Clinical Outcome and Cost-effectiveness of Reduced Noradrenaline by Using a Lower Blood Pressure Target in Patients With Cardiogenic Shock From Acute Myocardial Infarction

Overview

Rationale: Pump failure due to acute myocardial infarction (AMI) can lead to cardiogenic shock (CS): a state of low blood flow to end-organs with subsequent multi-organ failure that is associated with high mortality rated. The first line pharmacologic treatment strategy in CS is noradrenaline. This vasopressor drug is used to maintain adequate blood pressures. The assumption is that a mean arterial blood pressure (MAP) ≥ 65 mmHg will improve flow and thereby tissue perfusion of myocardium and other tissues (e.g. renal). However, there is no evidence that an increase in MAP, if achieved by noradrenaline, leads to greater end-organ blood flow and better outcomes. Objective: With this study the investigators aim to investigate the (cost-)effectiveness of reduced noradrenaline in patients with CS by using a lower MAP target of ≥ 55 mmHg, compared to ≥ 65 mmHg. The investigators hypothesize that reduced use of noradrenaline will improve overall survival and decrease renal failure requiring renal replacement therapy. Study design: Open label, randomized controlled multicenter trial Study population: Adults patients with CS due to AMI Intervention: Treatment strategy of reduced noradrenaline, by using a lower MAP target ( ≥ 55 mmHg). Main study endpoint: composite of all-cause mortality and severe renal failure leading to renal replacement therapy within 30-days after randomization.

Interventions

• Drug Reduced noradrenaline use
  Reduced noradrenaline by using a lower MAP target

Primary outcome measures

• Mortality and renal failure [Time frame: 30-days]

Secondary outcome measures (10)

• Blood pressure (systolic and diastolic) [Time frame: The first 24 hours]
• Heart rate [Time frame: The first 24 hours]
• Enzymatic infarct size, measured by hs-Troponin T [Time frame: 0, 6, 12, 24, 36 and 72 hours]
• Enzymatic infarct size, measured by CK-MB [Time frame: 0, 6, 12, 24, 36 and 72 hours]
• Need for mechanical circulatory support [Time frame: Recorded after ICU/CCU discharge, assessed up to 60 days]
• Duration of mechanical ventilation [Time frame: Recorded after ICU/CCU discharge, assessed up to 60 days]
• Need for vasopressors / inotropes [Time frame: Recorded after ICU/CCU discharge, assessed up to 60 days]
• Ejection fraction, percent [Time frame: 72 hours and 1 year]
• Renal function [Time frame: 1 year]
• Cost-effectiveness [Time frame: 1-year]

Eligibility criteria

Inclusion criteria

• Acute myocardial infarction, STEMI or NSTEMI
• Early revascularization by PCI
• Cardiogenic shock, characterized by:

I. a. Systolic blood pressure (SBP) ≤ 90 mmHg for > 30 minutes, OR b. Use of drugs to maintain SBP > 90 mmHg at randomization.

II. Clinical signs of impaired organ perfusion with at least one of the following criteria:

• Altered mental status
• Cold, clammy skin and extremities
• Oliguria with urine output < 30ml/hour
• Serum lactate > 2.0 mmol/L

III. Clinical signs of pulmonary congestion

Exclusion criteria

• Resuscitation > 30 minutes
• Mechanical cause of cardiogenic shock (e.g. papillary muscle rupture, ventricular septal rupture)
• Onset of shock > 12 hours
• Imminent need for mechanical circulatory support (i.e. ECPR)
• Women <45 years

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Netherlands · 1 center

• Amsterdam UMC, location AMC — Amsterdam

Identifiers

NCT: NCT05168462 · NL79416.018.21

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗