Early Versus Differed Arterial Catheterization in Critically Ill Patients With Acute Circulatory Failure:

Acute Circulatory Failure Clinical Trial

— EVERDAC  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03680963
• Other study ID #: DR180137
• Status: Completed
• Phase: N/A
• Start date: November 15, 2018
• Est. completion date: February 28, 2023

Study information

• Verified date: November 2023
• Source: University Hospital, Tours
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1010
• Est. completion date: February 28, 2023
• Est. primary completion date: November 29, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Circulatory Failure
• Shock

Intervention

Procedure:
• Non-invasive strategy
No indwelling arterial catheter insertion will be allowed during the first 28 days, excepted if predefined safety criteria (indicating absolute need of indwelling arterial catheter insertion) are reached. In the "non-invasive" group, automated oscillometric monitor will be used to monitor BP (blood pressure).
• Control strategy
An indwelling arterial catheter will be inserted as soon as possible (within the first four hours after randomization) and will be maintained except in case of indwelling arterial catheter futility, suspected or proven indwelling arterial catheter related infection or thrombosis (at discretion of attending physician) until day 28 or ICU (Intensive Care Unit) discharge (whichever comes first). After day 28, clinicians may choose to maintain or to remove indwelling arterial catheter.

Locations

Country	Name	City	State
France	Intensive care	Argenteuil
France	Intensive care	Dijon
France	Intensive care	La Roche-sur-Yon
France	Intensive care	Montauban
France	Intensive care	Nantes
France	Intensive care	Orléans
France	Intensive care	Poitiers
France	Intensive care	Strasbourg
France	Intensive care	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Tours

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause mortality by 28 days after randomisation		Patients will be followed from randomization to day 28
Secondary	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		From inclusion to Day 35
Secondary	Cumulative incidence of death		From inclusion through Day 90
Secondary	Cumulative survival free of indwelling arterial catheter insertion		From inclusion through Day 90
Secondary	Number of patients who underwent indwelling arterial catheter insertion, in both groups		From randomization to Day 28
Secondary	Evolution of daily Sequential Organ Failure Assessment (SOFA) score	The score (ranged from 0 to 24, the worth outcome) is based on six sub-scores (each ranged from 0 to 4, the worth outcome), one for each respiratory system, neurological, cardiovascular, hepatic, renal and coagulation.	During the first seven days
Secondary	Daily amount of intravenous fluid given for rapid vascular volume expansion		From Day 1 to Day 7
Secondary	Duration of mechanical ventilation		From inclusion to Day 28
Secondary	Ventilator-free days	Patients dying between randomisation and Day 28 will be assigned a 0 value; for survivors at Day 28, all the days free of invasive mechanical ventilation through an endotracheal tube within the 28-day period will be taken into account	From Day 1 to Day 28
Secondary	Proportion of patients treated by renal-replacement therapy		Between Day 1 and Day 28
Secondary	Renal replacement therapy-free days	Days without renal replacement therapy from Day 1 to Day 28 for survivors at Day 28, and from Day 1 to the date of death for patients dying before Day 28, will be taken into account	From Day 1 to Day 28
Secondary	Proportion of patients treated by vasopressor		Between Day 1 and Day 28
Secondary	Vasopressor therapy-free days	Days without vasopressor therapy from Day 1 to Day 28 for survivors at Day 28, and from Day 1 to the date of death for patients dying before Day 28, will be taken into account	From Day 1 to Day 28
Secondary	Mean daily blood volume drawn for lab testing during intensive care unit stay		From inclusion to Day 28
Secondary	Number of blood cultures performed during intensive care unit stay		From inclusion to Day 28
Secondary	Number of attempts at arterial puncture during intensive care unit stay		From inclusion to Day 28
Secondary	Evolution of blood haemoglobin level		From Day 1 to Day 28
Secondary	Evolution of haematocrit		From Day 1 to Day 28
Secondary	Number of red blood cell packs transfused		From Day 1 to Day 28
Secondary	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		From inclusion to Day 28
Secondary	Time (min) spent by nurses and physicians (min) on these tasks		During the first three days of the intensive care unit stay
Secondary	Number of arterial and central venous catheter insertion during intensive care unit stay	Expressed as the incidence of new cases per 1000 catheter-days, including local and catheter-related bloodstream infections as consensually defined.	From inclusion to Day 28
Secondary	Numbers of arterial and central venous catheter-related infections	Number of new cases per 1000 catheter-days	During intensive care unit stay
Secondary	Numbers of local infections of arterial and central venous	Number of new cases per 1000 catheter-days	During intensive care unit stay
Secondary	Numbers of arterial and central venous catheter-related bloodstream infections	Number of new cases per 1000 catheter-days	During intensive care unit stay
Secondary	Number of bloodstream infections		During intensive care unit stay
Secondary	Duration of intensive care unit stay		From inclusion to discharge
Secondary	Duration of hospital stay		From inclusion to discharge
Secondary	Intensive care unit mortality		From inclusion to discharge
Secondary	Hospital mortality		From inclusion to discharge
Secondary	Day 90 mortality		Day 90
Secondary	Number of Adverse Events of special interest		From inclusion to Day 90
Secondary	Incremental Cost-Effectiveness Ratio		At Day 28
Secondary	Budget impact analysis of the generalization of the non-invasive strategy	The budget impact analysis will be to multiply the average annual cost per patient over 5 years by the number of eligible patients, taking into account a penetration rate	on a 5 years' time frame
Secondary	Pain related to the device used for blood pressure monitoring	Numerical scale assessment of patient-reported pain related to the device used for blood pressure monitoring.; Using the following 11-point numerical scales, ranged from 0 (no pain) to 10 (very important and permanent pain).	Once a day, from inclusion to Day 28
Secondary	Discomfort related to device used for blood pressure monitoring	Numerical scale assessment of patient-reported discomfort related to the device used for blood pressure monitoring Using the following 11-point numerical scales, ranged from 0 (no discomfort) to 10 (very important and permanent discomfort).	One a day, from inclusion to Day 28
Secondary	Daily fluid balance of intakes and loss	Difference between the daily amounts of: daily fluid administration (in milliliter): intravenous hydration, vascular filling, enteral hydration; and the daily fluid loss (in milliliter): urine and fluid removal (during renal replacement therapy), tube drainage, estimated blood loss (laboratory test, bleeding)	The first seven days