ANCHOR: Assessment of ECMO in Acute Myocardial Infarction Cardiogenic Shock

• Sponsor: Assistance Publique - Hôpitaux de Paris (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04184635
• Collaborator: (none)
• Enrollment: 400
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 36.6
• Patients Per Site Per Month: 10.9

Study Details

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	N/A

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

• 1. 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
• 1. Refractory cardiac arrest

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

Study Design

• Study Type: Interventional
• Anticipated 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.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: Oct 14, 2021
• Anticipated Primary Completion Date: Dec 2, 2023
• Anticipated Study Completion Date: Nov 2, 2024

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 [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 [At day 30]

   All-cause mortality at day 30

2. Major Adverse Cardiovascular Events [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 [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 [At day 30]

   Recurrent myocardial infarction

5. Need for repeat revascularization with PCI and/or CABG [At day 30]

   Need for repeat revascularization (PCI and/or CABG)

6. Need for renal replacement therapy [At day 30]

   Need for renal replacement therapy

7. Re-hospitalization for heart failure [At day 30]

   re-hospitalization for heart failure

8. Escalation to LVAD or total artificial heart [At day 30]

   Escalation to permanent left ventricular assist device or total artificial heart

9. Cardiac transplantation [At day 30]

   Cardiac transplantation

10. Major bleeding [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 [At day 30]

    Number of packed red blood cells transfused

12. Serum lactate [At day 30]

    Time to serum lactate normalization

13. Number of days alive without organ failure at day 30 [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 [At day 30]

    Durations of ICU stay and of hospitalization

15. LV function [At day 30]

    LV function assessed with Doppler echocardiography or magnetic resonance imaging

16. NYHA/INTERMACS status [At day 30]

    NYHA/INTERMACS status

17. ECMO-related complications [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 [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 [At one year]

    All-cause mortality

20. Major Adverse Cardiovascular at one year [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 [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 [At one year]

    Recurrent myocardial infarction between randomization and one year

23. PCI and/or CABG at one year [At one year]

    Repeat revascularization (PCI and/or CABG) between randomization and one year

24. Renal replacement therapy at one year [At one year]

    Need for renal replacement therapy between randomization and one year

25. Re-hospitalization for heart failure [At one year]

    Re-hospitalization for heart failure between randomization and one year

26. LVAD at one year [At one year]

    Escalation to permanent left ventricular assist device (LVAD) or total artificial heart

27. Cardiac transplant at one year [At one year]

    Cardiac transplantation

28. Major bleeding at one year [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 [At one year]

    NYHA/INTERMACS status

30. Returned to work at one year [At one year]

    Rate of patients who returned to work if previously active

31. LV ejection fraction at one year [At one year]

    Latest LV ejection fraction

32. Short Form 36 (SF-36) questionnaire at one year [At one year]

    Quality of life assessed using the Short Form 36 (SF-36) Health Survey questionnaire

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

• Authors/Task Force members, Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Jüni 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.
• Muller G, Flecher E, Lebreton G, Luyt CE, Trouillet JL, Bréchot 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.
• 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.
• 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.
• 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.

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT04184635
• Other Study ID Numbers: P140936; N°ID-RCB : 2019-A00275-52
• First Posted: Dec 3, 2019
• Last Update Posted: Aug 23, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• 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

Study Results

No Results Posted as of Aug 23, 2022