Clinical trial NCT05728359: Genomic Determinants of Outcome in Cardiogenic Shock
Official title: Prospective Observational Study Investigating Genomic Determinants of Outcome From Cardiogenic Shock (GOlDilOCS)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cardiogenic Shock
Keywords: ACS,
Cardiogenic Shock
ECMO
Impella
Gene Expression
Endotype
Lead sponsor: Barts & The London NHS Trust
Sponsor class: OTHER
Collaborators: name: University of Oxford
First posted: 2023-02-15
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All patients presenting to recruiting sites who fulfil study inclusion criteria and have no exclusion, will be considered. The majority of patients will be present through the heart attack centres and pathways. Some patients will, however, develop cardiogenic shock (CS) during their admission. These patients will be recruited from the coronary care units, intensive care units or cardiology wards and will be identified by clinicians who will alert research staff.

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.

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.
  * 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:

  1. Unwilling to provide informed consent.
  2. 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.
  3. Age \<18 and ≥80 years.
  4. Shock from another cause (sepsis, haemorrhagic/hypovolaemic shock, anaphylaxis, etc).
  5. Significant systemic illness
  6. Known dementia of any severity
  7. Comorbidity with life expectancy \<12 months.
  8. Out-of-hospital cardiac arrest (OHCA) and any of the following:

     1. No return of spontaneous circulation (ongoing resuscitation effort)
     2. pH \<7
     3. Without bystander CPR within 10 minutes of collapse
  9. Arterial lactate level of \<2.0 mmol per litre.

Primary outcomes:
measure: 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
timeFrame: through study completion, an average of 5 days
Secondary outcomes:
measure: Identify transcriptomic (and chemokine/cytokine) signatures at presentation that elucidate the pathobiology of CS and examine their subsequent evolution.
timeFrame: through study completion, an average of 5 days
measure: Correlate recently identified clinical phenotypes of CS with transcriptomic and inflammatory mediator signatures.
timeFrame: through study completion, an average of 5 days
measure: Identify transcriptomic and chemokine/cytokine signatures at presentation that improve prognostic accuracy in patients with CS
timeFrame: through study completion, an average of 5 days
measure: 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.
timeFrame: through study completion, an average of 5 days
measure: Identity novel therapeutic targets that might modulate the dysfunctional immune response to CS - "drug discovery"
timeFrame: through study completion, an average of 5 days
measure: Determine the extent to which the signatures and drivers of a dysfunctional immune response in CS are shared with other critical illness syndromes.
timeFrame: through study completion, an average of 5 days
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Barts Health NHS trust
Study officials:
affiliation: Barts Heath NHS trust
name: Alastair Proudfoot
role: PRINCIPAL_INVESTIGATOR
References:
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