Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03813134
Recruitment Status : Recruiting
First Posted : January 23, 2019
Last Update Posted : December 9, 2020
Sponsor:
Collaborators:
European Commission
University of Glasgow
KU Leuven
University of East Anglia
Deutsches Herzzentrum Muenchen
A.O. Ospedale Papa Giovanni XXIII
Chalice Medical Ltd
Ludwig-Maximilians - University of Munich
University of Tromso
Institut d'Investigacions Biomèdiques August Pi i Sunyer
Paula Stradina Liniska Universitates
Accelopment AG
Universiteit Antwerpen
Cardiovascular European Research Centre (CERC)
Information provided by (Responsible Party):
University of Leicester

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.


Condition or disease Intervention/treatment Phase
Cardiogenic Shock Procedure: Percutaneous coronary intervention (PCI) Other: Pharmacological Support Device: VA-ECMO Not Applicable

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 428 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Prospective, open, multicentre, randomised strategy trial in Cardiogenic Shock (CGS)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: EURO SHOCK Testing the Value of Novel Strategy and Its Cost Efficacy in Order to Improve the Poor Outcomes in Cardiogenic Shock
Actual Study Start Date : October 11, 2019
Estimated Primary Completion Date : March 3, 2023
Estimated Study Completion Date : February 1, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Shock

Arm Intervention/treatment
Active Comparator: 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.

Procedure: 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.

Other: 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.

Experimental: Immediate PCI with early VA-ECMO
Group 2 will receive immediate PCI plus standard pharmacological support with early peripheral veno-arterial ECMO.
Procedure: 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.

Other: 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.

Device: 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.

Other Name: Veno-Arterial Extra Corporeal Membrane Oxygenation.




Primary Outcome Measures :
  1. All-cause mortality at 30 days [ Time Frame: at 30 days ]
    Death from any cause


Secondary Outcome Measures :
  1. All-cause mortality or admission for heart failure at 12 months [ Time Frame: at 12 months ]
    Death from any cause, or admission to hospital for heart failure with typical symptoms (e.g. breathlessness, ankle swelling and fatigue) that may be accompanied by signs (e.g. elevated jugular venous pressure, pulmonary crackles and peripheral oedema) caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress.

  2. All-cause mortality at 12 months [ Time Frame: at 12 months ]
    Death from any cause

  3. Admission for heart failure at 12 months [ Time Frame: at 12 months ]
    Admission to hospital with clinical syndrome of heart failure, defined as per the ESC guidelines as typical symptoms (e.g. breathlessness, ankle swelling and fatigue) that may be accompanied by signs (e.g. elevated jugular venous pressure, pulmonary crackles and peripheral oedema) caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress.


Other Outcome Measures:
  1. All-cause mortality [ Time Frame: From date of index hospital admission to date of discharge from hospital, assessed up to 12 months. ]
    Death from any cause

  2. Cardiovascular mortality [ Time Frame: From date of index hospital admission to date of discharge from hospital, assessed up to 12 months. ]
    Death due to cardiovascular causes, including myocardial infarction, heart failure, cardiac arrhythmias, stroke, and sudden death suspected from cardiac aetiology.

  3. Stroke. [ Time Frame: From date of index hospital admission to date of discharge from hospital, assessed up to 12 months ]
    Acute neurological deficit lasting longer than 24 hours. The type of stroke will be categorised as: 1) Primary Haemorrhagic: either intracranial haemorrhage or subdural haematoma. 2)non-hemorrhagic cerebral infarction. 3)non-hemorrhagic cerebral infarction with haemorrhagic conversion. 4)Uncertain (any stroke without brain imaging [CT or MRI] or autopsy definition of type, or if tests are inconclusive).

  4. Recurrent Myocardial Infarction [ Time Frame: From date of index hospital admission to date of discharge from hospital, assessed up to 12 months. ]
    Defined as the presence of ischaemic symptoms of angina-type pain lasting longer than 20mins, its evidence of either ST-segment elevation/new Left Bundle Branch Block on ECG, or evidence of new Troponin elevation by greater than 20% of the last non-normalised reading, or angiographic evidence of re-occlusion of a previously opened artery or graft.

  5. Bleeding (BARC Type 3-5) [ Time Frame: From date of index hospital admission to date of discharge from hospital, assessed up to 12 months. ]
    Evidence of Bleeding as per the Bleeding Academic Research Consortium classification Type 3, Type 4 or Type 5.

  6. Escalation to other (non-ECMO) support device for refractory shock [ Time Frame: From date of index hospital admission to date of discharge from hospital, assessed up to 12 months. ]
    The use of either Impella or Tandem-Heart or LVAD support devices in patients with persistent cardiogenic shock despite revascularisation and uptitation of pharmacological support. Use of ECMO or non ECMO MSD in standard care group or to non ECMO device in intervention (ECMO) group will be regarded as a protocol violation and managed statistically as such in the final analysis.

  7. Any vascular complications [ Time Frame: From date of index hospital admission to date of discharge from hospital, assessed up to 12 months. ]
    Complications affecting the peripheral vasculature, defined by the Valve Academic Research Consortium (VARC)-2 classifications.

  8. Acute Kidney Injury according to the modified RIFLE classification [ Time Frame: From date of index hospital admission to date of discharge from hospital, assessed up to 12 months. ]
    Evidence of Acute Kidney Injury according to the RIFLE (Risk, Injury, Failure, Loss and End-stage kidney disease) classification stage 1 - 3.

  9. MACCE (Major Adverse Cardiovascular and Cerebrovascular Events) [ Time Frame: at 12 months ]
    combined endpoint of all-cause mortality, repeat MI, stroke and re-hospitalization for heart failure.

  10. Cardiovascular mortality [ Time Frame: at 12 months ]
    Death due to cardiovascular causes, including myocardial infarction, heart failure, cardiac arrhythmias, stroke, and sudden death from cardiac aetiology.

  11. Recurrent Myocardial Infarction [ Time Frame: at 12 months ]
    Defined as the presence of ischaemic symptoms of angina lasting longer than 20mins, its evidence of either ST-segment elevation/new Left Bundle Branch Block on ECG, or evidence of new Troponin elevation by greater than 20% of the last non-normalised reading, or angiographic evidence of re-occlusion of a previously opened artery or graft.

  12. Stroke [ Time Frame: at 12 months ]
    Acute neurological deficit lasting longer than 24 hours. The type of stroke will be categorised as: 1) Primary Haemorrhagic: either intracranial haemorrhage or subdural haematoma. 2)non-hemorrhagic cerebral infarction. 3)non-hemorrhagic cerebral infarction with haemorrhagic conversion. 4)Uncertain (any stroke without brain imaging [CT or MRI] or autopsy definition of type, or if tests are inconclusive).

  13. Need for unplanned (Ischaemia-Driven) repeat revascularization (PCI and/or CABG) after index procedure [staged procedures excluded] [ Time Frame: at 12 months ]
    REvascularisation procedure (either PCI or CABG) undertaken after index procedure in the context of ischaemic symptoms and evidence of myocardial ischaemia (ECG, stress perfusion scan, acute myocardial infarction) either to the culprit or non-culprit lesion. Planned elective staged procedures to the non-culprit lesion will not be included.

  14. Failure of discharge from primary admission as measured at 30 days [ Time Frame: at 30 days ]
    Patient remains an in-patient in hospital for on-going medical care following the index admission with acute coronary syndrome complicated by cardiogenic shock.

  15. Bleeding (BARC Type 3-5) [ Time Frame: at 12 months ]
    Evidence of Bleeding as per the Bleeding Academic Research Consortium classification Type 3, Type 4 or Type 5.

  16. Infarct size on Cardiac Magnetic Resonance Imaging [ Time Frame: From date of index hospital admission to date of discharge from hospital, assessed up to 12 months. ]
    The size of myocardial infarction, quantified as the percentage of myocaridum demonstrating late gadolinium enhancement consistent with acute myocardial injury.

  17. Cost effectiveness [ Time Frame: at 12 months ]
    The cost effectiveness of using early ECMO in patients with cardiogenic shock complicating acute myocardial infarction will be assessed using the Incremental Cost Effectiveness Ratio (ICER)

  18. Quality of Life as assessed using the EuroQuol-5D-5L (measured at discharge, 6 and 12 months) [ Time Frame: on day of discharge from hospital following index admission, at 6 months and at 12 months ]

    Assess the participants' general health status and self-reported quality of life using the EQ5D questionnaire. This is a 5 level EQ-5D standardised measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal.

    The EuroQuol (EQ)-5D-5L questionnaire assesses quality of life in study participants according to 5 domains (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each scored according to a scale of 1 (no problems) to 5 (indicating extreme problems) and generating a 5-digit code corresponding to quality of life. This will be used at discharge, 6 months and 12 months, and the within-subject change in EQ-5D-5L scores will be measured for this secondary outcome.


  19. Quality of Life assessed using the Minnesota Living with heart failure questionnaire (measured at discharge, 6 and12 months) [ Time Frame: on day of discharge from hospital following index admission, at 6 months and at 12 months ]
    This is a standardised measure of quality of life for patients living with heart failure. The questionnaire includes 21 physical, emotional and socio-economic ways in which heart failure can adversely affect the patients life, each domain is scored from 0 to 5 indicating how much heart failure has prevented the patient from living how he or she wanted to live over the preceding 4 weeks. This will be assessed for each patient at time of discharge, at 6-months and again at 12 months. The within-subject change in the MLFHQ questionnaire will be measured for each group.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03813134


Contacts
Layout table for location contacts
Contact: Anthony H Gershlick 0116 256 3887 ahg8@le.ac.uk
Contact: SAEEDA BASHIR 07568591629 saeeda.bashir@leicester.ac.uk

Locations
Show Show 47 study locations
Sponsors and Collaborators
University of Leicester
European Commission
University of Glasgow
KU Leuven
University of East Anglia
Deutsches Herzzentrum Muenchen
A.O. Ospedale Papa Giovanni XXIII
Chalice Medical Ltd
Ludwig-Maximilians - University of Munich
University of Tromso
Institut d'Investigacions Biomèdiques August Pi i Sunyer
Paula Stradina Liniska Universitates
Accelopment AG
Universiteit Antwerpen
Cardiovascular European Research Centre (CERC)
Investigators
Layout table for investigator information
Principal Investigator: Anthony H Gershlick University of Leicester
Additional Information:
Layout table for additonal information
Responsible Party: University of Leicester
ClinicalTrials.gov Identifier: NCT03813134    
Other Study ID Numbers: 0658
First Posted: January 23, 2019    Key Record Dates
Last Update Posted: December 9, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Leicester:
Cardiogenic Shock
Acute Myocardial Infarction
Acute Coronary Syndrome
Additional relevant MeSH terms:
Layout table for MeSH terms
Shock, Cardiogenic
Shock
Pathologic Processes
Myocardial Infarction
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases