Clinical Effects of Intra-aortic Balloon Support in Early Acute Coronary Syndrome and Non-Acute Coronary Syndrome Related Cardiogenic Shock

Cardiogenic Shock Clinical Trial

— IABP ON-TIME  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06414187
• Other study ID #: IABP ON-TIME
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2024
• Est. completion date: June 1, 2027

Study information

• Verified date: May 2024
• Source: Erasmus Medical Center
• Contact: Antoon JM van den Enden, MD
• Phone: +31 10 7038896
• Email: a.vandenenden[@]erasmusmc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 400
• Est. completion date: June 1, 2027
• Est. primary completion date: June 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Cardiogenic Shock
• Shock
• Shock, Cardiogenic
• Syndrome

Intervention

Device:
• Intra-Aortic Balloon Pump
Patients who are randomized to the IABP-arm will be supported with IABP according to local, clinical guidelines (including algorithms for anticoagulation, verification of correct positioning and weaning strategies). The IABP console and disposables should be used according to the instructions for use, including the use of an appropriate-sized IABP balloon alligned with patient length and height.

Locations

Country	Name	City	State
Netherlands	Erasmus University Medical Center	Rotterdam	Zuid-Holland

Sponsors (2)

Lead Sponsor	Collaborator
Erasmus Medical Center	Arrow International LCC (Subsidiary of Teleflex Inc.)

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mortality (percent)	Including presumed cause of death	30-day follow-up and 1-year follow-up
Other	Length of intensive care unit and hospital stay (in days)	Stay after randomization	30-day follow-up
Other	Re-admission to the intensive care unit (percent)	After randomization	30-day follow-up
Other	Implantation of Left Ventricular Assist Device or heart transplant (percent)	After randomization	30-day follow-up
Other	Revascularization attempts (percent)	Including percutaneous coronary intervention or coronary artery bypass graft	30-day follow-up
Other	1-Year composite endpoint (percent)	Including 1) all-cause mortality and 2) hospital admission because of cardiovascular disease	1-year follow-up
Other	All-cause mortality (i.e. the individual determinants of the 1-year composite endpoint)	See 1-Year composite endpoint (percent), including 1) all-cause mortality and 2) hospital admission because of cardiovascular disease. Based on details stated in the patient's record.	1-year follow-up
Other	Hospital admission because of cardiovascular disease (i.e. the individual determinants of the 1-year composite endpoint)	See 1-Year composite endpoint (percent), including 1) all-cause mortality and 2) hospital admission because of cardiovascular disease. Based on details stated in the patient's record.	1-year follow-up
Other	Hospital re-admission (percent)	Including a description of the presumed cause of hospital (re-)admission	1-year follow-up
Other	Visits to the emergency department (percent)	Of note, visits necessitating treatment escalation for heart failure	1-year follow-up
Other	Unplanned revascularization (percent)	Including details concerning the revascularization attempt (i.e. percutaneous coronary intervention or coronary artery bypass graft)	1-year follow-up
Primary	Composite primary endpoint (percent)	The primary endpoint of the trial is the composite of the following outcomes: 1) all-cause mortality, 2) escalation to invasive mechanical ventilation, 3) escalation of mechanical circulatory support, 4) acute kidney injury and 5) stroke or transient ischemic attack.	30-days post enrollment
Secondary	All-cause mortality (i.e. the individual determinants of the composite primary outcome) (percent)	See primary outcome (%) (based on details stated in patient's records)	30-day follow-up
Secondary	Escalation to invasive mechanical ventilation (i.e. the individual determinants of the composite primary outcome	See primary outcome (%) (based on details stated in patient's records)	30-day follow-up
Secondary	Escalation to mechanical circulatory support (i.e. the individual determinants of the composite primary outcome)	See primary outcome (%) (based on details stated in patient's records)	30-day follow-up
Secondary	Acute kidney injury (i.e. the individual determinants of the primary outcome)	See primary outcome (%) (based on details stated in patient's records)	30-day follow-up
Secondary	Stroke or transient ischemic attack (i.e. the individual determinants of the primary outcome)	See primary outcome (%) (based on details stated in patient's records)	30-day follow-up
Secondary	Treatment escalation (percent)	Any steps in noradrenaline increase at least 0.2 ug/kg/min, or intensifying inotropic treatment (i.e. dose increasing or initiation of new agents) are considered treatment escalation, irrespective of trial arm. Uptitration of noradrenaline up to 0.2 ug/kg/min is considered standard of care. Treatment escalation also includes the initiation of MCS (including the institution of IABP in the standard of care-arm or escalation to e.g. continuous flow or extracorporeal mechanical circulatory support in the IABP-arm).	30-day follow-up
Secondary	Deterioration of SCAI stage B to C (percent)	If the patient entered the trial meeting criteria for SCAI stage B	30-day follow-up
Secondary	Deterioration of cardiogenic shock (percent)	Degradation to SCAI stage D or E	at 7 and 14 days after randomization
Secondary	Vascular complications defined according to VARC-3 guidelines (percent)	Following randomization to the IABP-arm, specifying major and minor vascular complications as well as major and minor access-related non-vascular complications	30-day follow-up
Secondary	Major bleeding complications defined according to BARC guidelines (at least type 2) (percent)	Following randomization to the IABP-arm	30-day follow-up
Secondary	De-novo Acute Coronary Syndrome (percent)	i.e. type 1 myocardial infarction	30-day and 1-year follow-up
Secondary	Cardiopulmonary resuscitation or defibrillation (percent)	Including an appropriate shock of an Implantable Cardioverter Defibrillator	30-day follow-up
Secondary	Development of SIRS, sepsis or severe sepsis (percent)	Defined according to the Surviving Sepsis Guidelines	96-hours after randomization