Clinical trial NCT03813134: Testing the Value of Novel Strategy and Its Cost Efficacy in Order to Improve the Poor Outcomes in Cardiogenic Shock
Official title: EURO SHOCK Testing the Value of Novel Strategy and Its Cost Efficacy in Order to Improve the Poor Outcomes in Cardiogenic Shock
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cardiogenic Shock
Keywords: Cardiogenic Shock
Acute Myocardial Infarction
Acute Coronary Syndrome
Lead sponsor: University of Leicester
Sponsor class: OTHER
Collaborators: name: European Commission
name: University of Glasgow
name: KU Leuven
name: University of East Anglia
name: Deutsches Herzzentrum Muenchen
name: A.O. Ospedale Papa Giovanni XXIII
name: Chalice Medical Ltd
name: Ludwig-Maximilians - University of Munich
name: University of Tromso
name: Institut d'Investigacions Biomèdiques August Pi i Sunyer
name: Paula Stradina Liniska Universitates
name: Accelopment AG
name: Universiteit Antwerpen
name: European Cardiovascular Research Center
First posted: 2019-01-23
Enrollment: 428
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, open, multicentre, randomised strategy trial in Cardiogenic Shock (CGS)
Primary purpose: TREATMENT

Brief summary: Cardiogenic shock (CGS) affects up to 10% of patients suffering acute coronary syndrome. It has a 30 day mortality of 45-50%. No pharmacological nor intervention/device trials have had any impact on this mortality in the last 20 years.

The EURO SHOCK Trial (supported by the European Union Horizons 2020 programme) will randomise 428 patients with CGS following acute coronary syndrome from 44 EU centres to early intervention with Extra Corporeal Membrane Oxygenation (ECMO) therapy or to standard treatment (with no ECMO). This intervention is a high cost specialist centre procedure that warrants further investigation including economic appraisal. Multiple mechanistic and hypothesis generating sub-studies will be undertaken.

Detailed description: The EURO SHOCK trial tests the novel use of early deployment of mechanical support device in Cardiogenic Shock (CGS) in a randomised, strategy trial, with evidence of benefit or otherwise measured by recording hard clinical end-point outcomes.

Extra Corporeal Membrane Oxygenation (ECMO) is already used in CGS. This is therefore not a novel therapy. It is the use of ECMO early in the development of CGS that is the novel aspect of this project. The Investigators will test whether a strategy of very early ECMO can ameliorate the rapid decline that many CGS patients suffer. The value of deploying a clinically used and approved device prospectively and early in the natural history of CGS compared to standard practice has not been tested before and will be the basis of the EURO SHOCK project.

This trial itself will be a prospective randomized, open label, design study that will compare two groups of patients: Both will receive appropriate percutaneous coronary intervention (PCI) as is current practice as they arrive at the hospital.

1. Group 1 will receive immediate PCI + standard care (pharmacological support).
2. Group 2 will receive immediate PCI plus support with early peripheral veno-arterial ECMO + standard care (pharmacological support).

The Investigators will also compare the cost-effectiveness of early VA-ECMO, as compared to current standard of care. EURO SHOCK will also evaluate novel CMR protocols in these unwell patients, and also whether systems of urgent flagged transfer of the unwell patient is practical and beneficial. The Investigators will determine whether there are biological and ECG markers that predict worse patient outcomes, which could thus help select most appropriate patients for expedited treatments (the patient is only transferred if needed).

Although at the centre of the project there is a randomised trial, other important objectives will therefore be delivered.

The research study will additionally focus, through a-priori, post-hoc analyses, on higher risk and vulnerable sub groups such as the elderly (\>75 years) and females, the importance of site of infarct and on those with multi-morbidities such as diabetes. These post-hoc data will be published separately.

The trial will include patients with out of hospital cardiac arrest (OHCA) who have documented return of spontaneous circulation (ROSC) but with certain caveats (see exclusion criteria).

The primary outcome is the all-cause mortality at 30 days following admission with acute coronary syndrome with cardiogenic shock. Key secondary outcomes will include all- cause mortality or admission with heart failure at 12 months, all-cause mortality at 12 months and admission to hospital with heart failure at 12 months.

A cornerstone of this research programme will be to determine the cost-efficacy of ECMO in this setting. Cost benefit will be measured both immediately and in the longer term testing for example any impact of need for heart failure therapies. This will be undertaken with evaluations of the cost-effectiveness of the device and evaluation of quality of life using the EuroQuol-5D-5L and the Minnesota Living with Heart Failure Questionnaire.

The EUROSHOCK trial will also include the following sub-studies:

1. Cardiovascular MRI: Cardio-Renal Imaging Sub-study using novel shortened, non-breath-holding protocols.
2. Platelet Function Sub-study designed to access the impact of novel ECMO coatings on platelet activation.

The programme will be developed and run through a carefully thought through management structure comprising 8 separate but interlinked work programmes (each targeted at one aspect of the project and headed by an experienced clinical trialist or trial manager) and involve the dissemination of results through a designated dissemination work package. Attention to translating the results to subsequent on-the-ground patient care will be an important aim for the management and dissemination team, and will involve patient support groups, professional societies and information delivered directly to the medical and non- medical staff caring for CGS patients.

Eligibility criteria: Inclusion Criteria:

1. Willing to provide informed consent/assent.
2. Presentation CGS within 24 hours of onset of Acute Coronary Syndrome (ACS) symptoms.
3. CGS can only be secondary to ACS (Type 1 MI STEMI or N-STEMI) or secondary to ACS following previous recent PCI (acute/sub-acute stent thrombosis ARC)
4. PCI has been attempted.
5. Persistence of CGS 30 minutes after successful or unsuccessful revascularisation of culprit coronary artery to allow for echocardiography and clinical assessment.

   CGS will be defined by the following 2 criteria:

   • Systolic blood pressure \<90 mmHg for at least 30 minutes, or 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.
6. Provision of informed assent followed by patient consent; \[or relative or physician consent if the patient is unable to consent\].

Exclusion Criteria:

1. Unwilling to provide informed assent/consent.
2. Echocardiographic evidence) of mechanical cause for CGS: eg ventricular septal defect, LV-free wall rupture, ischaemic mitral regurgitation (recorded within 30 mins of end of PCI procedure).
3. Age \<18 and\>90 years.
4. Deemed appropriately frail (≥ 5 Canadian frailty score)
5. Shock from another cause (sepsis, haemorrhagic/hypovolaemic shock, anaphylaxis, myocarditis etc.).
6. Significant systemic illness
7. Known dementia of any severity.
8. Comorbidity with life expectancy \<12 months.
9. Severe peripheral vascular disease (precluding access making ECMO contra- indicated).
10. Severe allergy or intolerance to pharmacological or antithrombotic anti-platelet agents.
11. Out-of-hospital cardiac arrest (OHCA) under any of the following circumstances:-

    * without return of spontaneous circulation (ongoing resuscitation effort).
    * without pH or \>7 without bystander CPR within 10 minutes of collapse.
12. Involved in another randomised research trial within the last 12 months.
13. Arterial lactate level of \<2.0 mmol per litre.

Primary outcomes:
measure: All-cause mortality at 30 days
timeFrame: at 30 days
Secondary outcomes:
measure: All-cause mortality or admission for heart failure at 12 months
timeFrame: at 12 months
measure: All-cause mortality at 12 months
timeFrame: at 12 months
measure: Admission for heart failure at 12 months
timeFrame: at 12 months
Other outcomes:
measure: All-cause mortality
timeFrame: From date of index hospital admission to date of discharge from hospital, assessed up to 12 months.
measure: Cardiovascular mortality
timeFrame: From date of index hospital admission to date of discharge from hospital, assessed up to 12 months.
measure: Stroke.
timeFrame: From date of index hospital admission to date of discharge from hospital, assessed up to 12 months
measure: Recurrent Myocardial Infarction
timeFrame: From date of index hospital admission to date of discharge from hospital, assessed up to 12 months.
measure: Bleeding (BARC Type 3-5)
timeFrame: From date of index hospital admission to date of discharge from hospital, assessed up to 12 months.
measure: Escalation to other (non-ECMO) support device for refractory shock
timeFrame: From date of index hospital admission to date of discharge from hospital, assessed up to 12 months.
measure: Any vascular complications
timeFrame: From date of index hospital admission to date of discharge from hospital, assessed up to 12 months.
measure: Acute Kidney Injury according to the modified RIFLE classification
timeFrame: From date of index hospital admission to date of discharge from hospital, assessed up to 12 months.
measure: MACCE (Major Adverse Cardiovascular and Cerebrovascular Events)
timeFrame: at 12 months
measure: Cardiovascular mortality
timeFrame: at 12 months
measure: Recurrent Myocardial Infarction
timeFrame: at 12 months
measure: Stroke
timeFrame: at 12 months
measure: Need for unplanned (Ischaemia-Driven) repeat revascularization (PCI and/or CABG) after index procedure [staged procedures excluded]
timeFrame: at 12 months
measure: Failure of discharge from primary admission as measured at 30 days
timeFrame: at 30 days
measure: Bleeding (BARC Type 3-5)
timeFrame: at 12 months
measure: Infarct size on Cardiac Magnetic Resonance Imaging
timeFrame: From date of index hospital admission to date of discharge from hospital, assessed up to 12 months.
measure: Cost effectiveness
timeFrame: at 12 months
measure: Quality of Life as assessed using the EuroQuol-5D-5L (measured at discharge, 6 and 12 months)
timeFrame: on day of discharge from hospital following index admission, at 6 months and at 12 months
measure: Quality of Life assessed using the Minnesota Living with heart failure questionnaire (measured at discharge, 6 and12 months)
timeFrame: on day of discharge from hospital following index admission, at 6 months and at 12 months
Locations:
city: Wien
country: Austria
facility: Medical University of Vienna
state: Vienna
city: Aalst
country: Belgium
facility: Algemeen Stedelijk Ziekenhuis Aalst
city: Aalst
country: Belgium
facility: Onze Lieve Vrouw Hospital Aalst
city: Antwerpen
country: Belgium
facility: University Hospital Antwerpen
city: Antwerpen
country: Belgium
facility: ZNA Middelheim
city: Bonheiden
country: Belgium
facility: Imelda Hospital Bonheiden
city: Deurne
country: Belgium
facility: AZ Monica
city: Gent
country: Belgium
facility: AZ Gent
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis Hasselt
city: Leuven
country: Belgium
facility: Katholieke Universiteit Leuven
city: Turnhout
country: Belgium
facility: AZ Turnhout
city: Bad Krozingen
country: Germany
facility: Universitäts-Herzzentrum Freiburg-Bad Krozingen
city: Bad Segeberg
country: Germany
facility: Segeberger Kliniken GmbH
city: Konstanz
country: Germany
facility: Herz-Zentrum Bodensee
city: Munich
country: Germany
facility: Klinikum Rechts Der Isar
city: München
country: Germany
facility: Klinikum Campus Innenstadt
city: München
country: Germany
facility: Deutsches Herzzentrum München
city: München
country: Germany
facility: Barmherzige Brüder gemeinnützige Krankenhaus GmbH
city: München
country: Germany
facility: Klinik Augustinum
city: München
country: Germany
facility: Ludwig-Maximilians-Universität München
city: Tübingen
country: Germany
facility: Uniklinikum Tübingen
city: Bergamo
country: Italy
facility: Azienda Ospedalierea Papa Giovanni XXIII
city: Bologna
country: Italy
facility: University Hospital of Bologna Policlinico S. Orsola - Malpighi
city: Firenze
country: Italy
facility: Azienda Universitaria Ospedaliera Careggi, Firenze
city: Padova
country: Italy
facility: Università degli Studi di Padova
city: Torino
country: Italy
facility: Ospedale San Giovanni Bosco di Torino
city: Riga
country: Latvia
facility: Paula Stradina Liniska Universitates Slimnica AS
city: Bodø
country: Norway
facility: The Nordland Hospital
city: Hammerfest
country: Norway
facility: The Finnmark Hospital
city: Mo I Rana
country: Norway
facility: The Helgeland Hospital
city: Tromsø
country: Norway
facility: Universitetet i Tromsoe
city: Badalona
country: Spain
facility: Hospital Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Consorci Institut D'Investicacions Biomediques August Pi i Sunyer / Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de Sant Pau
city: Barcelona
country: Spain
facility: Hospital de Bellvitge
city: Leicester
country: United Kingdom
facility: University Hospital Leicester
state: East Midlands
city: Airdrie
country: United Kingdom
facility: Hairmyres Hospital
state: Lanarkshire
city: Leicester
country: United Kingdom
facility: University of Leicester
state: Leicestershire
city: Newcastle
country: United Kingdom
facility: Newcastle Freeman Hospital
state: Newcastle Upon Tyne
city: Glasgow
country: United Kingdom
facility: University of Glasgow
state: Scotland
city: Cambridge
country: United Kingdom
facility: Papworth Hospital
city: Glasgow
country: United Kingdom
facility: Golden Jubilee National Hospital
city: London
country: United Kingdom
facility: St Barts and the London Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: Harefield and Brompton London
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust
Study officials:
affiliation: University of Leicester
name: Anthony H Gershlick
role: PRINCIPAL_INVESTIGATOR
References: