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

Study Overview
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Brief Summary
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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.

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

Conditions
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Cardiogenic Shock, Myocardial Infarction

Intervention / Treatment
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* Drug: Reduced noradrenaline use


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reduced noradrenaline (MAP ≥ 55 mmHg)<br> | Drug: Reduced noradrenaline use<br>* Reduced noradrenaline by using a lower MAP target<br>|
| No Intervention: Usual care (MAP ≥ 65 mmHg)<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality and renal failure | Composite of all-cause mortality and severe renal failure leading to renal replacement therapy | 30-days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure (systolic and diastolic) | Blood pressure measured hourly during the first 24 hours of ICU/CCU admission | The first 24 hours | 
| Heart rate | Heart rate, measured hourly during the first 24 hours of ICU/CCU admission | The first 24 hours | 
| Enzymatic infarct size, measured by hs-Troponin T | Size of myocardial infarction, measured by hs-Troponin T | 0, 6, 12, 24, 36 and 72 hours | 
| Enzymatic infarct size, measured by CK-MB | Size of myocardial infarction, measured by CK-MB | 0, 6, 12, 24, 36 and 72 hours | 
| Need for mechanical circulatory support | Type of mechanical circulatory support device | Recorded after ICU/CCU discharge, assessed up to 60 days | 
| Duration of mechanical ventilation | Duration of mechanical ventilation, expressed in days | Recorded after ICU/CCU discharge, assessed up to 60 days | 
| Need for vasopressors / inotropes | The type of vasopressors / inotropes that were administrered | Recorded after ICU/CCU discharge, assessed up to 60 days | 
| Ejection fraction, percent | As measured by echocardiography and/or MRI | 72 hours and 1 year | 
| Renal function | Renal function, measured by serum creatinin | 1 year | 
| Cost-effectiveness | Cost per patients alive without severe renal failure and costs per QALY (quality-adjusted life year) | 1-year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Noradrenaline, Blood pressure target, Cardiogenic shock, Myocardial infarction