Periodic Reporting for period 4 - EURO SHOCK (Testing the value of a novel strategic approach and its cost efficacy to improve the poor outcomes in Cardiogenic Shock)
Periodo di rendicontazione: 2022-07-01 al 2022-12-31
Cardio-vascular disease (CVD) is a major cause of death, with a case fatality rate of 160/100 000 caused by ischaemic heart disease alone in an EU census in 2016, resulting in about 4 million death per year. CVD also carries a significant burden of morbidity and adverse social impact due to loss of earnings due to premature deaths and impaired quality of life in those living with CVD. This makes CVD one of the biggest threats to public health in Europe. One condition with major mortality and morbidity is Cardiogenic Shock (CGS) which can occur after a large heart attack that extensively damages the heart muscle function. Patients with cardiogenic shock have a 50% chance of dying within the first 30 days. This incidence of death has not changed in 20 years despite various small studies of therapeutic strategies designed to attenuate mortality. It is estimated that more than 50,000 people are diagnosed with CGS each year in the EU. In addition to the high mortality there is a major impact on morbidity at a cost to the European economy of about €210 billion a year. Despite high mortality rates and immense health care expenses, little quality robust research has been conducted to determine if there are potentially useful treatments or procedures that could alter the poor prognosis as current interventions show little impact on outcomes.
EURO SHOCK was conceived as the first large-scale clinical study testing extracorporeal membrane oxygenation (ECMO), a novel intervention strategy aimed at reducing the high mortality associated with CGS and alleviating the associated burden of chronic heart failure. The appropriately powered randomised clinical trial at the centre of the project was designed to assess whether the very early use of ECMO in the acute phase of CGS, supplementing primary percutaneous coronary intervention (PCI) and standard pharmaco-therapies, can stop the cycle of decline in patients and reduce cardiac mortality compared to the current standard of therapy alone. The project also planned to test if a system of urgent transfer of unwell patients to specialist ECMO centres is practical, and whether there are markers that predict worse outcomes when selecting patients for best-expedited treatments. The use of Cardiac Magnetic Imaging is an important mechanistic sub-study. EURO SHOCK further aimed to compare the cost-effectiveness of up-front ECMO to the cost of current standard care- such a cost-efficacy analysis will be central to any assessment of any benefit versus the price of any benefit (if) seen.
EURO SHOCK was conceived as the first large-scale clinical study testing extracorporeal membrane oxygenation (ECMO), a novel intervention strategy aimed at reducing the high mortality associated with CGS and alleviating the associated burden of chronic heart failure. The appropriately powered randomised clinical trial at the centre of the project was designed to assess whether the very early use of ECMO in the acute phase of CGS, supplementing primary percutaneous coronary intervention (PCI) and standard pharmaco-therapies, can stop the cycle of decline in patients and reduce cardiac mortality compared to the current standard of therapy alone. The project also planned to test if a system of urgent transfer of unwell patients to specialist ECMO centres is practical, and whether there are markers that predict worse outcomes when selecting patients for best-expedited treatments. The use of Cardiac Magnetic Imaging is an important mechanistic sub-study. EURO SHOCK further aimed to compare the cost-effectiveness of up-front ECMO to the cost of current standard care- such a cost-efficacy analysis will be central to any assessment of any benefit versus the price of any benefit (if) seen.
During the project, the Consortium focused on advancing the clinical trial at the centre of the project. The COVID-19 pandemic impacted EURO SHOCK in particular as the primary therapeutic intervention (ECMO) was extensively repurposed for the treatment of advanced COVID pneumonitis, and many of the health care professionals supporting EURO SHOCK were prioritised to the care of COVID patients. Professor Tony Gershlick, scientific lead for EURO SHOCK, also sadly passed away from COVID in November 2020. Following this, Professors Marcus Flather and Manel Sabate took over consortium leadership responsibilities with Dr Dave Adlam as sientific lead. Unfortunately, the clinical trial was unable to achieve its recruitment target and this was discussed with the Consortium, Trials Steering Committee and European Commission. A decision to suspend the trial was taken on 26th January 2022. Following this, close-down activities were commenced in February 2022.
At the time of suspension, there were 19 active recruiting sites in 8 countries. In total 35 participants were recruited and data were collected using an electronic CRF. The governance infrastructure for the programme was in place, including the Trial Steering Committee, the Independent Data Safety Monitoring Committee and Clinical Events Committee. Robust monitoring of patient data was supported by the experienced Cardiovascular European Research Centre (CERC).
To raise awareness for EURO SHOCK, a project website (www.euroshock-study.eu) tailored to different audiences was created. Outreach and dissemination activities were supported by materials, such as a roll-up and a project factsheet. Work on a pilot cardiac MRI study in CGS and novel approaches to remote patient monitoring is ongoing.
The number of patients recruited to the trial means that no definite conclusions could be drawn from the data available regarding the efficacy of VA-ECMO in cardiogenic shock. However, the data suggest a trend to a benefit with VA-ECMO with a numerically lower rate of 30-day and 1-year mortality with VA-ECMO compared to standard therapy alone. The 30-day all-cause mortality was 43.8% in patients randomised to VA-ECMO and 61.1% in patients randomised to standard therapy (HR=0.56 95%CI=0.21-1.45 p=0.22). The 1-year all-cause mortality rate was 51.8% in the VA-ECMO group and 81.5% in the standard therapy group (HR=0.52 95% CI=0.21-1.26 P=0.14). There were also numerically lower rates of the composite endpoint of all-cause mortality and readmission with heart failure and 12-month rate for readmission with heart failure. Vascular and bleeding complications occurred more often in the patients randomised to VA-ECMO compared to standard therapy (vascular complications VA-ECMO= 21.4%, standard therapy = 0%; bleeding complications VA-ECMO=35.7%, standard therapy = 5.6%), reflective of the highly invasive nature of this mechanical circulatory support device.
The findings from the main trial were presented by Prof Manel Sabate at the EuroPCR 2023 conference as a “late breaking trial” on 19th May 2023. The results were also published simultaneously in the peer-reviewed journal “EuroIntervention” (Banning AS, Sabate M et al. EuroIntervention 2023. DOI: 10.4244/EIJ-D-23-00204). The presentation and publication of the results disseminates the findings from this trial to the wider interventional cardiology community as well as other healthcare specialists involved in the care of patients with cardiogenic shock such as intensivists and heart failure specialists.
At the time of suspension, there were 19 active recruiting sites in 8 countries. In total 35 participants were recruited and data were collected using an electronic CRF. The governance infrastructure for the programme was in place, including the Trial Steering Committee, the Independent Data Safety Monitoring Committee and Clinical Events Committee. Robust monitoring of patient data was supported by the experienced Cardiovascular European Research Centre (CERC).
To raise awareness for EURO SHOCK, a project website (www.euroshock-study.eu) tailored to different audiences was created. Outreach and dissemination activities were supported by materials, such as a roll-up and a project factsheet. Work on a pilot cardiac MRI study in CGS and novel approaches to remote patient monitoring is ongoing.
The number of patients recruited to the trial means that no definite conclusions could be drawn from the data available regarding the efficacy of VA-ECMO in cardiogenic shock. However, the data suggest a trend to a benefit with VA-ECMO with a numerically lower rate of 30-day and 1-year mortality with VA-ECMO compared to standard therapy alone. The 30-day all-cause mortality was 43.8% in patients randomised to VA-ECMO and 61.1% in patients randomised to standard therapy (HR=0.56 95%CI=0.21-1.45 p=0.22). The 1-year all-cause mortality rate was 51.8% in the VA-ECMO group and 81.5% in the standard therapy group (HR=0.52 95% CI=0.21-1.26 P=0.14). There were also numerically lower rates of the composite endpoint of all-cause mortality and readmission with heart failure and 12-month rate for readmission with heart failure. Vascular and bleeding complications occurred more often in the patients randomised to VA-ECMO compared to standard therapy (vascular complications VA-ECMO= 21.4%, standard therapy = 0%; bleeding complications VA-ECMO=35.7%, standard therapy = 5.6%), reflective of the highly invasive nature of this mechanical circulatory support device.
The findings from the main trial were presented by Prof Manel Sabate at the EuroPCR 2023 conference as a “late breaking trial” on 19th May 2023. The results were also published simultaneously in the peer-reviewed journal “EuroIntervention” (Banning AS, Sabate M et al. EuroIntervention 2023. DOI: 10.4244/EIJ-D-23-00204). The presentation and publication of the results disseminates the findings from this trial to the wider interventional cardiology community as well as other healthcare specialists involved in the care of patients with cardiogenic shock such as intensivists and heart failure specialists.
Cardiogenic shock results in poor quality of life with frequent hospital admissions, dependence on carers and potential loss of employment. The EURO SHOCK aimed to improve the mortality, and in those who survive, their health and quality of life for EU citizens and the global population affected by it. Due to the inability of the project to recruit the required numbers of patients, EURO SHOCK was not able to provide results that will change practice or improve outcomes. However, the randomised data for the use of VA-ECMO in cardiogenic shock generated from this project could contribute to future meta-analyses with other RCTs that are ongoing in this area which could ultimately inform whether VA-ECMO could be of benefit in patients with cardiogenic shock complicating acute myocardial infarction.
A Scientific Symposium on the management of CGS was held in Barcelona on 2nd December with input from other groups in the field, including the ECLS SHOCK and ANCHOR trials. A descriptive report on the main findings of the projects has been provided in the relevant deliverable. The project has established a European network of investigators managing complex myocardial infarction patients, which allows for future collaboration and potential for improvements in health care.
A Scientific Symposium on the management of CGS was held in Barcelona on 2nd December with input from other groups in the field, including the ECLS SHOCK and ANCHOR trials. A descriptive report on the main findings of the projects has been provided in the relevant deliverable. The project has established a European network of investigators managing complex myocardial infarction patients, which allows for future collaboration and potential for improvements in health care.