Testing the Value of Novel Strategy and Its Cost Efficacy in Order to Improve the Poor Outcomes in Cardiogenic Shock

NCT ID: NCT03813134

Last Updated: 2021-05-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

428 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-11

Study Completion Date

2024-02-01

Brief Summary

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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

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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.

Conditions

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Cardiogenic Shock

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective, open, multicentre, randomised strategy trial in Cardiogenic Shock (CGS)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Immediate PCI with medical therapy

Group 1 will receive immediate revascularisation with Percutaneous Coronary Intervention (PCI) to the culpirit lesion only) + standard care (pharmacological support titrated to attain SBP \>90mmHg).

No mechanical support device allowed.

Group Type ACTIVE_COMPARATOR

Percutaneous coronary intervention (PCI)

Intervention Type PROCEDURE

Primary PCI or early/immediate PCI for NSTEMI will be undertaken according to recommended Guideline standards of care. This will include appropriate pre-loading with dual anti-platelet therapy, a preferred radial approach, intra-procedural anti-coagulation (with measure of ACT if considered appropriate every 30 minutes) and the use of drug eluting stents. Treatment will be delivered essentially to the culprit vessel only. A successful procedure will be one considered to have achieved TIMI 2-3 flow and residual stenosis \< 50%. PCI failure will not be an exclusion itself from the trial.

Pharmacological Support

Intervention Type OTHER

Use of pharmacological agents (Norepinephrine, Dobutamine, Levosimendan) according to ESC Guidelines to maintain mean arterial pressure \>75 mmHg in accordance with recognised standards of care. Changes in pharmacotherapy will NOT be regarded as escalation therapy. However the number of and dose of inotropes will be documented in the CRF.

Immediate PCI with early VA-ECMO

Group 2 will receive immediate PCI plus standard pharmacological support with early peripheral veno-arterial ECMO.

Group Type EXPERIMENTAL

Percutaneous coronary intervention (PCI)

Intervention Type PROCEDURE

Primary PCI or early/immediate PCI for NSTEMI will be undertaken according to recommended Guideline standards of care. This will include appropriate pre-loading with dual anti-platelet therapy, a preferred radial approach, intra-procedural anti-coagulation (with measure of ACT if considered appropriate every 30 minutes) and the use of drug eluting stents. Treatment will be delivered essentially to the culprit vessel only. A successful procedure will be one considered to have achieved TIMI 2-3 flow and residual stenosis \< 50%. PCI failure will not be an exclusion itself from the trial.

Pharmacological Support

Intervention Type OTHER

Use of pharmacological agents (Norepinephrine, Dobutamine, Levosimendan) according to ESC Guidelines to maintain mean arterial pressure \>75 mmHg in accordance with recognised standards of care. Changes in pharmacotherapy will NOT be regarded as escalation therapy. However the number of and dose of inotropes will be documented in the CRF.

VA-ECMO

Intervention Type DEVICE

Following PCI of the culprit lesion, patients will have ECMO initiated as soon as echocardiography (to exclude mechanical causes) has been completed, once they have been assessed as having failed to improve (with the aim to start ECMO as early as possible from 30 mins after completed P-PCI procedure ad fully established within 6 hours after randomisation).

Peripheral Veno-arterial ECMO will be employed with a flow rate according to individual patient needs. Other methods of LV unloading, distal limb perfusion, maintenance of ejection/aortic valve opening and anti-coagulation will be instituted as per sites' usual care.

A minimum 24 hours be allocated to the randomised therapy in order that strategy failure is demonstrated but this will be at the physicians' discretion.

Interventions

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Percutaneous coronary intervention (PCI)

Primary PCI or early/immediate PCI for NSTEMI will be undertaken according to recommended Guideline standards of care. This will include appropriate pre-loading with dual anti-platelet therapy, a preferred radial approach, intra-procedural anti-coagulation (with measure of ACT if considered appropriate every 30 minutes) and the use of drug eluting stents. Treatment will be delivered essentially to the culprit vessel only. A successful procedure will be one considered to have achieved TIMI 2-3 flow and residual stenosis \< 50%. PCI failure will not be an exclusion itself from the trial.

Intervention Type PROCEDURE

Pharmacological Support

Use of pharmacological agents (Norepinephrine, Dobutamine, Levosimendan) according to ESC Guidelines to maintain mean arterial pressure \>75 mmHg in accordance with recognised standards of care. Changes in pharmacotherapy will NOT be regarded as escalation therapy. However the number of and dose of inotropes will be documented in the CRF.

Intervention Type OTHER

VA-ECMO

Following PCI of the culprit lesion, patients will have ECMO initiated as soon as echocardiography (to exclude mechanical causes) has been completed, once they have been assessed as having failed to improve (with the aim to start ECMO as early as possible from 30 mins after completed P-PCI procedure ad fully established within 6 hours after randomisation).

Peripheral Veno-arterial ECMO will be employed with a flow rate according to individual patient needs. Other methods of LV unloading, distal limb perfusion, maintenance of ejection/aortic valve opening and anti-coagulation will be instituted as per sites' usual care.

A minimum 24 hours be allocated to the randomised therapy in order that strategy failure is demonstrated but this will be at the physicians' discretion.

Intervention Type DEVICE

Other Intervention Names

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Veno-Arterial Extra Corporeal Membrane Oxygenation.

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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European Commission

OTHER

Sponsor Role collaborator

University of Glasgow

OTHER

Sponsor Role collaborator

KU Leuven

OTHER

Sponsor Role collaborator

University of East Anglia

OTHER

Sponsor Role collaborator

Deutsches Herzzentrum Muenchen

OTHER

Sponsor Role collaborator

A.O. Ospedale Papa Giovanni XXIII

OTHER

Sponsor Role collaborator

Chalice Medical Ltd

UNKNOWN

Sponsor Role collaborator

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role collaborator

University of Tromso

OTHER

Sponsor Role collaborator

Institut d'Investigacions Biomèdiques August Pi i Sunyer

OTHER

Sponsor Role collaborator

Paula Stradina Liniska Universitates

UNKNOWN

Sponsor Role collaborator

Accelopment AG

OTHER

Sponsor Role collaborator

Universiteit Antwerpen

OTHER

Sponsor Role collaborator

European Cardiovascular Research Center

NETWORK

Sponsor Role collaborator

University of Leicester

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Anthony H Gershlick

Role: PRINCIPAL_INVESTIGATOR

University of Leicester

Locations

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Medical University of Vienna

Vienna, Vienna, Austria

Site Status NOT_YET_RECRUITING

Algemeen Stedelijk Ziekenhuis Aalst

Aalst, , Belgium

Site Status NOT_YET_RECRUITING

Onze Lieve Vrouw Hospital Aalst

Aalst, , Belgium

Site Status NOT_YET_RECRUITING

University Hospital Antwerpen

Antwerp, , Belgium

Site Status NOT_YET_RECRUITING

ZNA Middelheim

Antwerp, , Belgium

Site Status NOT_YET_RECRUITING

Imelda Hospital Bonheiden

Bonheiden, , Belgium

Site Status NOT_YET_RECRUITING

AZ Monica

Deurne, , Belgium

Site Status NOT_YET_RECRUITING

AZ Gent

Ghent, , Belgium

Site Status NOT_YET_RECRUITING

Jessa Ziekenhuis Hasselt

Hasselt, , Belgium

Site Status NOT_YET_RECRUITING

Katholieke Universiteit Leuven

Leuven, , Belgium

Site Status RECRUITING

AZ Turnhout

Turnhout, , Belgium

Site Status NOT_YET_RECRUITING

Universitäts-Herzzentrum Freiburg-Bad Krozingen

Bad Krozingen, , Germany

Site Status NOT_YET_RECRUITING

Segeberger Kliniken GmbH

Bad Segeberg, , Germany

Site Status NOT_YET_RECRUITING

Herz-Zentrum Bodensee

Konstanz, , Germany

Site Status NOT_YET_RECRUITING

Klinikum Rechts Der Isar

Munich, , Germany

Site Status NOT_YET_RECRUITING

Klinikum Campus Innenstadt

München, , Germany

Site Status RECRUITING

Deutsches Herzzentrum München

München, , Germany

Site Status RECRUITING

Barmherzige Brüder gemeinnützige Krankenhaus GmbH

München, , Germany

Site Status NOT_YET_RECRUITING

Klinik Augustinum

München, , Germany

Site Status NOT_YET_RECRUITING

Ludwig-Maximilians-Universität München

München, , Germany

Site Status RECRUITING

Uniklinikum Tübingen

Tübingen, , Germany

Site Status NOT_YET_RECRUITING

Azienda Ospedalierea Papa Giovanni XXIII

Bergamo, , Italy

Site Status NOT_YET_RECRUITING

University Hospital of Bologna Policlinico S. Orsola - Malpighi

Bologna, , Italy

Site Status NOT_YET_RECRUITING

Azienda Universitaria Ospedaliera Careggi, Firenze

Florence, , Italy

Site Status NOT_YET_RECRUITING

Università degli Studi di Padova

Padua, , Italy

Site Status NOT_YET_RECRUITING

Ospedale San Giovanni Bosco di Torino

Torino, , Italy

Site Status NOT_YET_RECRUITING

Paula Stradina Liniska Universitates Slimnica AS

Riga, , Latvia

Site Status RECRUITING

The Nordland Hospital

Bodø, , Norway

Site Status NOT_YET_RECRUITING

The Finnmark Hospital

Hammerfest, , Norway

Site Status NOT_YET_RECRUITING

The Helgeland Hospital

Mo i Rana, , Norway

Site Status NOT_YET_RECRUITING

Universitetet i Tromsoe

Tromsø, , Norway

Site Status RECRUITING

Hospital Germans Trias I Pujol

Badalona, , Spain

Site Status RECRUITING

Hospital Vall d'Hebron

Barcelona, , Spain

Site Status RECRUITING

Consorci Institut D'Investicacions Biomediques August Pi i Sunyer / Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status RECRUITING

Hospital de Sant Pau

Barcelona, , Spain

Site Status NOT_YET_RECRUITING

Hospital de Bellvitge

Barcelona, , Spain

Site Status RECRUITING

University Hospital Leicester

Leicester, East Midlands, United Kingdom

Site Status NOT_YET_RECRUITING

Hairmyres Hospital

Airdrie, Lanarkshire, United Kingdom

Site Status NOT_YET_RECRUITING

University of Leicester

Leicester, Leicestershire, United Kingdom

Site Status RECRUITING

Newcastle Freeman Hospital

Newcastle, Newcastle Upon Tyne, United Kingdom

Site Status NOT_YET_RECRUITING

University of Glasgow

Glasgow, Scotland, United Kingdom

Site Status NOT_YET_RECRUITING

Papworth Hospital

Cambridge, , United Kingdom

Site Status NOT_YET_RECRUITING

Golden Jubilee National Hospital

Glasgow, , United Kingdom

Site Status NOT_YET_RECRUITING

St Barts and the London Hospital

London, , United Kingdom

Site Status NOT_YET_RECRUITING

Kings College Hospital

London, , United Kingdom

Site Status RECRUITING

Harefield and Brompton London

London, , United Kingdom

Site Status RECRUITING

Guys and St Thomas NHS Foundation Trust

London, , United Kingdom

Site Status NOT_YET_RECRUITING

Countries

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Austria Belgium Germany Italy Latvia Norway Spain United Kingdom

Central Contacts

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Anthony H Gershlick

Role: CONTACT

0116 256 3887

SAEEDA BASHIR

Role: CONTACT

07568591629

Facility Contacts

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Christian Hengstenberg

Role: primary

+4314040046140

Ian Buysschaert

Role: primary

+3253766730

Herbert De Raedt

Role: primary

+32537244 33

Steven Haine

Role: primary

+3238214281

Paul Vermeersch

Role: primary

+3232803211

William DeWilde

Role: primary

+3215505011

Guy Lenders

Role: primary

+3233205816

Michel De Pauw

Role: primary

+3293323460

Philippe Timmermans

Role: primary

+3211337023

Tom Adriaenssens

Role: primary

+3216344235

Mark Coosem

Role: primary

+3214406461

Franz-Josef Neumann

Role: primary

+498917973701

Gert Richardt

Role: primary

+49-4551-8024807

Klaus Tiroch

Role: primary

+497531897195

Tareq Ibrahim

Role: primary

+498941405994

Axel Bauer

Role: primary

+4989440052381

Adnan Kastrati

Role: primary

+498912184578

Roland Schmidt

Role: primary

+49-89-17973701

Christian Hagl

Role: primary

+4989440072950

Steffen Massberg

Role: primary

+4989440076074

Christian Schlensak

Role: primary

+4970712986638

Giulio Guagliumi

Role: primary

+390352673452

Francesco Saia

Role: primary

+39512144475

Carlo DiMario

Role: primary

+3955794111

Giuseppe Tarantini

Role: primary

+390498212586

Roberto Garbo

Role: primary

+39112402418

Andrejs Erglis

Role: primary

+37167452015

Knut Tore Lappegård

Role: primary

+4775534000

Bjørn Wembstad

Role: primary

+4778421000

Bjørn Haug

Role: primary

+4775065272

Truls Myrmel

Role: primary

+4777626612

Fina Mauri

Role: primary

+34934978989

Bruno Garcia del Blanco

Role: primary

+34932274835

Manel Sabate

Role: primary

+34606447666

Antonio Serra

Role: primary

+34935565775

Angel Cequier

Role: primary

+34932607686

Hakeem Yusuff

Role: primary

01162502315

Raymond Hamill

Role: primary

+441236712460

Anthony H Gershlick, MBBS, FRCP

Role: primary

0116 256 3887

Saeeda M Bashir

Role: backup

07568591629

Vijay Kunadian

Role: primary

+441912085797

Colin Berry

Role: primary

+441413301671

Alain Vuylsteke

Role: primary

+4401480364381

Catherine Sinclair

Role: primary

+44141 951 5440

Andreas Baumbach

Role: primary

+42078823909

Jonathan Hill

Role: primary

+442032995675

Richard Trimlett

Role: primary

+442073528121

Nicholas Barrett

Role: primary

Related Links

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Other Identifiers

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0658

Identifier Type: -

Identifier Source: org_study_id

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