Clinical trial NCT06414187: Clinical Effects of Intra-aortic Balloon Support in Early Acute Coronary Syndrome and Non-Acute Coronary Syndrome Related Cardiogenic Shock
Official title: Clinical Effects of Intra-aortic Balloon Support in Early Acute Coronary Syndrome and Non-Acute Coronary Syndrome Related Cardiogenic Shock: a Multicenter Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Cardiogenic Shock
Keywords: Intra-aortic balloon pump
Mechanical circulatory support
Acute coronary syndrome
Ischemic cardiogenic shock
Non-ischemic cardiogenic shock
Cardiogenic shock
Decompensated heart failure
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: Arrow International LCC (Subsidiary of Teleflex Inc.)
First posted: 2024-05-16
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: Patients enrolled in this trial will be 1:1 randomized to IABP support or standard of care (i.e. inotropes and/or vasopressors, but no IABP insertion). Patients will be stratified for ACS/non-ischemic etiology and stage B/stage C cardiogenic shock following stratification according to center.
Primary purpose: TREATMENT

Brief summary: The goal of this randomized controlled trial is to appraise the impact of intra-aortic balloon pump (IABP) in the treatment of early stages of cardiogenic shock, irrespective of etiology. Findings of this randomized trial may enhance clinical decision making regarding the use of MCS in specific subsets of patients in early stages of cardiogenic shock.

The main questions it aims to answer are:

* What are the effects of IABP on a composite of clinical endpoints representing clinical deterioration at 30-days in patients presenting with SCAI stage B or C cardiogenic shock?
* What is the 1-year clinical outcome (including mortality and hospital admissions for cardiovascular causes) of patients treated with vs. without IABP for early cardiogenic shock?
* Is there a difference in efficacy of IABP within the treatment of early cardiogenic shock related to Acute Coronary Syndrome versus non-ischemic causes?
* Is there a difference in efficacy of IABP within the treatment of SCAI stage B versus stage C cardiogenic shock?

Participants will be 1:1 randomized to IABP support or standard of care (a treatment strategy including inotropes and/or vasopressors but no IABP insertion). Patients will be stratified for Acute Coronary Syndrome/non-ischemic etiology and stage B/stage C cardiogenic shock, following stratification to center. Researchers will compare the group who was randomized to IABP to the control group (i.e. standard of care) to see if there is a difference in the primary trial endpoint after 30-days, including 1) all-cause mortality, 2) escalation to invasive mechanical ventilation, 3) escalation of mechanical circulatory support strategy, 4) acute kidney injury and 5) stroke or transient ischemic attack.

Detailed description: Rationale: The scientific underpinning for the use of mechanical circulatory support (MCS) in early cardiogenic shock, especially for the intra-aortic balloon pump (IABP), is scarce and insufficiently clarified for different etiologies of cardiogenic shock. Previous randomized trials limited the inclusion criteria to patients with ischemic cardiogenic shock while observational research suggested favorable effects of timely adoption of IABP in patients with deteriorating myocardial function through ischemic or non-ischemic causes. Early stage of cardiogenic shock is defined by relative hypotension without hypoperfusion, or hypoperfusion still responsive to therapy (Society for Cardiovascular Angiography and Interventions, SCAI, stage B and C, respectively). A tightening of global guidelines with respect to the clinical adoption of IABP overshadowed the potential beneficial effects for specific patient categories within the total spectrum of cardiogenic shock. Patients currently presenting with early stages of cardiogenic shock caused by ischemic or non-ischemic etiology are hypothetically undertreated due to an assumed lack of clinical benefit of IABP in general. The aim of this randomized trial is to appraise the impact of IABP in the treatment of early stages of cardiogenic shock, irrespective of etiology. Findings of this randomized trial may enhance clinical decision making regarding the use of MCS in specific subsets of patients in early stages of cardiogenic shock.

Objective: The primary objective of this trial is to evaluate the 30-day clinical impact of IABP within the treatment of early (SCAI stage B or C) cardiogenic shock. Secondary objectives are

1) To evaluate the 1-year clinical outcome (including mortality and hospital admissions for cardiovascular causes) of patients treated with IABP for early cardiogenic shock; 2) To identify differences in efficacy of IABP in the treatment of early cardiogenic shock related to Acute Coronary Syndrome (ACS) versus non-ischemic causes; 3) To explore differences in efficacy of IABP in the treatment of stage B versus stage C cardiogenic shock.

Trial design: Open-label, multicenter, investigator-initiated, randomized controlled trial.

Trial population: The trial population consists of patients in early cardiogenic shock, defined as SCAI stage B or C, either related or unrelated to ACS.

Intervention: Patients enrolled in this trial will be 1:1 randomized to IABP support or standard of care (i.e. inotropes and/or vasopressors but no IABP insertion). Patients will be stratified for ACS/non-ischemic etiology and stage B/stage C cardiogenic shock following stratification according to center.

Eligibility criteria: Inclusion Criteria:

* At least 18 years of age;
* Stage B cardiogenic shock (presence of hypotension or tachycardia with signs of venous congestion, in absence of tissue hypoperfusion) OR
* Stage C cardiogenic shock (evidence of tissue hypoperfusion requiring any intervention beyond fluid management, still responsive to therapy) AND
* Must include at least one of the following: 1) lactate levels at least 2.0 mmol/L; 2) creatinine doubling OR \>50 percent decline in glomerular filtration rate compared to baseline; 3) laboratory markers indicating liver injury (e.g. high serum transaminase levels) or 4) elevated NT-pro BNP.

A patient is eligible for trial inclusion if, at the time of randomization, no more than 1 inotropic agent has been administered AND when the maximum dose of noradrenaline/norepinephrine has not exceeded 0.2 ug/kg/min in the context of mean arterial pressure \>65 mmHg.

Exclusion Criteria:

* The patient is in cardiogenic shock but does not fulfill the definition for stage B or C;
* Administration of at least 2 inotropic or vasopressive agents at study randomization;
* Administration of noradrenaline/norepinephrine exceeding 0.2 ug/kg/min at study randomization;
* Suspected or known mechanical complication contributing to cardiogenic shock, e.g. ventricular septal defect or papillary muscle rupture;
* Cardiogenic shock developing within 72 hours of a surgical procedure (i.e. low cardiac output with an inability to wean cardiopulmonary bypass);
* Inability to provide informed consent. Of not: patients admitted in cardiogenic shock who required cardiopulmonary resuscitation earlier, but are conscious at the time of hospital admission, are eligible for study participation;
* Known or suspected insufficiency of the aortic valve with at least moderate aortic regurgitation;
* Known or suspected peripheral arterial disease preventing safe insertion of IABP;
* Known or suspected thoracic or abdominal aortic disease (including aortic dissection or aortic aneurysm) precluding safe insertion of IABP;
* Suspicion of sepsis or septic shock (including septic cardiomyopathy);
* Pregnancy;
* Predicted life expectancy \<6 months because of concomitant disease;
* Concurrent participation in a clinical trial with competing endpoints.

Primary outcomes:
measure: Composite primary endpoint (percent)
timeFrame: 30-days post enrollment
Secondary outcomes:
measure: All-cause mortality (i.e. the individual determinants of the composite primary outcome) (percent)
timeFrame: 30-day follow-up
measure: Escalation to invasive mechanical ventilation (i.e. the individual determinants of the composite primary outcome
timeFrame: 30-day follow-up
measure: Escalation to mechanical circulatory support (i.e. the individual determinants of the composite primary outcome)
timeFrame: 30-day follow-up
measure: Acute kidney injury (i.e. the individual determinants of the primary outcome)
timeFrame: 30-day follow-up
measure: Stroke or transient ischemic attack (i.e. the individual determinants of the primary outcome)
timeFrame: 30-day follow-up
measure: Treatment escalation (percent)
timeFrame: 30-day follow-up
measure: Deterioration of SCAI stage B to C (percent)
timeFrame: 30-day follow-up
measure: Deterioration of cardiogenic shock (percent)
timeFrame: at 7 and 14 days after randomization
measure: Vascular complications defined according to VARC-3 guidelines (percent)
timeFrame: 30-day follow-up
measure: Major bleeding complications defined according to BARC guidelines (at least type 2) (percent)
timeFrame: 30-day follow-up
measure: De-novo Acute Coronary Syndrome (percent)
timeFrame: 30-day and 1-year follow-up
measure: Cardiopulmonary resuscitation or defibrillation (percent)
timeFrame: 30-day follow-up
measure: Development of SIRS, sepsis or severe sepsis (percent)
timeFrame: 96-hours after randomization
Other outcomes:
measure: Mortality (percent)
timeFrame: 30-day follow-up and 1-year follow-up
measure: Length of intensive care unit and hospital stay (in days)
timeFrame: 30-day follow-up
measure: Re-admission to the intensive care unit (percent)
timeFrame: 30-day follow-up
measure: Implantation of Left Ventricular Assist Device or heart transplant (percent)
timeFrame: 30-day follow-up
measure: Revascularization attempts (percent)
timeFrame: 30-day follow-up
measure: 1-Year composite endpoint (percent)
timeFrame: 1-year follow-up
measure: All-cause mortality (i.e. the individual determinants of the 1-year composite endpoint)
timeFrame: 1-year follow-up
measure: Hospital admission because of cardiovascular disease (i.e. the individual determinants of the 1-year composite endpoint)
timeFrame: 1-year follow-up
measure: Hospital re-admission (percent)
timeFrame: 1-year follow-up
measure: Visits to the emergency department (percent)
timeFrame: 1-year follow-up
measure: Unplanned revascularization (percent)
timeFrame: 1-year follow-up
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center
state: Zuid-Holland
Study officials:
affiliation: Erasmus Medical Center
name: Nicolas M Van Mieghem, Prof MD PhD
role: STUDY_CHAIR
References: