Assessment of ECMO in Acute Myocardial Infarction Cardiogenic Shock

Official title

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

Overview

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.

Detailed 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.

Interventions

• 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).

Primary outcome measures

• Treatment failure at Day 30 [Time frame: At day 30]

Secondary outcome measures (12)

• Mortality at Day 30 [Time frame: At day 30]
• Major Adverse Cardiovascular Events [Time frame: At day 30]
• Stroke [Time frame: At day 30]
• Recurrent myocardial infarction [Time frame: At day 30]
• Need for repeat revascularization with PCI and/or CABG [Time frame: At day 30]
• Need for renal replacement therapy [Time frame: At day 30]
• Re-hospitalization for heart failure [Time frame: At day 30]
• Escalation to LVAD or total artificial heart [Time frame: At day 30]
• Cardiac transplantation [Time frame: At day 30]
• Major bleeding [Time frame: At day 30]
• Red blood cells transfused [Time frame: At day 30]
• Serum lactate [Time frame: At day 30]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 1 center

• Hôpital Pitié Salpétrière — Paris

Publications

• 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 Myo PMID 29083953
• 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 PMID 25173339
• 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-Y PMID 30145971
• 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. PMID 29400656
• 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. PMID 26825953

Identifiers

NCT: NCT04184635 · P140936 · N°ID-RCB : 2019-A00275-52

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗