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

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.

Study Overview

• Status: Recruiting
• Conditions: Myocardial Infarction; Cardiogenic Shock
• Intervention / Treatment: Drug: Reduced noradrenaline use

• Study Type: Interventional
• Enrollment (Anticipated): 776
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Elma Peters; Phone Number: 0205668380; Email: e.j.peters@amsterdamumc.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105AZ
    • Recruiting
    • Amsterdam UMC, location AMC
    • Contact: Jose Henriques; Email: j.p.henriques@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Acute myocardial infarction, STEMI or NSTEMI
2. Early revascularization by PCI
3. 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:

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

III. Clinical signs of pulmonary congestion

Exclusion Criteria:

1. Resuscitation > 30 minutes
2. Mechanical cause of cardiogenic shock (e.g. papillary muscle rupture, ventricular septal rupture)
3. Onset of shock > 12 hours
4. Imminent need for mechanical circulatory support

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reduced noradrenaline (MAP ≥ 55 mmHg)	Drug: Reduced noradrenaline use; Reduced noradrenaline by using a lower MAP target
No Intervention: Usual care (MAP ≥ 65 mmHg)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Anticipated): June 1, 2025
• Study Completion (Anticipated): June 1, 2026

Study Registration Dates

• First Submitted: November 8, 2021
• First Submitted That Met QC Criteria: December 7, 2021
• First Posted (Actual): December 23, 2021

Study Record Updates

• Last Update Posted (Actual): February 24, 2023
• Last Update Submitted That Met QC Criteria: February 23, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Myocardial infarction; Noradrenaline; Cardiogenic shock; Blood pressure target
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Shock; Hypotension; Shock, Cardiogenic; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine
• Other Study ID Numbers: NL79416.018.21

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No