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

• ClinicalTrials.gov Identifier: NCT03680963
• Recruitment Status: Recruiting
• First Posted: September 21, 2018
• Last Update Posted: April 30, 2021
• Sponsor: University Hospital, Tours
• Information provided by (Responsible Party): University Hospital, Tours

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:

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.

Condition or disease	Intervention/treatment	Phase
Acute Circulatory Failure	Procedure: Non-invasive strategy; Procedure: Control strategy	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1010 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• 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)
• Actual Study Start Date: November 15, 2018
• Estimated Primary Completion Date: November 2021
• Estimated Study Completion Date: November 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Non-invasive strategy; Non-invasive strategy consisting of blood pressure monitoring by non-invasive automated cuff measurements	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; Usual strategy of systematic indwelling arterial catheter insertion in the early hours of acute circulatory failure	Procedure: 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.

Outcome Measures

Primary Outcome Measures :

1. All-cause mortality by 28 days after randomisation [ Time Frame: Patients will be followed from randomization to day 28 ]

Secondary Outcome Measures :

1. 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 ]
2. Cumulative incidence of death [ Time Frame: From inclusion through Day 90 ]
3. Cumulative survival free of indwelling arterial catheter insertion [ Time Frame: From inclusion through Day 90 ]
4. Number of patients who underwent indwelling arterial catheter insertion, in both groups [ Time Frame: From randomization to Day 28 ]
5. Evolution of daily Sequential Organ Failure Assessment (SOFA) score [ Time Frame: During the first seven days ]
   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.
6. Daily amount of intravenous fluid given for rapid vascular volume expansion [ Time Frame: From Day 1 to Day 7 ]
7. Duration of mechanical ventilation [ Time Frame: From inclusion to Day 28 ]
8. Ventilator-free days [ Time Frame: From Day 1 to Day 28 ]
   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
9. Proportion of patients treated by renal-replacement therapy [ Time Frame: Between Day 1 and Day 28 ]
10. Renal replacement therapy-free days [ Time Frame: From Day 1 to Day 28 ]
    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
11. Proportion of patients treated by vasopressor [ Time Frame: Between Day 1 and Day 28 ]
12. Vasopressor therapy-free days [ Time Frame: From Day 1 to Day 28 ]
    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
13. Mean daily blood volume drawn for lab testing during intensive care unit stay [ Time Frame: From inclusion to Day 28 ]
14. Number of blood cultures performed during intensive care unit stay [ Time Frame: From inclusion to Day 28 ]
15. Number of attempts at arterial puncture during intensive care unit stay [ Time Frame: From inclusion to Day 28 ]
16. Evolution of blood haemoglobin level [ Time Frame: From Day 1 to Day 28 ]
17. Evolution of haematocrit [ Time Frame: From Day 1 to Day 28 ]
18. Number of red blood cell packs transfused [ Time Frame: From Day 1 to Day 28 ]
19. 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 ]
20. Time (min) spent by nurses and physicians (min) on these tasks [ Time Frame: During the first three days of the intensive care unit stay ]
21. Number of arterial and central venous catheter insertion during intensive care unit stay [ Time Frame: From inclusion to Day 28 ]
    Expressed as the incidence of new cases per 1000 catheter-days, including local and catheter-related bloodstream infections as consensually defined.
22. Numbers of arterial and central venous catheter-related infections [ Time Frame: During intensive care unit stay ]
    Number of new cases per 1000 catheter-days
23. Numbers of local infections of arterial and central venous [ Time Frame: During intensive care unit stay ]
    Number of new cases per 1000 catheter-days
24. Numbers of arterial and central venous catheter-related bloodstream infections [ Time Frame: During intensive care unit stay ]
    Number of new cases per 1000 catheter-days
25. Number of bloodstream infections [ Time Frame: During intensive care unit stay ]
26. Duration of intensive care unit stay [ Time Frame: From inclusion to discharge ]
27. Duration of hospital stay [ Time Frame: From inclusion to discharge ]
28. Intensive care unit mortality [ Time Frame: From inclusion to discharge ]
29. Hospital mortality [ Time Frame: From inclusion to discharge ]
30. Day 90 mortality [ Time Frame: Day 90 ]
31. Number of Adverse Events of special interest [ Time Frame: From inclusion to Day 90 ]
32. Incremental Cost-Effectiveness Ratio [ Time Frame: At Day 28 ]
33. Budget impact analysis of the generalization of the non-invasive strategy [ Time Frame: on a 5 years' time frame ]
    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
34. Pain related to the device used for blood pressure monitoring [ Time Frame: Once a day, from inclusion to Day 28 ]

    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).

35. Discomfort related to device used for blood pressure monitoring [ Time Frame: One a day, from inclusion to Day 28 ]
    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).
36. Daily fluid balance of intakes and loss [ Time Frame: The first seven days ]

    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)

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: Grégoire MULLER, MD; +33 238 514 446; muller.gregoire.chro@gmail.com

Contact: Marie LECLERC; +33(0)2.47.47.46.64; m.leclerc@chu-tours.fr

Locations

France

Intensive care; Withdrawn

Angoulême, France

Intensive care; Recruiting

Argenteuil, France

Contact: Damien CONTOU, MD

Principal Investigator: Damien CONTOU

Intensive care; Recruiting

Dijon, France

Contact: Jean-Pierre QUENOT

Principal Investigator: Jean-Pierre QUENOT

Intensive care; Recruiting

La Roche-sur-Yon, France

Contact: Marie-Ange AZAIS, MD

Principal Investigator: Marie-Ange AZAIS, MD

Intensive care; Withdrawn

La Réunion, France

Intensive care; Recruiting

Montauban, France

Contact: Sylvie VIMEUX, MD

Principal Investigator: Sylvie VIMEUX

Intensive care; Recruiting

Nantes, France

Contact: Maelle MARTIN, MD

Principal Investigator: Maelle MARTIN

Intensive care; Recruiting

Orléans, France

Contact: Thierry BOULAIN, MD

Principal Investigator: Thierry BOULAIN

Intensive care; Recruiting

Poitiers, France

Contact: Florence BOISSIER, MD

Principal Investigator: Florence BOISSIER

Intensive care; Recruiting

Strasbourg, France

Contact: Alexandra MONNIER

Principal Investigator: Alexandra MONNIER

Intensive care; Recruiting

Tours, France

Contact: Stephan EHRMANN

Principal Investigator: Stephan EHRMANN

Sponsors and Collaborators

University Hospital, Tours

Investigators

• Principal Investigator: Grégoire MULLER; UNIVERSITY HOSPITAL, ORLEANS

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University Hospital, Tours
• ClinicalTrials.gov Identifier: NCT03680963
• Other Study ID Numbers: DR180137
• First Posted: September 21, 2018
• Last Update Posted: April 30, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Shock; Pathologic Processes