Assessment of ECMO in Acute Myocardial Infarction Cardiogenic Shock (ANCHOR)

• ClinicalTrials.gov Identifier: NCT04184635
• Recruitment Status: Suspended
• First Posted: December 3, 2019
• Last Update Posted: April 30, 2024
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Acute Myocardial Infarction; Cardiogenic Shock	Device: VA-ECMO	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 400 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A multicenter, prospective, randomized, comparative open trial will be conducted on two parallel groups of patients with AMI complicated by cardiogenic shock.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Assessment of ECMO in Acute Myocardial Infarction With Non-reversible Cardiogenic Shock to Halt Organ Failure and Reduce Mortality (ANCHOR)
• Actual Study Start Date: October 14, 2021
• Estimated Primary Completion Date: October 14, 2024
• Estimated Study Completion Date: October 14, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Experimental ECMO + IABP Arm; VA-ECMO will be instituted percutaneously under echo guidance via the femoral route as soon as possible. An IABP will be systematically inserted in the contralateral femoral artery (unless technically not possible).	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).
No Intervention: Control Conventional Treatment Arm; Standard management of cardiogenic shock due to myocardial infarction according to the current ESC guidelines. It is not recommended to use IABP support and no other TCS device (e.g., ECMO, Impella, Thoratec PHP, TandemHeart) will be permitted in the control group.

Outcome Measures

Primary Outcome Measures :

1. Treatment failure at Day 30 [ Time Frame: At day 30 ]
   Death in the ECMO group and death OR rescue ECMO in the control group

Secondary Outcome Measures :

1. Mortality at Day 30 [ Time Frame: At day 30 ]
   All-cause mortality at day 30
2. Major Adverse Cardiovascular Events [ Time Frame: At day 30 ]
   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.
3. Stroke [ Time Frame: At day 30 ]
   Any new neurological symptoms in association with signs of ischemia or hemorrhage in a cranial CT or MRI
4. Recurrent myocardial infarction [ Time Frame: At day 30 ]
   Recurrent myocardial infarction
5. Need for repeat revascularization with PCI and/or CABG [ Time Frame: At day 30 ]
   Need for repeat revascularization (PCI and/or CABG)
6. Need for renal replacement therapy [ Time Frame: At day 30 ]
   Need for renal replacement therapy
7. Re-hospitalization for heart failure [ Time Frame: At day 30 ]
   re-hospitalization for heart failure
8. Escalation to LVAD or total artificial heart [ Time Frame: At day 30 ]
   Escalation to permanent left ventricular assist device or total artificial heart
9. Cardiac transplantation [ Time Frame: At day 30 ]
   Cardiac transplantation
10. Major bleeding [ Time Frame: At day 30 ]
    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)
11. Red blood cells transfused [ Time Frame: At day 30 ]
    Number of packed red blood cells transfused
12. Serum lactate [ Time Frame: At day 30 ]
    Time to serum lactate normalization
13. Number of days alive without organ failure at day 30 [ Time Frame: At day 30 ]
    Number of days alive without organ failure(s) defined with the SOFA score, catecholamine support, mechanical ventilation and renal replacement therapy
14. Durations of ICU stay and hospitalization [ Time Frame: At day 30 ]
    Durations of ICU stay and of hospitalization
15. LV function [ Time Frame: At day 30 ]
    LV function assessed with Doppler echocardiography or magnetic resonance imaging
16. NYHA/INTERMACS status [ Time Frame: At day 30 ]
    NYHA/INTERMACS status
17. ECMO-related complications [ Time Frame: At day 30 ]
    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).
18. Treatment failure at one year [ Time Frame: 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.
19. Mortality at one year [ Time Frame: At one year ]
    All-cause mortality
20. Major Adverse Cardiovascular at one year [ Time Frame: 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.
21. Stroke at one year [ Time Frame: At one year ]
    Stroke (any new neurological symptoms in association with signs of ischemia or hemorrhage in a cranial CT or MRI),
22. Recurrent myocardial infarction at one year [ Time Frame: At one year ]
    Recurrent myocardial infarction between randomization and one year
23. PCI and/or CABG at one year [ Time Frame: At one year ]
    Repeat revascularization (PCI and/or CABG) between randomization and one year
24. Renal replacement therapy at one year [ Time Frame: At one year ]
    Need for renal replacement therapy between randomization and one year
25. Re-hospitalization for heart failure [ Time Frame: At one year ]
    Re-hospitalization for heart failure between randomization and one year
26. LVAD at one year [ Time Frame: At one year ]
    Escalation to permanent left ventricular assist device (LVAD) or total artificial heart
27. Cardiac transplant at one year [ Time Frame: At one year ]
    Cardiac transplantation
28. Major bleeding at one year [ Time Frame: 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)
29. NYHA/INTERMACS status at one year [ Time Frame: At one year ]
    NYHA/INTERMACS status
30. Returned to work at one year [ Time Frame: At one year ]
    Rate of patients who returned to work if previously active
31. LV ejection fraction at one year [ Time Frame: At one year ]
    Latest LV ejection fraction
32. Short Form 36 (SF-36) questionnaire at one year [ Time Frame: At one year ]
    Quality of life assessed using the Short Form 36 (SF-36) Health Survey questionnaire

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

France

Hôpital Pitié Salpétrière

Paris, France, 75013

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

• Principal Investigator: Alain COMBES, MD, PhD; Centre Hospitalier Universitaire Pitié-Salpêtrière Paris

More Information

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 Myocardial Infarction and Cardiogenic Shock. N Engl J Med. 2017 Dec 21;377(25):2419-2432. doi: 10.1056/NEJMoa1710261. Epub 2017 Oct 30.

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.

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.

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.

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.

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT04184635
• Other Study ID Numbers: P140936; N°ID-RCB : 2019-A00275-52 ( Other Identifier: ANSM )
• First Posted: December 3, 2019
• Last Update Posted: April 30, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:

cardiogenic shock; VA-ECMO; STEMI; NSTEMI; Intraortic balloon pump

Additional relevant MeSH terms:

Myocardial Infarction; Shock, Cardiogenic; Infarction; Shock; Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases