection

Outcome Measures

Primary Outcome Measures

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 [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 Outcome Measures

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]
Bloods samples will be collected from patients during their hospital stay and corresponding analysis performed.
Correlate recently identified clinical phenotypes of CS with transcriptomic and inflammatory mediator signatures. [through study completion, an average of 5 days]
Bloods samples will be collected from patients during their hospital stay and corresponding analysis performed.
Identify transcriptomic and chemokine/cytokine signatures at presentation that improve prognostic accuracy in patients with CS [through study completion, an average of 5 days]
Bloods samples will be collected from patients during their hospital stay and corresponding analysis performed.
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]
Bloods samples will be collected from patients during their hospital stay and corresponding analysis performed.
Identity novel therapeutic targets that might modulate the dysfunctional immune response to CS - "drug discovery" [through study completion, an average of 5 days]
Bloods samples will be collected from patients during their hospital stay and corresponding analysis performed.
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]
Bloods samples will be collected from patients during their hospital stay and corresponding analysis performed.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

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.
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.

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)
pH <7
Without bystander CPR within 10 minutes of collapse
Arterial lactate level of <2.0 mmol per litre.