Genomic Determinants of Outcome in Cardiogenic Shock

Cardiogenic Shock Clinical Trial

— Goldilocs  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05728359
• Other study ID #: 290406
• Status: Recruiting
• Start date: September 20, 2022
• Est. completion date: July 1, 2025

Study information

• Verified date: July 2022
• Source: Barts & The London NHS Trust
• Contact: Alastair Proudfoot
• Phone: 02037658707
• Email: alastair.proudfoot1[@]nhs.net
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: July 1, 2025
• Est. primary completion date: July 1, 2025
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiogenic Shock
• Shock
• Shock, Cardiogenic

Intervention

Other:
• Observational study
Blood sampling and clinical data collection

Locations

Country	Name	City	State
United Kingdom	Barts Health NHS trust	London

Sponsors (2)

Lead Sponsor	Collaborator
Barts & The London NHS Trust	University of Oxford

Country where clinical trial is conducted

United Kingdom, 

References & Publications (4)

Cano-Gamez E, Burnham KL, Goh C, Allcock A, Malick ZH, Overend L, Kwok A, Smith DA, Peters-Sengers H, Antcliffe D; GAinS Investigators; McKechnie S, Scicluna BP, van der Poll T, Gordon AC, Hinds CJ, Davenport EE, Knight JC, Webster N, Galley H, Taylor J, Hall S, Addison J, Roughton S, Tennant H, Guleri A, Waddington N, Arawwawala D, Durcan J, Short A, Swan K, Williams S, Smolen S, Mitchell-Inwang C, Gordon T, Errington E, Templeton M, Venatesh P, Ward G, McCauley M, Baudouin S, Higham C, Soar J, Grier S, Hall E, Brett S, Kitson D, Wilson R, Mountford L, Moreno J, Hall P, Hewlett J, McKechnie S, Garrard C, Millo J, Young D, Hutton P, Parsons P, Smiths A, Faras-Arraya R, Soar J, Raymode P, Thompson J, Bowrey S, Kazembe S, Rich N, Andreou P, Hales D, Roberts E, Fletcher S, Rosbergen M, Glister G, Cuesta JM, Bion J, Millar J, Perry EJ, Willis H, Mitchell N, Ruel S, Carrera R, Wilde J, Nilson A, Lees S, Kapila A, Jacques N, Atkinson J, Brown A, Prowse H, Krige A, Bland M, Bullock L, Harrison D, Mills G, Humphreys J, Armitage K, Laha S, Baldwin J, Walsh A, Doherty N, Drage S, Ortiz-Ruiz de Gordoa L, Lowes S, Higham C, Walsh H, Calder V, Swan C, Payne H, Higgins D, Andrews S, Mappleback S, Hind C, Garrard C, Watson D, McLees E, Purdy A, Stotz M, Ochelli-Okpue A, Bonner S, Whitehead I, Hugil K, Goodridge V, Cawthor L, Kuper M, Pahary S, Bellingan G, Marshall R, Montgomery H, Ryu JH, Bercades G, Boluda S, Bentley A, Mccalman K, Jefferies F, Knight J, Davenport E, Burnham K, Maugeri N, Radhakrishnan J, Mi Y, Allcock A, Goh C. An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression. Sci Transl Med. 2022 Nov 2;14(669):eabq4433. doi: 10.1126/scitranslmed.abq4433. Epub 2022 Nov 2. — View Citation

Davenport EE, Burnham KL, Radhakrishnan J, Humburg P, Hutton P, Mills TC, Rautanen A, Gordon AC, Garrard C, Hill AV, Hinds CJ, Knight JC. Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study. Lancet Respir Med. 2016 Apr;4(4):259-71. doi: 10.1016/S2213-2600(16)00046-1. Epub 2016 Feb 23. — View Citation

Maslove DM, Tang B, Shankar-Hari M, Lawler PR, Angus DC, Baillie JK, Baron RM, Bauer M, Buchman TG, Calfee CS, Dos Santos CC, Giamarellos-Bourboulis EJ, Gordon AC, Kellum JA, Knight JC, Leligdowicz A, McAuley DF, McLean AS, Menon DK, Meyer NJ, Moldawer LL, Reddy K, Reilly JP, Russell JA, Sevransky JE, Seymour CW, Shapiro NI, Singer M, Summers C, Sweeney TE, Thompson BT, van der Poll T, Venkatesh B, Walley KR, Walsh TS, Ware LB, Wong HR, Zador ZE, Marshall JC. Redefining critical illness. Nat Med. 2022 Jun;28(6):1141-1148. doi: 10.1038/s41591-022-01843-x. Epub 2022 Jun 17. — View Citation

Toma A, Dos Santos C, Burzynska B, Gora M, Kiliszek M, Stickle N, Kirsten H, Kosyakovsky LB, Wang B, van Diepen S, Epelman S, Szekely Y, Marshall JC, Billia F, Lawler PR. Diversity in the Expressed Genomic Host Response to Myocardial Infarction. Circ Res. 2022 Jun 24;131(1):106-108. doi: 10.1161/CIRCRESAHA.121.318391. Epub 2022 May 9. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	This will be achieved through bloods sample collection, analysis and linked to the patient's clinical diagnosis and outcome.	through study completion, an average of 5 days
Secondary	Identify transcriptomic (and chemokine/cytokine) signatures at presentation that elucidate the pathobiology of CS and examine their subsequent evolution.	Bloods samples will be collected from patients during their hospital stay and corresponding analysis performed.	through study completion, an average of 5 days
Secondary	Correlate recently identified clinical phenotypes of CS with transcriptomic and inflammatory mediator signatures.	Bloods samples will be collected from patients during their hospital stay and corresponding analysis performed.	through study completion, an average of 5 days
Secondary	Identify transcriptomic and chemokine/cytokine signatures at presentation that improve prognostic accuracy in patients with CS	Bloods samples will be collected from patients during their hospital stay and corresponding analysis performed.	through study completion, an average of 5 days
Secondary	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.	Bloods samples will be collected from patients during their hospital stay and corresponding analysis performed.	through study completion, an average of 5 days
Secondary	Identity novel therapeutic targets that might modulate the dysfunctional immune response to CS - "drug discovery"	Bloods samples will be collected from patients during their hospital stay and corresponding analysis performed.	through study completion, an average of 5 days
Secondary	Determine the extent to which the signatures and drivers of a dysfunctional immune response in CS are shared with other critical illness syndromes.	Bloods samples will be collected from patients during their hospital stay and corresponding analysis performed.	through study completion, an average of 5 days