Preventing Cardiovascular Collapse With Vasopressors During Tracheal Intubation (PREVENTION)

Preventing Cardiovascular Collapse With Vasopressors During Tracheal Intubation. The PREVENTION Randomized Multicenter Study

Tracheal intubation (TI) is associated with a high risk of adverse events in critically ill patients and peri-intubation hemodynamic collapse is the most commonly observed. The primary aim of the PREVENTION trial is to compare the effect of the pre-emptive use of noradrenaline versus no peri-intubation use of noradrenaline on incidence of cardiovascular collapse following TI in adult critically ill patients. Patients with absolute indication or contraindication to vasopressor support will be excluded from this trial. Patients will be randomized 1:1 to a continuous infusion of noradrenaline started before induction titrated according to baseline mean arterial pressure. The primary outcome will be the incidence of cardiovascular collapse. Secondary outcomes will include lowest systolic blood pressure and cardiac arrest within 30 minutes from intubation.

Study Overview

• Status: Not yet recruiting
• Conditions: Critical Illness; Respiratory Failure
• Intervention / Treatment: Drug: Noradrenaline

Detailed Description

PREVENTION trial is a pragmatic, multi-center, un-blinded, parallel group, randomized study comparing the pre-emptive use of noradrenaline to no-vasopressors during the peri-intubation period of adult critically ill patients. Investigators hypothesize that the pre-emptive administration of noradrenaline would mitigate the incidence and severity of peri-intubation cardiovascular collapse. The study will include adult (18 yrs or older) critically ill patients needing in-hospital intubation, excluding patients with absolute indication or contraindication to vasopressors. Patients will be randomized to receive either a continuous infusion of noradrenaline started at least 8 minutes before induction vs no vasopressors during the peri-intubation period. All co-interventions will be provided according to clinician's judgement. The primary outcome of the study will be a composite of MAP < 60 mmHg or cardiac arrest. Secondary outcomes will include lowest systolic blood pressure < 30 minutes from induction, change in systolic blood pressure from baseline to the lowest value within 30 minutes from induction and cardiac arrest.

• Study Type: Interventional
• Enrollment (Estimated): 420
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Vincenzo Russotto, MD; Phone Number: +393297893044; Email: vincenzo.russotto@unito.it
• Study Contact Backup: Name: Antonella Vasamì; Email: antonella.vasami@marionegri.it

Study Locations

• France
  • Nantes, France
    • CHU de Nantes
    • Contact: Jean Baptiste Lascarrou, MD, PhD
• Ireland
  • Galway, Ireland
    • Galway University Hospitals
    • Contact: John G Laffey, MD
• Italy
  • Turin
    • Orbassano, Turin, Italy, 10043
      • University Hospital San Luigi Gonzaga
      • Contact: Vincenzo Russotto, MD; Email: vincenzo.russotto@unito.it
      • Contact: Pietro Caironi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient is admitted or scheduled for admission to a participating study hospital
• Planned procedure is tracheal intubation and planned operator is a provider expected to routinely perform endotracheal intubation in the participating unit
• Critical illness (i.e. life-threatening condition with intubation required for cardiorespiratory failure or neurological impairment)
• Administration of sedation (with or without neuromuscular blockade) is planned
• Age 18 years or older

Exclusion Criteria:

• No vasopressors/inotropes at the moment of screening for eligibility
• MAP < 60 mmHg or > 120 mmHg at the moment of screening for eligibility
• Urgency of intubation precludes safe performance of study procedures
• Intubation performed during cardiopulmonary resuscitation of a patient in cardiac arrest
• Enrolled in another clinical trial that is unapproved for co-enrollment
• Pregnant or suspected pregnancy

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: Pre-emptive vasopressor; Pre-emptive continuous infusion of norepinephrine during intubation	Drug: Noradrenaline; Pre-emptive continuous infusion of noradrenaline during the peri-intubation period; Other Names: Norepinephrine
No Intervention: No vasopressor; No pre-emptive administration of vasopressors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with cardiovascular collapse	Composite outcome of mean arterial pressure < 60 mmHg or cardiac arrest	30 minutes from induction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with MAP < 60 mmHg	Mean arterial pressure < 60 mmHg	30 minutes from induction
Number of patients with cardiac arrest	Development of either a shockable or non shockable rhythm associated with cardiac arrest	30 minutes from induction
Lowest value of SBP	Lowest systolic blood pressure	30 minutes from induction
Change in SBP value from last value before induction to lowest value	Drop of the systolic blood pressure from baseline value to the lowest value registered by 30 minutes from induction	30 minutes from induction
Need for a rescue vasopressor	Any unplanned administration of a vasopressor (either as bolus or continuous infusion)	30 minutes from induction
Number of patients with severe hypertension	Mean arterial pressure > 120 mmHg	30 minutes from induction

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with bradycardia	Heart rate < 60 beats per minute	30 minutes from induction
Number of patients with cardiac arrhythmias	Any ventricular or supraventricular arrhythmia	30 minutes from induction
Signs of tissue/peripheral ischemia at noradrenaline infusion site	Any sign of tissue/limb ischemia in case of peripheral vein infusion of noradrenaline	24 hours
Need for new start of renal replacement therapy	Need to start either continuous or intermittent renal replacement therapy	28 days from intubation
Total amount of fluid administered (ml)	Cumulative volume of fluids (ml)	30 minutes from induction
First pass intubation success	Confirmed intubation after a single attempt of laryngoscopy	30 minutes from induction
Total amount of rescue vasopressors after induction	Cumulative dose of any vasopressor administered either as a bolus or continuous infusion	30 minutes from induction
ICU-free days	Total number of days outside the ICU up to 28 days	28 days from intubation
Ventilator-free days	Total number of days free from invasive mechanical ventilation	28 days from intubation
Vasopressor-free days	Total number of days free from any vasopressor administration	28 days from intubation
In-hospital mortality	Death during the hospital admission up to 28 days	28 days from intubation

Collaborators and Investigators

• Sponsor: University of Turin, Italy
• Collaborators: Istituto Di Ricerche Farmacologiche Mario Negri
• Investigators: Study Chair: John G Laffey, MD, University Hospital Galway, NUI Galway, Ireland; Principal Investigator: Vincenzo Russotto, MD, University Hospital San Luigi Gonzaga

Publications and helpful links

General Publications

• Russotto V, Myatra SN, Laffey JG, Tassistro E, Antolini L, Bauer P, Lascarrou JB, Szuldrzynski K, Camporota L, Pelosi P, Sorbello M, Higgs A, Greif R, Putensen C, Agvald-Ohman C, Chalkias A, Bokums K, Brewster D, Rossi E, Fumagalli R, Pesenti A, Foti G, Bellani G; INTUBE Study Investigators. Intubation Practices and Adverse Peri-intubation Events in Critically Ill Patients From 29 Countries. JAMA. 2021 Mar 23;325(12):1164-1172. doi: 10.1001/jama.2021.1727. Erratum In: JAMA. 2021 May 24;:null.
• Russotto V, Myatra SN, Laffey JG. What's new in airway management of the critically ill. Intensive Care Med. 2019 Nov;45(11):1615-1618. doi: 10.1007/s00134-019-05757-0. Epub 2019 Sep 16. No abstract available.
• Janz DR, Casey JD, Semler MW, Russell DW, Dargin J, Vonderhaar DJ, Dischert KM, West JR, Stempek S, Wozniak J, Caputo N, Heideman BE, Zouk AN, Gulati S, Stigler WS, Bentov I, Joffe AM, Rice TW; PrePARE Investigators; Pragmatic Critical Care Research Group. Effect of a fluid bolus on cardiovascular collapse among critically ill adults undergoing tracheal intubation (PrePARE): a randomised controlled trial. Lancet Respir Med. 2019 Dec;7(12):1039-1047. doi: 10.1016/S2213-2600(19)30246-2. Epub 2019 Oct 1.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: August 10, 2021
• First Submitted That Met QC Criteria: August 14, 2021
• First Posted (Actual): August 20, 2021

Study Record Updates

• Last Update Posted (Actual): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: tracheal intubation
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Disease Attributes; Respiratory Insufficiency; Shock; Critical Illness; 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: PREVENTION

Drug and device information, study documents

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