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Status unknownNCT03447288BEARDSUpdated Sep 30, 2021

Incidence of Dyssynchronies in Early ARDS

An observational study in ARDS and Acute Hypoxemic Respiratory Failure, sponsored by Unity Health Toronto. Status unknown at 14 sites in 10 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-09-30.

Sponsored by Unity Health Toronto · Observational

The sponsor has not verified this record recently (last verified Sep 2021), so the status shown — last known as Recruiting — may be out of date.
Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
300
Ages
18 Years and older
Sex
All
01

Study summary

Patients sedated under mechanical ventilation with acute hypoxemic respiratory failure with a PaO2/FiO2 equal or less than 200mmHg (Acute Respiratory Distress Syndrome, ARDS and non-ARDS) will be included in the study early in the course of the disease (first week of mechanical ventilation). At enrollment, data on the clinical condition of the patient will be recorded together with ventilation settings: ventilation mode, the fraction of inspired oxygen (FiO2), PEEP, tidal volume, set pressure, respiratory rate, time of the respiratory cycle, recent blood gas parameters.

Airway pressure, flow, and esophageal pressure (or alternatively electrical activity of the diaphragm, Eadi) will be recorded 3 times a day for 7 days:

  1. Period 1 (morning): duration 20-30 minutes
  2. Period 2 (afternoon): duration 20-30 minutes
  3. Period 3 (evening / night): duration 20-30 minutes

Registration will be ended at extubation, death or at eight days from the first recording.

Monitoring of vital parameters (hemodynamic and respiratory) will be continuous throughout the duration of the study, as per normal clinical practice. All drugs used during the day of the measurements will be recorded. The patient will then be followed until discharge from the ICU and after 60 days of discharge to evaluate mortality.

As an ancillary study, in a subgroup of patients continuous simplified measurement of respiratory recordings together with hourly clinical data on sedation and extended simplified polysomnography recordings will be performed within the first 7 days from inclusion.

The analysis of the recorded waveforms will be performed in a single center by a centralized system that will quantify dyssynchrony and its intensity, calculate pressure time product, collect clinical and physiological data and outcome, and investigate possible correlations.

Read the detailed description

Measurements

Physiological measurements Airway pressure, esophageal pressure, electrical activity of the diaphragm and flow

  1. Flow and airway pressure signal will be recorded from the ventilators by connecting the ventilator to a laptop computer if possible. Recording these data simultaneously with esophageal pressure or electrical activity of the diaphragm (see later in protocol for details) could be technically unfeasible. In this case, a flow sensor and an additional port for pressure measurement will be connected to the endotracheal tube proximal to the Y connector (without interfering with patient's breathing). Both, flow sensor and pressure port will be connected to differential pressure transducers respectively. Signals will be acquired with at least 100 Hz sampling.
  2. In centers used to perform esophageal pressure measurements, an esophageal catheter will be inserted as per usual clinical practice, checked for accuracy with an occlusion test, and connected to a 3 ways stopcock and a pressure transducer. The occlusion test will be recorded and performed before any new recordings. Any ventilator can be used if an esophageal pressure is used.
  3. If available, in centers used to record or monitor the electrical activity of the diaphragm, instead of an esophageal catheter, the electrical activity of the diaphragm will be provided by a catheter dedicated to the monitoring of the electrical activity of the diaphragm, or EaDi, on a Servo-I or Servo-U ventilator (Maquet©, Lund, Sweden). This catheter is formally designed to be used for a specific mode of ventilation called Neurally Adjusted Ventilatory Assist (NAVA) but here will be used for monitoring purposes only (NAVA catheter). In such cases a specific software (Servotracker, Maquet) may be used to record all signals from the ventilator.
  4. In case the patient has been enrolled but the esophageal catheter cannot be placed or is contraindicated, the recordings will be limited to airway pressure and flow. Each centre should have a minimum of 5 patients with esophageal catheter or electrical activity recording.
  5. As an ancillary study, in a subgroup of patients, simplified recordings will be obtained only flow and airway pressure signals will be performed continuously directly taken from the ventilator by connecting the ventilator to a laptop computer equipped with a special software for off line analysis (Better Care ©, Sabadell, Spain).
  6. Occlusion pressure (or pressure at 0.1 sec, P0.1) as an index of respiratory drive. In patients triggering the ventilator, the P0.1 will be analyzed from the tracings. The only condition to have reliable measurements is to use a pressure triggering, not a flow triggering.

As an ancillary study, in a subgroup of patients, a simplified extended polysomnography recording will be performed during the first 7 days after inclusion using a home polysomnography device (Prodigy, CerebraHealth ©, Canada) equipped with 2 frontal EEG a reference electrode to the mastoid, EMG, and electrooculogram.

Data collection

At the beginning of the recordings, ventilatory settings will be collected: ventilator brand, mode of ventilation and settings including: FiO2, PEEP, set and real tidal volume (or pressure), set and real respiratory rate, maximum inspiratory flow, inspiratory time, Glasgow coma scale and Richmond Agitation Sedation Scale (RASS) or Riker Sedation Agitation Scale (SAS). Any medications used at the day of the measurement and before will be collected especially neuromuscular blocking agents, sedatives (brands and doses), opiates and vasopressors including dose, duration of the treatment and date of last use. Investigators will also collect clinical characteristics of the patients (SAPS and SOFA at ICU admission and at the day of the recording, main ARDS or AHRF etiology and risk factors, age, gender, weight, height, days of mechanical ventilation, patient's position -supine vs prone-, kidney and liver function). Other comorbidities will be recorded, with special emphasis in the ones that could affect the incidence of the studied phenomenon, such as: COPD, lung transplant or any neuromuscular condition that could affect the respiratory drive or respiratory muscle function.

Patients will be followed up to get the total duration of mechanical ventilation, ICU length of stay, day of the first weaning attempt, day of tracheotomy if any, status at ICU discharge (alive or death) and at hospital discharge and at day 60.

02

Conditions studied

  • ARDS
  • Acute Hypoxemic Respiratory Failure

Keywords

  • Dyssynchrony
  • Breath-stacking
  • Asynchrony
  • Reverse Triggering
  • Mechanical Ventilation
  • Sedation
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Probability sample

Study population

Patients with moderate to severe acute hypoxemic respiratory failure (ARDS and non-ARDS) under sedation and mechanical ventilation.

Inclusion criteria

  • Moderate and severe ARDS and AHRF, according to the Berlin definition. The absence of the Chest X-Ray criterion (e.g. unilateral disease) or the presence of primary cardiac dysfunction will define AHRF.
  • Continuous intravenous sedation
  • Deep sedation: Richmond Agitation Sedation Scale (RASS) ≤ -3 or Riker Sedation-Agitation Scale (SAS) ≤ 3

Exclusion criteria

Exclusion Criteria:

  • \<18 years
  • Patients with a significant bronchopleural fistula
  • Pure COPD exacerbation
  • Patients on chronic home ventilation
04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
300 participants (estimated)
Target follow-up
60 Days
Patient registry
Yes
05

What researchers measure

Primary outcomes

  1. Prevalence of dyssynchrony

    For each patients, the number of dyssynchrony (reverse triggering, breath stacking, short cycles) will be counted over the recorded period. An asynchrony index, (number of dyssynchrony divided by the total number of breaths) as well as the number of dyssynchrony per minute will be calculated globally and for each dyssynchrony type. Patients with ARDS will be compared to patients with AHRF. Patients with severe ARDS or severe AHRF (\<120) will be compared to less severe patients.

    Time frame: Within 1 Year

Secondary outcomes

  1. Intensity of dyssynchrony

    Assessement of the frequency and magnitude of effort assessed by esophageal pressure or electrical activity of he diaphragm for each type of dyssynchrony

    Time frame: Within 1 Year

  2. Correlation of clinical outcome with intensity of dyssynchrony

    Outcomes will be the duration of mechanical ventilation (in days); the number of ventilator-free days at day 28 (number of days alive without mechanical ventilation in 28 days; death equals 0 ventilator-free days); ICU survival and hospital survival. For each type of dyssynchrony, the outcomes will be correlated with the intensity of dyssynchrony. Intensity of dyssynchrony will be based on the dyssynchrony index above a minimal level of effort for each dyssynchrony. The outcomes above several thresholds of dyssynchrony index (10%, 30%, 50%) will be compared.

    Time frame: Within 1 Year

  3. Impact of reverse triggering on breathing effort

    The breathing effort (pressure-time product) will be calculated and its value will be compared for breaths with and without reverse triggering.

    Time frame: Within 1 Year

  4. Quantification of spontaneous breathing efforts associated with dyssynchronies.

    For each dyssynchrony found, the effort measured by the pressure-time product using esophageal pressure will be calculated. And the clinically relevant dyssynchronies will be determined based on a minimal amount of effort.

    Time frame: Within 1 Year

  5. Association between pH and Dyssynchrony

    Arterial pH will be compared at different values of dyssynchrony index above a minimal level (10%, 30% and 50%).

    Time frame: Within 1 Year

  6. Association between sedation and Dyssynchrony

    Level of sedation (assessed either Sedation Agitation Score "SAS" or the Richmond Agitation and Sedation Scale "RASS") by the will be compared at different values of dyssynchrony index above a minimal level (10%, 30% and 50%).

    Time frame: Within 1 Year

  7. Association between sedatives and Dyssynchrony

    Values of dyssynchrony index above a minimal level will be compared between patients receiving primarily propofol versus benzodiazepines.

    Time frame: Within 1 Year

  8. Clusters of dyssynchronies

    Timing of detection of dyssynchrony

    Time frame: Within 1 Year

  9. Sleep depth measured with EEG

    As part of an ancillary exploratory study, various measures of brain activity, using EEG derived parameters including distribution of sleep depth using an automated scoring system named Odds Ratio Product (ORP) will be studied. ORP score ranges from 0 (corresponding to deep sleep) to 2.5 (corresponding to full wakefulness).

    Time frame: Within 1 Year

06

Study locations

10 of 14 sites recruiting
  • St Michael's hospital
    Toronto, Ontario M5B 1W8, Canada
    • Tài Pham, Md, PhD · Contact · phamo@smh.ca · 647-643-2808
    Recruiting
  • Toronto General Hospital
    Toronto, Ontario M5G 2C4, Canada
    Not yet recruiting
  • Beijing Tiantan Hospital, Capital Medical University
    Beijing, 100050, China
    Not yet recruiting
  • Centre Hospitalier Universitaire - CHU Angers
    Angers, 49933, France
    Not yet recruiting
  • Universitätsklinikum Schleswig-Holstein
    Kiel, 24105, Germany
    Recruiting
  • University Hospital of Heraklion
    Heraklion, 711 10, Greece
    Recruiting
  • University of Ferrara
    Ferrara, Italy
    Recruiting
  • Azienda Ospedaliero - Universitaria OORR Ospedali Riuniti di Foggia
    Foggia, 71122, Italy
    Not yet recruiting
  • ASST Santi Paolo e Carlo
    Milano, Italy
    Recruiting
  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
    Milano, Italy
    Recruiting
  • VU University Medical Centre Amsterdam
    Amsterdam, 1007 MB, Netherlands
    Recruiting
  • Vall d'Hebron University Hospital
    Barcelona, Spain
    Recruiting
  • National Cheng-Kung University and Hospital
    Tainan City, 704, Taiwan
    Recruiting
  • Siriraj Hospital
    Bangkok, 10700, Thailand
    Recruiting
07

References and documents

Publications

  • Bianchi I, Grassi A, Pham T, Telias I, Teggia Droghi M, Vieira F, Jonkman A, Brochard L, Bellani G. Reliability of plateau pressure during patient-triggered assisted ventilation. Analysis of a multicentre database. J Crit Care. 2022 Apr;68:96-103. doi: 10.1016/j.jcrc.2021.12.002. Epub 2021 Dec 21. Erratum In: J Crit Care. 2022 Dec;72:154030. doi: 10.1016/j.jcrc.2022.154030. PubMed 34952477 ↗
  • Pham T, Montanya J, Telias I, Piraino T, Magrans R, Coudroy R, Damiani LF, Mellado Artigas R, Madorno M, Blanch L, Brochard L; BEARDS study investigators. Automated detection and quantification of reverse triggering effort under mechanical ventilation. Crit Care. 2021 Feb 15;25(1):60. doi: 10.1186/s13054-020-03387-3. PubMed 33588912 ↗

Individual participant data

Plan to share: Undecided — We plan to share physiologic tracings with no participant identification.

08

Registry details

Key details

Study ID
NCT03447288
Lead sponsor
Unity Health Toronto
Responsible party
Sponsor
First posted
Feb 27, 2018
Start date
Jan 15, 2017
Primary completion
Aug 2022 (estimated)
Completion
Aug 2022 (estimated)
Last update
Sep 30, 2021

Study contacts

Laurent Brochard, Dr.
Contact
BrochardL@smh.ca
416-864-6060 ext. 5686
Tài Pham, Dr.
Contact
phamo@smh.ca
647-643-29808
Laurent Brochard, Dr.
principal investigator · Unity Health Toronto

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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This study is status unknown, as verified in Sep 2021. You cannot join it, but the record below documents what was studied.

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