Assessment of ECMO in Acute Myocardial Infarction Cardiogenic Shock

Acute Myocardial Infarction Clinical Trial

— ANCHOR  

Official title:

Assessment of ECMO in Acute Myocardial Infarction With Non-reversible Cardiogenic Shock to Halt Organ Failure and Reduce Mortality (ANCHOR)

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04184635
• Other study ID #: P140936
• Secondary ID: N°ID-RCB : 2019-
• Status: Suspended
• Phase: N/A
• Start date: October 14, 2021
• Est. completion date: October 14, 2025

Study information

• Verified date: April 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Data from case series and large retrospective trials suggest that the early treatment of cardiogenic shock AMI patients with the association of VA-ECMO and IABP may significantly decrease mortality, which is still unacceptably high nowadays (40-50% at 30 days).

An important benefit for the patients randomized to the ECMO arm is expected and the risk-to-benefit ratio is expected to be in favor of the experimental treatment arm.

Description:

Scientific background

• Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used more and more frequently in patients with acute myocardial infarction (AMI) and refractory cardiogenic shock despite the absence of high level scientific evidence to recommend the use of temporary circulatory support devices (TCS) in this setting.TCS support may also benefit to cardiogenic shock patients not initially refractory to conventional medical management since their mortality exceeds 40% and most of deaths are due to the development of refractory cardiogenic shock and multiple organ failure.

The ANCHOR trial is therefore designed to test the hypothesis that VA-ECMO support associated with IABP results in improved outcomes in comparison with optimal medical treatment alone in patients with AMI and cardiogenic shock. An ethical rescue option to VA-ECMO will however be provided to control patients with cardiogenic shock refractory to conventional medical treatment since recent data suggested survival up-to 50% with ECMO support in this setting.

Main objective - To determine if early VA-ECMO combined with IABP support and optimal medical treatment would improve the outcomes of patients with acute myocardial infarction complicated by cardiogenic shock as compared with optimal medical treatment alone.

Scope of the study

• Patients satisfying all of the Inclusion and Exclusion Criteria will be classified as 'Eligible'. Consent to research will be obtained from a close relative or surrogate for all eligible patients prior to randomization.

Should such a person be absent, eligible patients will be randomized according to the specifications of emergency consent and the patient will be asked to give his/her consent for the continuation of the trial when his/her condition will allow.

Randomization will be possible in centers with robust experience in the management of AMI and cardiogenic shock but no on-site ECMO capability providing that an ECMO retrieval team from the nearest ECMO center can establish ECMO no later than 2 hours after randomization.

Before randomization, physicians at the non-ECMO center will check that the ECMO team is immediately available and that an ICU/CCU bed is available at the ECMO center. Thereafter, if the patient is randomized to the ECMO arm, the mobile ECMO retrieval team will travel to the center, initiate VA-ECMO and will rapidly transfer the patient on VA-ECMO to the ECMO center.

Description of experimental ECMO + IABP Arm

• Protocolized conventional management of cardiogenic shock

• VA-ECMO will be started as soon as possible

• For patients randomized at non-ECMO centers, a mobile ECMO team will initiate ECMO at the non-ECMO center and transport the patient to the ECMO center immediately

• IABP inserted in the contralateral femoral artery (unless technically not possible)

• ECMO management according to protocol

• ECMO weaning according to protocol

Description of conventional treatment Arm

• Protocolized conventional management of cardiogenic shock

• IABP not recommended. No other TCS device (e.g., ECMO, Impella, Thoratec PHP, TandemHeart) permitted

• Rescue VA-ECMO only if one of 1 or 2 or 3 applies:

• 1. Refractory cardiogenic shock defined as

1. Cardiac index <1.2 l/min/m² or VTI <6 cm AND

2. Assessment and correction of hypovolemia AND

3. (dobutamine ≥15 microg/kg/min + norepinephrine ≥1.5 microg/kg/min) OR epinephrine ≥ 0.75 microg/kg/min

4. Serum lactate >5 mmol/L or serum lactate increased >50% in the last 6 hours

• 2. Uncontrolled lethal arrhythmia despite K >4.5 mmol/l AND Mg >1.0 mmol/l AND Intubation and mechanical ventilation with deep sedation AND IV Loading of amiodarone AND IV xylocaine

• 3. Refractory cardiac arrest

Mandatory validation of rescue VA-ECMO by an independent adjudicator.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 400
• Est. completion date: October 14, 2025
• Est. primary completion date: October 14, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Cardiogenic shock complicating acute myocardial infarction (STEMI or NSTEMI)

• Revascularization by PCI for acute myocardial infarction has been performed or is planned in the following 60 minutes

• Systolic blood pressure <90 mmHg for >30 min or catecholamine support required to maintain systolic blood pressure >90 mmHg

• Signs of pulmonary congestion

• Signs of impaired organ perfusion with at least one of the following:

Altered mental status OR cold, clammy skin and extremities OR oliguria with urine output <30 ml/h OR serum lactate >2.0 mmol/l

Exclusion Criteria:

• Age <18 years

• Pregnancy

• Onset of shock >24 Hours

• Shock of other cause (hypovolemic, anaphylactic or vagal shock)

• Shock due to massive pulmonary embolism

• Resuscitation >30 minutes

• No intrinsic heart activity

• Patient moribund on the day of randomization or SAPS II >90

• Surgical revascularization for AMI (CABG) planned or already performed prior to randomization

• Cerebral deficit with fixed dilated pupils or Irreversible neurological pathology

• Mechanical infarction complication (massive mitral regurgitation, pericardium drainage required, septal ventricular defect)

• Severe peripheral artery disease or previous aortic or ilio-femoral surgery precluding ECMO and IABP insertion

• Aortic regurgitation > II

• Other severe concomitant disease with limited life expectancy < 1 year

• Proven heparin-induced thrombocytopenia

• ECMO device not immediately available

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Cardiogenic Shock
• Infarction
• Myocardial Infarction
• Shock
• Shock, Cardiogenic

Intervention

Device:
• VA-ECMO
The ECMO device will be the CardioHelp (MAQUET, GETINGE, Orléans, France) using the veno-arterial setting and percutaneous femoro-femoral cannulation with MAQUET GETINGE HLS cannulae. Intraortic balloon pump will be MEGA 50 cc or 40cc, (MAQUET, GETINGE, Orléans, France).

Locations

Country	Name	City	State
France	Hôpital Pitié Salpétrière	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (5)

Authors/Task Force members; Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Juni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Sousa Uva M, Stefanini GG, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014 Oct 1;35(37):2541-619. doi: 10.1093/eurheartj/ehu278. Epub 2014 Aug 29. No abstract available. — View Citation

Muller G, Flecher E, Lebreton G, Luyt CE, Trouillet JL, Brechot N, Schmidt M, Mastroianni C, Chastre J, Leprince P, Anselmi A, Combes A. The ENCOURAGE mortality risk score and analysis of long-term outcomes after VA-ECMO for acute myocardial infarction with cardiogenic shock. Intensive Care Med. 2016 Mar;42(3):370-378. doi: 10.1007/s00134-016-4223-9. Epub 2016 Jan 29. — View Citation

Overtchouk P, Pascal J, Lebreton G, Hulot JS, Luyt CE, Combes A, Kerneis M, Silvain J, Barthelemy O, Leprince P, Brechot N, Montalescot G, Collet JP. Outcome after revascularisation of acute myocardial infarction with cardiogenic shock on extracorporeal life support. EuroIntervention. 2018 Apr 6;13(18):e2160-e2168. doi: 10.4244/EIJ-D-17-01014. — View Citation

Thiele H, Akin I, Sandri M, de Waha-Thiele S, Meyer-Saraei R, Fuernau G, Eitel I, Nordbeck P, Geisler T, Landmesser U, Skurk C, Fach A, Jobs A, Lapp H, Piek JJ, Noc M, Goslar T, Felix SB, Maier LS, Stepinska J, Oldroyd K, Serpytis P, Montalescot G, Barthelemy O, Huber K, Windecker S, Hunziker L, Savonitto S, Torremante P, Vrints C, Schneider S, Zeymer U, Desch S; CULPRIT-SHOCK Investigators. One-Year Outcomes after PCI Strategies in Cardiogenic Shock. N Engl J Med. 2018 Nov 1;379(18):1699-1710. doi: 10.1056/NEJMoa1808788. Epub 2018 Aug 25. — View Citation

Thiele H, Akin I, Sandri M, Fuernau G, de Waha S, Meyer-Saraei R, Nordbeck P, Geisler T, Landmesser U, Skurk C, Fach A, Lapp H, Piek JJ, Noc M, Goslar T, Felix SB, Maier LS, Stepinska J, Oldroyd K, Serpytis P, Montalescot G, Barthelemy O, Huber K, Windecker S, Savonitto S, Torremante P, Vrints C, Schneider S, Desch S, Zeymer U; CULPRIT-SHOCK Investigators. PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock. N Engl J Med. 2017 Dec 21;377(25):2419-2432. doi: 10.1056/NEJMoa1710261. Epub 2017 Oct 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment failure at Day 30	Death in the ECMO group and death OR rescue ECMO in the control group	At day 30
Secondary	Mortality at Day 30	All-cause mortality at day 30	At day 30
Secondary	Major Adverse Cardiovascular Events	Major Adverse Cardiovascular Events are defined as death, stroke (any new neurological symptoms in association with signs of ischemia or hemorrhage in a cranial CT or MRI), recurrent myocardial infarction, need for repeat revascularization (PCI and/or CABG), renal replacement therapy, re-hospitalization for heart failure, escalation to permanent left ventricular assist device (LVAD) or total artificial heart, cardiac transplant.	At day 30
Secondary	Stroke	Any new neurological symptoms in association with signs of ischemia or hemorrhage in a cranial CT or MRI	At day 30
Secondary	Recurrent myocardial infarction	Recurrent myocardial infarction	At day 30
Secondary	Need for repeat revascularization with PCI and/or CABG	Need for repeat revascularization (PCI and/or CABG)	At day 30
Secondary	Need for renal replacement therapy	Need for renal replacement therapy	At day 30
Secondary	Re-hospitalization for heart failure	re-hospitalization for heart failure	At day 30
Secondary	Escalation to LVAD or total artificial heart	Escalation to permanent left ventricular assist device or total artificial heart	At day 30
Secondary	Cardiac transplantation	Cardiac transplantation	At day 30
Secondary	Major bleeding	Major bleeding (TIMI definition): Any intracranial bleeding (excluding microhemorrhages <10 mm evident only on gradient-echo MRI) OR Clinically overt signs of hemorrhage associated with a drop in hemoglobin of =5 g/dL or a =15% absolute decrease in hematocrit OR Fatal bleeding (bleeding that directly results in death within 7 d)	At day 30
Secondary	Red blood cells transfused	Number of packed red blood cells transfused	At day 30
Secondary	Serum lactate	Time to serum lactate normalization	At day 30
Secondary	Number of days alive without organ failure at day 30	Number of days alive without organ failure(s) defined with the SOFA score, catecholamine support, mechanical ventilation and renal replacement therapy	At day 30
Secondary	Durations of ICU stay and hospitalization	Durations of ICU stay and of hospitalization	At day 30
Secondary	LV function	LV function assessed with Doppler echocardiography or magnetic resonance imaging	At day 30
Secondary	NYHA/INTERMACS status	NYHA/INTERMACS status	At day 30
Secondary	ECMO-related complications	ECMO-related complications (infection at VA-ECMO cannulation sites requiring antibiotics, hemorrhage, limb ischemia requiring surgery, cannula or circuit thrombosis, overt pulmonary edema, thrombocytopenia, gaseous emboli and hemolysis).	At day 30
Secondary	Treatment failure at one year	Treatment failure defined as death (all-cause) in the ECMO group and death (all-cause) OR rescue ECMO in the control group.	At one year
Secondary	Mortality at one year	All-cause mortality	At one year
Secondary	Major Adverse Cardiovascular at one year	MACE, Major Adverse Cardiovascular Events are defined as death, stroke (any new neurological symptoms in association with signs of ischemia or hemorrhage in a cranial CT or MRI), recurrent myocardial infarction, need for repeat revascularization (PCI and/or CABG), renal replacement therapy, re-hospitalization for heart failure, escalation to permanent left ventricular assist device (LVAD) or total artificial heart, cardiac transplant.	At one year
Secondary	Stroke at one year	Stroke (any new neurological symptoms in association with signs of ischemia or hemorrhage in a cranial CT or MRI),	At one year
Secondary	Recurrent myocardial infarction at one year	Recurrent myocardial infarction between randomization and one year	At one year
Secondary	PCI and/or CABG at one year	Repeat revascularization (PCI and/or CABG) between randomization and one year	At one year
Secondary	Renal replacement therapy at one year	Need for renal replacement therapy between randomization and one year	At one year
Secondary	Re-hospitalization for heart failure	Re-hospitalization for heart failure between randomization and one year	At one year
Secondary	LVAD at one year	Escalation to permanent left ventricular assist device (LVAD) or total artificial heart	At one year
Secondary	Cardiac transplant at one year	Cardiac transplantation	At one year
Secondary	Major bleeding at one year	Major bleeding (TIMI definition): Any intracranial bleeding (excluding microhemorrhages <10 mm evident only on gradient-echo MRI) OR Clinically overt signs of hemorrhage associated with a drop in hemoglobin of =5 g/dL or a =15% absolute decrease in hematocrit OR Fatal bleeding (bleeding that directly results in death within 7 d)	At one year
Secondary	NYHA/INTERMACS status at one year	NYHA/INTERMACS status	At one year
Secondary	Returned to work at one year	Rate of patients who returned to work if previously active	At one year
Secondary	LV ejection fraction at one year	Latest LV ejection fraction	At one year
Secondary	Short Form 36 (SF-36) questionnaire at one year	Quality of life assessed using the Short Form 36 (SF-36) Health Survey questionnaire	At one year