Clinical trial NCT04184635: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Myocardial Infarction
Cardiogenic Shock
Keywords: cardiogenic shock
VA-ECMO
STEMI
NSTEMI
Intraortic balloon pump
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2019-12-03
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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.

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

Primary outcomes:
measure: Treatment failure at Day 30
timeFrame: At day 30
Secondary outcomes:
measure: Mortality at Day 30
timeFrame: At day 30
measure: Major Adverse Cardiovascular Events
timeFrame: At day 30
measure: Stroke
timeFrame: At day 30
measure: Recurrent myocardial infarction
timeFrame: At day 30
measure: Need for repeat revascularization with PCI and/or CABG
timeFrame: At day 30
measure: Need for renal replacement therapy
timeFrame: At day 30
measure: Re-hospitalization for heart failure
timeFrame: At day 30
measure: Escalation to LVAD or total artificial heart
timeFrame: At day 30
measure: Cardiac transplantation
timeFrame: At day 30
measure: Major bleeding
timeFrame: At day 30
measure: Red blood cells transfused
timeFrame: At day 30
measure: Serum lactate
timeFrame: At day 30
measure: Number of days alive without organ failure at day 30
timeFrame: At day 30
measure: Durations of ICU stay and hospitalization
timeFrame: At day 30
measure: LV function
timeFrame: At day 30
measure: NYHA/INTERMACS status
timeFrame: At day 30
measure: ECMO-related complications
timeFrame: At day 30
measure: Treatment failure at one year
timeFrame: At one year
measure: Mortality at one year
timeFrame: At one year
measure: Major Adverse Cardiovascular at one year
timeFrame: At one year
measure: Stroke at one year
timeFrame: At one year
measure: Recurrent myocardial infarction at one year
timeFrame: At one year
measure: PCI and/or CABG at one year
timeFrame: At one year
measure: Renal replacement therapy at one year
timeFrame: At one year
measure: Re-hospitalization for heart failure
timeFrame: At one year
measure: LVAD at one year
timeFrame: At one year
measure: Cardiac transplant at one year
timeFrame: At one year
measure: Major bleeding at one year
timeFrame: At one year
measure: NYHA/INTERMACS status at one year
timeFrame: At one year
measure: Returned to work at one year
timeFrame: At one year
measure: LV ejection fraction at one year
timeFrame: At one year
measure: Short Form 36 (SF-36) questionnaire at one year
timeFrame: At one year
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Pitié Salpétrière
Study officials:
affiliation: Centre Hospitalier Universitaire Pitié-Salpêtrière Paris
name: Alain COMBES, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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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.
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