Back to resultsEarly Versus Differed Arterial Catheterization in Critically Ill Patients With Acute Circulatory Failure: (EVERDAC)
Primary Purpose
Acute Circulatory Failure
Status
Active
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Non-invasive strategy
Control strategy
Sponsored by
About this trial
This is an interventional other trial for Acute Circulatory Failure
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:
- 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)
- 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
Sites / Locations
- Intensive care
- Intensive care
- Intensive care
- Intensive care
- Intensive care
- Intensive care
- Intensive care
- Intensive care
- Intensive care
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Non-invasive strategy
Control strategy
Arm Description
Non-invasive strategy consisting of blood pressure monitoring by non-invasive automated cuff measurements
Usual strategy of systematic indwelling arterial catheter insertion in the early hours of acute circulatory failure
Outcomes
Primary Outcome Measures
All-cause mortality by 28 days after randomisation
Secondary Outcome Measures
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
Cumulative incidence of death
Cumulative survival free of indwelling arterial catheter insertion
Number of patients who underwent indwelling arterial catheter insertion, in both groups
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.
Daily amount of intravenous fluid given for rapid vascular volume expansion
Duration of mechanical ventilation
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
Proportion of patients treated by renal-replacement therapy
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
Proportion of patients treated by vasopressor
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
Mean daily blood volume drawn for lab testing during intensive care unit stay
Number of blood cultures performed during intensive care unit stay
Number of attempts at arterial puncture during intensive care unit stay
Evolution of blood haemoglobin level
Evolution of haematocrit
Number of red blood cell packs transfused
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
Time (min) spent by nurses and physicians (min) on these tasks
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.
Numbers of arterial and central venous catheter-related infections
Number of new cases per 1000 catheter-days
Numbers of local infections of arterial and central venous
Number of new cases per 1000 catheter-days
Numbers of arterial and central venous catheter-related bloodstream infections
Number of new cases per 1000 catheter-days
Number of bloodstream infections
Duration of intensive care unit stay
Duration of hospital stay
Intensive care unit mortality
Hospital mortality
Day 90 mortality
Number of Adverse Events of special interest
Incremental Cost-Effectiveness Ratio
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
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).
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).
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)
Full Information
NCT ID
NCT03680963
First Posted
September 11, 2018
Last Updated
December 1, 2022
Sponsor
University Hospital, Tours
1. Study Identification
Unique Protocol Identification Number
NCT03680963
Brief Title
Early Versus Differed Arterial Catheterization in Critically Ill Patients With Acute Circulatory Failure:
Acronym
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)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 15, 2018 (Actual)
Primary Completion Date
November 29, 2022 (Actual)
Study Completion Date
March 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Tours
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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:
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%).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Circulatory Failure
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1010 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Non-invasive strategy
Arm Type
Experimental
Arm Description
Non-invasive strategy consisting of blood pressure monitoring by non-invasive automated cuff measurements
Arm Title
Control strategy
Arm Type
Other
Arm Description
Usual strategy of systematic indwelling arterial catheter insertion in the early hours of acute circulatory failure
Intervention Type
Procedure
Intervention Name(s)
Non-invasive strategy
Intervention Description
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).
Intervention Type
Procedure
Intervention Name(s)
Control strategy
Intervention Description
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.
Primary Outcome Measure Information:
Title
All-cause mortality by 28 days after randomisation
Time Frame
Patients will be followed from randomization to day 28
Secondary Outcome Measure Information:
Title
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
Time Frame
From inclusion to Day 35
Title
Cumulative incidence of death
Time Frame
From inclusion through Day 90
Title
Cumulative survival free of indwelling arterial catheter insertion
Time Frame
From inclusion through Day 90
Title
Number of patients who underwent indwelling arterial catheter insertion, in both groups
Time Frame
From randomization to Day 28
Title
Evolution of daily Sequential Organ Failure Assessment (SOFA) score
Description
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.
Time Frame
During the first seven days
Title
Daily amount of intravenous fluid given for rapid vascular volume expansion
Time Frame
From Day 1 to Day 7
Title
Duration of mechanical ventilation
Time Frame
From inclusion to Day 28
Title
Ventilator-free days
Description
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
Time Frame
From Day 1 to Day 28
Title
Proportion of patients treated by renal-replacement therapy
Time Frame
Between Day 1 and Day 28
Title
Renal replacement therapy-free days
Description
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
Time Frame
From Day 1 to Day 28
Title
Proportion of patients treated by vasopressor
Time Frame
Between Day 1 and Day 28
Title
Vasopressor therapy-free days
Description
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
Time Frame
From Day 1 to Day 28
Title
Mean daily blood volume drawn for lab testing during intensive care unit stay
Time Frame
From inclusion to Day 28
Title
Number of blood cultures performed during intensive care unit stay
Time Frame
From inclusion to Day 28
Title
Number of attempts at arterial puncture during intensive care unit stay
Time Frame
From inclusion to Day 28
Title
Evolution of blood haemoglobin level
Time Frame
From Day 1 to Day 28
Title
Evolution of haematocrit
Time Frame
From Day 1 to Day 28
Title
Number of red blood cell packs transfused
Time Frame
From Day 1 to Day 28
Title
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
Time Frame
From inclusion to Day 28
Title
Time (min) spent by nurses and physicians (min) on these tasks
Time Frame
During the first three days of the intensive care unit stay
Title
Number of arterial and central venous catheter insertion during intensive care unit stay
Description
Expressed as the incidence of new cases per 1000 catheter-days, including local and catheter-related bloodstream infections as consensually defined.
Time Frame
From inclusion to Day 28
Title
Numbers of arterial and central venous catheter-related infections
Description
Number of new cases per 1000 catheter-days
Time Frame
During intensive care unit stay
Title
Numbers of local infections of arterial and central venous
Description
Number of new cases per 1000 catheter-days
Time Frame
During intensive care unit stay
Title
Numbers of arterial and central venous catheter-related bloodstream infections
Description
Number of new cases per 1000 catheter-days
Time Frame
During intensive care unit stay
Title
Number of bloodstream infections
Time Frame
During intensive care unit stay
Title
Duration of intensive care unit stay
Time Frame
From inclusion to discharge
Title
Duration of hospital stay
Time Frame
From inclusion to discharge
Title
Intensive care unit mortality
Time Frame
From inclusion to discharge
Title
Hospital mortality
Time Frame
From inclusion to discharge
Title
Day 90 mortality
Time Frame
Day 90
Title
Number of Adverse Events of special interest
Time Frame
From inclusion to Day 90
Title
Incremental Cost-Effectiveness Ratio
Time Frame
At Day 28
Title
Budget impact analysis of the generalization of the non-invasive strategy
Description
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
Time Frame
on a 5 years' time frame
Title
Pain related to the device used for blood pressure monitoring
Description
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).
Time Frame
Once a day, from inclusion to Day 28
Title
Discomfort related to device used for blood pressure monitoring
Description
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).
Time Frame
One a day, from inclusion to Day 28
Title
Daily fluid balance of intakes and loss
Description
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)
Time Frame
The first seven days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
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:
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)
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Grégoire MULLER
Organizational Affiliation
UNIVERSITY HOSPITAL, ORLEANS
Official's Role
Principal Investigator
Facility Information:
Facility Name
Intensive care
City
Argenteuil
Country
France
Facility Name
Intensive care
City
Dijon
Country
France
Facility Name
Intensive care
City
La Roche-sur-Yon
Country
France
Facility Name
Intensive care
City
Montauban
Country
France
Facility Name
Intensive care
City
Nantes
Country
France
Facility Name
Intensive care
City
Orléans
Country
France
Facility Name
Intensive care
City
Poitiers
Country
France
Facility Name
Intensive care
City
Strasbourg
Country
France
Facility Name
Intensive care
City
Tours
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34521655
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.
Results Reference
derived
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Early Versus Differed Arterial Catheterization in Critically Ill Patients With Acute Circulatory Failure:
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