Clinical trial NCT05188092: Lung Ultrasound-Guided Fluid Deresuscitation in ICU Patients
Official title: Effect of Lung Ultrasound-Guided Fluid Deresuscitation on Duration of Ventilation in Intensive Care Unit Patients (CONFIDENCE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Mechanical Ventilation
Fluid Overload
Deresuscitation
Ventilator-free Days
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2022-01-12
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Timely recognition and treatment of fluid overload can expedite liberation from invasive mechanical ventilation in intensive care unit (ICU) patients. Lung ultrasound (LUS) is an easy to learn, safe, cheap and noninvasive bedside imaging tool with high accuracy for pulmonary edema and pleural effusions in ICU patients. The aim of this study is to assess the effect of LUS-guided deresuscitation on duration of invasive ventilation in ICU patients. The investigators hypothesize that LUS-guided fluid deresuscitation is superior to routine fluid deresuscitation (not using LUS) with regard to duration of invasive ventilation.

This study is an international multicenter randomized clinical trial (RCT) in invasively ventilated ICU patients.This study will include 1,000 consecutively admitted invasively ventilated adult ICU patients, who are expected not to be extubated within the next 24 hours after randomization. Patients are randomly assigned to the intervention group, in which fluid deresuscitation is guided by repeated LUS, or the control group, in which fluid deresuscitation is at the discretion of the treating physician (not using LUS).

Detailed description: Objective:

The aim of this study is to assess the effect of LUS-guided deresuscitation on duration of invasive ventilation in ICU patients.

Hypothesis:

LUS-guided fluid deresuscitation is superior to routine fluid deresuscitation (not using LUS) with regard to duration of invasive ventilation.

Study design:

The CONFIDENCE study is an investigator-initiated, national, multicenter, randomized clinical trial in critically ill invasively ventilated patients admitted to the ICUs of participating hospitals.

Study population:

Adult patients admitted to ICUs in multiple countries

Sample size calculation:

The sample size is computed on the basis of the hypothesis that LUS guided deresuscitation is associated with a reduction of two days of ventilation. Assuming a mean (±SD) number of VFD-28 of 13±11 days, the ivenstigators estimate that a sample of 1000 patients (500 per group) is needed to have 80% power, at a two-tailed significance level of 0.05, to detect a mean between-group difference of 2 VFD-28, and allowing an anticipated dropout rate of 5%.

Methods:

Patients in participating intensive care units (ICU) are screened for eligibility. Inclusion and randomization will occur within 24 hours after meeting the inclusion criteria. If possible, informed consent from the legal representative will be obtained before randomization but no longer than 48 hours after meeting the inclusion criteria.

Patients are eligible if they are admitted to one of the participating ICUs, are invasively ventilated for less than 24 hours at randomization and expected to be under invasive ventilation for longer than 24 hours after randomization.

Randomization will be performed using Castor Electronic Data Capture (EDC). A dedicated, password protected, encrypted website. Randomization sequence is generated by a dedicated computer randomization software program. Due to the nature of the intervention, blinding of the caregivers is not possible.

Patients will be randomly assigned in a 1:1 ratio to lung guided fluid deresuscitation or routine fluid deresuscitation. Randomization will be stratified per center.

Lung ultrasound guided deresuscitation: with lung ultrasound (LUS)-guided fluid deresuscitation, LUS examinations are performed at least onze a day in hemodynamically stable patients, defined as a mean arterial pressure (MAP) ≥ 65 mmHg (with vasopressor dose decreasing and norepinephrine ≤ 0.2 μg/kg/min), and no new clear signs of hypoperfusion such as mottled skin and capillary refill time \> 3 seconds and/or new oliguria (urine output \< 0.3-0.5ml/kg/hour for the previous 6 hours). Target MAP can be changed in conditions in which 65 mmHg is not sufficient (i.e. history of chronic hypertension). In these cases the target MAP is at the discretion of the treating physician. 12-region LUS is performed, by a trained healthcare provider, and each region is scanned for the presence of B-lines and pleural effusions and scored using the lung ultrasound score. After extubation, lung ultrasound is continued once a day until day 28 or until discharge (whatever comes first) to monitor reappearance of pulmonary fluid overload or pleural effusion. In case of reappearance (or increase) of pulmonary fluid overload or pleural effusion, fluid withdrawal is started again according to the treatment protocol.

Routine deresuscitation: in routine fluid deresuscitation, in which fluid withdrawal is started and continued at the discretion of the treating physician, factors guiding fluid deresuscitation are chosen by the treating physician and may include the following: physical examination, laboratory values (e.g. BNP), chest x-ray, PiCCO or pulmonary artery catheters. LUS examinations are not performed to guide fluid deresuscitation in this group.

In both groups patients are extubated if standard extubation criteria are fulfilled, i.e., normal body temperature, patient awake and responsive/cooperative, adequate cough reflex, adequate oxygenation and ventilation, and hemodynamically stable.

Monitoring:

Monitoring of patients safety and reviewing of safety issues is performed by a designated independent Data Safety and Monitoring Board (DSMB).The DSMB watches over the ethics of conducting the study in accordance with the Declaration of Helsinki.

Eligibility criteria: Inclusion Criteria:

* Admission to one of the participating ICUs;
* Invasively ventilated for less than 24 hours at randomization;
* Expected to be under invasive ventilation for longer than 24 hours after randomization.

Exclusion Criteria:

* Age below 18 years old;
* Suspected or confirmed pregnancy;
* Participation in other interventional trials with similar endpoints;
* Use of long term home mechanical ventilation;
* Neurological condition that can prolong duration of mechanical ventilation (i.e.Guillain-Barré syndrome, high spinal cord lesion, amyotrophic lateral sclerosis, multiple sclerosis, or myasthenia gravis);
* Conditions in which LUS cannot be performed or correctly interpreted (i.e. chest wall abnormalities, morbid obesity, and pre-existing interstitial lung disease);
* Conditions in which targeting a negative fluid balance is discouraged (i.e. subarachnoid bleeding, severe rhabdomyolysis (CK \> 20.000);
* Previous participation in this RCT;
* Patients transferred from another center and invasively ventilated for longer than 24 hours.

Primary outcomes:
measure: Ventilator free days(VFD) and alive at day 28
timeFrame: 28 days after randomisation
Secondary outcomes:
measure: Duration of ventilation
timeFrame: 28 days
measure: ICU length of stay
timeFrame: 28 days
measure: Hospital length of stay
timeFrame: 28 days
measure: 28 day mortality
timeFrame: 28 days
measure: 90 day mortality
timeFrame: 90 days
measure: Incidences of reintubations
timeFrame: 28 days
measure: Cumulative fluid balances after randomization
timeFrame: 7 days
measure: Cumulative fluid balances after start of lung ultrasound examination
timeFrame: 7 days
measure: Incidence of acute kidney injury
timeFrame: 28 days
Other outcomes:
Locations:
city: Arnhem
country: Netherlands
facility: Rijnstate
state: Gelderland
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location AMC
state: Noord Holland
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location VUMC
state: Noord-Holland
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Marcus J Schultz, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Amsterdam UMC, location VUmc
name: Pieter Roel Tuinman, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Frederique Paulus, Dr
role: STUDY_DIRECTOR
affiliation: Amsterdam UMC, location VUmc
name: Leo MA Heunks
role: STUDY_DIRECTOR
References: