Lung Ultrasound-Guided Fluid Deresuscitation in ICU Patients

Mechanical Ventilation Clinical Trial

— CONFIDENCE  

Official title:

Effect of Lung Ultrasound-Guided Fluid Deresuscitation on Duration of Ventilation in Intensive Care Unit Patients (CONFIDENCE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05188092
• Other study ID #: CONFIDENCE
• Status: Recruiting
• Phase: N/A
• Start date: December 22, 2021
• Est. completion date: December 1, 2025

Study information

• Verified date: December 2022
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: Amne Mousa, MSc
• Phone: 06 500 876 37
• Email: a.mousa1[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 a national 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).

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 the Netherlands. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 1, 2025
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Fluid Overload
• Mechanical Ventilation
• Ventilator-free Days

Intervention

Other:
• Lung ultrasound guided deresuscitation
With every new LUS examination, the following scenarios, with distinct recommendations, are possible: LUS observations suggest massive pulmonary fluid overload, with the recommendation to minimize fluid infusion and start fluid withdrawal, targeting a negative fluid balance of at least -1500 ml in the next 24 hours; LUS suggests some pulmonary edema and/or significant pleural effusion. These LUS observations suggest little pulmonary fluid overload, with the suggestion to minimize fluid infusion and start fluid withdrawal, targeting a negative fluid balance at least -500 ml in the next 24 hours; LUS suggests absence of pulmonary edema and no pleural effusion. These LUS observations suggest no fluid overload, with the suggestion to target a neutral fluid balance in the next 24 hours.

Locations

Country	Name	City	State
Netherlands	Amsterdam UMC, location AMC	Amsterdam	Noord Holland
Netherlands	Amsterdam UMC, location VUMC	Amsterdam	Noord-Holland
Netherlands	Rijnstate	Arnhem	Gelderland

Sponsors (2)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ventilator free days(VFD) and alive at day 28	Patient is alive and breathes without assistance of the mechanical ventilator, if the period of unassisted breathing lasted at least 24 consecutive hours: VFD-28 = 0 if subject dies within 28 days of mechanical ventilation; VFD-28 = 28 - x if successfully liberated from ventilation x days after initiation Succcessful liberation: extubation (planned or unplanned) without death or reintubation within the next 72 hours; VFD-28 = 0 if the subject is mechanically ventilated for = 28 days	28 days after randomisation
Secondary	Duration of ventilation	Duration of ventilation in survivors	28 days
Secondary	ICU length of stay	Length of stay in the intensive care unit	28 days
Secondary	Hospital length of stay	Length of stay in the hospital	28 days
Secondary	28 day mortality	Mortality after 28 days	28 days
Secondary	90 day mortality	Mortality after 90 days	90 days
Secondary	Incidences of reintubations	Need of reintubation within 72 hours after extubation	28 days
Secondary	Cumulative fluid balances after randomization	Cumulative fluid balance on day 1-7 after randomization;	7 days
Secondary	Cumulative fluid balances after start of lung ultrasound examination	Cumulative fluid balance on day 1-7 after start of lung ultrasound examinations;	7 days
Secondary	Incidence of acute kidney injury	Kidney injury with Kidney Disease Improving Global Outcomes (KDIGO) stadium = 2	28 days