Clinical trial NCT05014581: Preventing Cardiovascular Collapse With Vasopressors During Tracheal Intubation
Official title: Preventing Cardiovascular Collapse With Vasopressors During Tracheal Intubation. The PREVENTION Randomized Multicenter Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Critical Illness
Respiratory Failure
Keywords: tracheal intubation
Lead sponsor: University of Turin, Italy
Sponsor class: OTHER
Collaborators: name: Istituto Di Ricerche Farmacologiche Mario Negri
First posted: 2021-08-20
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with cardiovascular collapse
timeFrame: 30 minutes from induction
Secondary outcomes:
measure: Number of patients with cardiac arrest
timeFrame: 30 minutes from induction
measure: Number of patients with MAP < 60 mmHg
timeFrame: 30 minutes from induction
measure: Need for a rescue vasopressor
timeFrame: 30 minutes from induction
measure: Change in SBP value from last value before induction to lowest value
timeFrame: 30 minutes from induction
measure: Lowest value of SBP
timeFrame: 30 minutes from induction
measure: Number of patients with severe hypertension
timeFrame: 30 minutes from induction
Other outcomes:
measure: Number of patients with cardiac arrhythmias
timeFrame: 30 minutes from induction
measure: Number of patients with bradycardia
timeFrame: 30 minutes from induction
measure: Signs of tissue/peripheral ischemia at noradrenaline infusion site
timeFrame: 24 hours
measure: Need for new start of renal replacement therapy
timeFrame: 28 days from intubation
measure: Total amount of fluid administered (ml)
timeFrame: 30 minutes from induction
measure: First pass intubation success
timeFrame: 30 minutes from induction
measure: Total amount of rescue vasopressors after induction
timeFrame: 30 minutes from induction
measure: ICU-free days
timeFrame: 28 days from intubation
measure: Ventilator-free days
timeFrame: 28 days from intubation
measure: Vasopressor-free days
timeFrame: 28 days from intubation
measure: In-hospital mortality
timeFrame: 28 days from intubation
Locations:
city: Nantes
country: France
facility: CHU de Nantes
city: Galway
country: Ireland
facility: Galway University Hospitals
city: Rozzano
country: Italy
facility: Humanitas Research Hospital
state: Milan
city: Orbassano
country: Italy
facility: University Hospital San Luigi Gonzaga
state: Turin
city: Milan
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Milan
country: Italy
facility: Policlinico di Milano
Study officials:
affiliation: University Hospital San Luigi Gonzaga
name: Vincenzo Russotto, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Galway, NUI Galway, Ireland
name: John G Laffey, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.