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

University Hospital, Tours1,010 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

1,010

Conditions

Acute Circulatory Failure

Interventions

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 strategyPROCEDURE

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 Years

Medical Language ↔ Plain English

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

Locations (9)

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, France

Outcomes

Primary Outcomes

All-cause mortality by 28 days after randomisation

Time frame: Patients will be followed from randomization to day 28

Secondary Outcomes

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

Cumulative incidence of death

Time frame: From inclusion through Day 90

Cumulative survival free of indwelling arterial catheter insertion

Time frame: From inclusion through Day 90

Number of patients who underwent indwelling arterial catheter insertion, in both groups

Time frame: From randomization to Day 28

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.

Time frame: During the first seven days

Daily amount of intravenous fluid given for rapid vascular volume expansion

Time frame: From Day 1 to Day 7

Duration of mechanical ventilation

Time frame: From inclusion to Day 28

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

Time frame: From Day 1 to Day 28

Proportion of patients treated by renal-replacement therapy

Time frame: Between Day 1 and Day 28

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

Time frame: From Day 1 to Day 28

Proportion of patients treated by vasopressor

Time frame: Between Day 1 and Day 28

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

Time frame: From Day 1 to Day 28

Mean daily blood volume drawn for lab testing during intensive care unit stay

Time frame: From inclusion to Day 28

Number of blood cultures performed during intensive care unit stay

Time frame: From inclusion to Day 28

Number of attempts at arterial puncture during intensive care unit stay

Time frame: From inclusion to Day 28

Evolution of blood haemoglobin level

Time frame: From Day 1 to Day 28

Evolution of haematocrit

Time frame: From Day 1 to Day 28

Number of red blood cell packs transfused

Time frame: From Day 1 to Day 28

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

Time (min) spent by nurses and physicians (min) on these tasks

This outcome measure is planned to be collected during the first three days in a random sample of 10% of the study population and will be only considered during the medico-economic analyses.

Time frame: During the first three days of the intensive care unit stay

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.

Time frame: From inclusion to Day 28

Numbers of arterial and central venous catheter-related infections

Number of new cases per 1000 catheter-days

Time frame: During intensive care unit stay

Numbers of local infections of arterial and central venous

Number of new cases per 1000 catheter-days

Time frame: During intensive care unit stay

Numbers of arterial and central venous catheter-related bloodstream infections

Number of new cases per 1000 catheter-days

Time frame: During intensive care unit stay

Number of bloodstream infections

Time frame: During intensive care unit stay

Duration of intensive care unit stay

Time frame: From inclusion to discharge

Duration of hospital stay

Time frame: From inclusion to discharge

Intensive care unit mortality

Time frame: From inclusion to discharge

Hospital mortality

Time frame: From inclusion to discharge

Day 90 mortality

Time frame: Day 90

Number of Adverse Events of special interest

Time frame: From inclusion to Day 90

Incremental Cost-Effectiveness Ratio

Time frame: At Day 28

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

Time frame: on a 5 years' time frame

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).

Time frame: Once a day, from inclusion to Day 28

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).

Time frame: One a day, from inclusion to Day 28

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)

Time frame: The first seven days