Clinical trial NCT03680963: Early Versus Differed Arterial Catheterization in Critically Ill Patients With Acute Circulatory Failure:
Official title: Early Versus Differed Arterial Catheterization in Critically Ill Patients With Acute Circulatory Failure: A Multicentre, Open-label, Pragmatic, Randomised, Non-inferiority Controlled Trial (EVERDAC Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Circulatory Failure
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
First posted: 2018-09-21
Enrollment: 1010
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: OTHER

Brief summary: The objective of the present research is a combination of a one-sided test of non-inferiority and a one-sided test of superiority. A stepped approach will be used to evaluate these hypotheses:

1. a less invasive intervention (i.e., no indwelling arterial catheter insertion until felt absolutely needed, according to consensual and predefined safety criteria) is non inferior to usual care (i.e., systematic indwelling arterial catheter insertion in the early hours of shock) in terms of mortality at day 28 (non-inferiority margin of 5%).
2. a less invasive intervention is not only non-inferior but also superior to usual care in terms of mortality.

Multi-centre, pragmatic, randomised, controlled, open, two-parallel group, non-inferiority clinical trial.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years the day of inclusion
* Existence of an acute circulatory failure defined by the presence of the following items 1 and 2:

  1. Persisting hypotension (systolic blood pressure less than 90 mmHg or mean arterial blood pressure less than 65 mmHg) for more than 15 min at intensive care unit admission or within the following 24 hours, OR requirement of continuous intravenous vasopressor treatment (i.e. any dose of norepinephrine / epinephrine)
  2. Presence at least one of the following signs of hypoperfusion: alteration of mental status; skin mottling; oliguria defined as a urine output \< 0.5 mL/kg body weight for at least one hour; arterial lactate \> 2 mmol/L; peripheral venous lactate \> 3.2 mmol/L; ScvO2 \<70%
* Free express oral and informed consent of the patient or a proxy in case of impossibility for the patient to consent; emergency inclusion possible when legal representatives and patient's family are not available
* French health insurance holder

Exclusion Criteria:

* Acute circulatory failure, as defined by items 1 and 2 in inclusion criteria list (cf. supra) present for more than 24 hours
* Non invasive blood pressure (NIBP) device fails to display a blood pressure value, or cuff placement impossible
* Patient for whom an Extra-Corporeal Membrane Oxygenation (ECMO) therapy (either veno-arterial or venous-venous) is already in place or is to be initiated within the next 6 hours
* Patient treated with vasopressor doses of more than 2.5 μg/kg/min of norepinephrine tartrate plus epinephrine for at least 2 hours (i.e., for instance, more than 8 mg of norepinephrine tartrate in 50 mL at the rate of 66 mL/hour for a patient weighing 70 kg) (please note that in fact this dosage corresponds to 1.25 μg/kg/min of norepinephrine base)
* Severe traumatic brain injury (i.e., traumatic brain injury with a Glasgow coma scale score of less than 9 before sedation)
* Patient previously included in the trial
* Body mass index (BMI) above 40 kg/m2
* Pregnancy
* Brain death
* Moribund patient
* Patient known, at time of inclusion, as being under guardianship, authorship or curators

Primary outcomes:
measure: All-cause mortality by 28 days after randomisation
timeFrame: Patients will be followed from randomization to day 28
Secondary outcomes:
measure: To account for the potential bias brought by deaths occurring as the result of life-sustaining treatments withdrawal/withholding, as frequently encountered in intensive care unit, the investigators will record such events
timeFrame: From inclusion to Day 35
measure: Cumulative incidence of death
timeFrame: From inclusion through Day 90
measure: Cumulative survival free of indwelling arterial catheter insertion
timeFrame: From inclusion through Day 90
measure: Number of patients who underwent indwelling arterial catheter insertion, in both groups
timeFrame: From randomization to Day 28
measure: Evolution of daily Sequential Organ Failure Assessment (SOFA) score
timeFrame: During the first seven days
measure: Daily amount of intravenous fluid given for rapid vascular volume expansion
timeFrame: From Day 1 to Day 7
measure: Duration of mechanical ventilation
timeFrame: From inclusion to Day 28
measure: Ventilator-free days
timeFrame: From Day 1 to Day 28
measure: Proportion of patients treated by renal-replacement therapy
timeFrame: Between Day 1 and Day 28
measure: Renal replacement therapy-free days
timeFrame: From Day 1 to Day 28
measure: Proportion of patients treated by vasopressor
timeFrame: Between Day 1 and Day 28
measure: Vasopressor therapy-free days
timeFrame: From Day 1 to Day 28
measure: Mean daily blood volume drawn for lab testing during intensive care unit stay
timeFrame: From inclusion to Day 28
measure: Number of blood cultures performed during intensive care unit stay
timeFrame: From inclusion to Day 28
measure: Number of attempts at arterial puncture during intensive care unit stay
timeFrame: From inclusion to Day 28
measure: Evolution of blood haemoglobin level
timeFrame: From Day 1 to Day 28
measure: Evolution of haematocrit
timeFrame: From Day 1 to Day 28
measure: Number of red blood cell packs transfused
timeFrame: From Day 1 to Day 28
measure: Number of transcutaneous arterial and venous puncture for lab tests, arterial catheter insertion and set up of monitor, blood drawing from the arterial catheter or other vascular line
timeFrame: From inclusion to Day 28
measure: Time (min) spent by nurses and physicians (min) on these tasks
timeFrame: During the first three days of the intensive care unit stay
measure: Number of arterial and central venous catheter insertion during intensive care unit stay
timeFrame: From inclusion to Day 28
measure: Numbers of arterial and central venous catheter-related infections
timeFrame: During intensive care unit stay
measure: Numbers of local infections of arterial and central venous
timeFrame: During intensive care unit stay
measure: Numbers of arterial and central venous catheter-related bloodstream infections
timeFrame: During intensive care unit stay
measure: Number of bloodstream infections
timeFrame: During intensive care unit stay
measure: Duration of intensive care unit stay
timeFrame: From inclusion to discharge
measure: Duration of hospital stay
timeFrame: From inclusion to discharge
measure: Intensive care unit mortality
timeFrame: From inclusion to discharge
measure: Hospital mortality
timeFrame: From inclusion to discharge
measure: Day 90 mortality
timeFrame: Day 90
measure: Number of Adverse Events of special interest
timeFrame: From inclusion to Day 90
measure: Incremental Cost-Effectiveness Ratio
timeFrame: At Day 28
measure: Budget impact analysis of the generalization of the non-invasive strategy
timeFrame: on a 5 years' time frame
measure: Pain related to the device used for blood pressure monitoring
timeFrame: Once a day, from inclusion to Day 28
measure: Discomfort related to device used for blood pressure monitoring
timeFrame: One a day, from inclusion to Day 28
measure: Daily fluid balance of intakes and loss
timeFrame: The first seven days
Other outcomes:
Locations:
city: Argenteuil
country: France
facility: Intensive care
city: Dijon
country: France
facility: Intensive care
city: La Roche-sur-Yon
country: France
facility: Intensive care
city: Montauban
country: France
facility: Intensive care
city: Nantes
country: France
facility: Intensive care
city: Orléans
country: France
facility: Intensive care
city: Poitiers
country: France
facility: Intensive care
city: Strasbourg
country: France
facility: Intensive care
city: Tours
country: France
facility: Intensive care
Study officials:
affiliation: UNIVERSITY HOSPITAL, ORLEANS
name: Grégoire MULLER
role: PRINCIPAL_INVESTIGATOR
References:
citation: Muller G, Kamel T, Contou D, Ehrmann S, Martin M, Quenot JP, Lacherade JC, Boissier F, Monnier A, Vimeux S, Brunet Houdard S, Tavernier E, Boulain T. Early versus differed arterial catheterisation in critically ill patients with acute circulatory failure: a multicentre, open-label, pragmatic, randomised, non-inferiority controlled trial: the EVERDAC protocol. BMJ Open. 2021 Sep 14;11(9):e044719. doi: 10.1136/bmjopen-2020-044719.