Clinical trial NCT01868321: Practice of Ventilation in Critically Ill Patients Without ARDS
Official title: Practice of Ventilation in Critically Ill Patients Without Acute Respiratory Distress Syndrome - An International Observational Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Mechanical Ventilation
Keywords: Mechanical ventilation
Acute respiratory failure
Acute respiratory distress syndrome
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: European Society of Anaesthesiology
First posted: 2013-06-04
Enrollment: 1030
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Intubated and ventilated ICU-patients.

Brief summary: The purpose of this international, multicenter study is to determine ventilation practice and outcomes of intubated and ventilated intensive care unit (ICU) patients. Ventilation characteristics and outcomes will be compared between patients without the acute respiratory distress syndrome (ARDS), patients at risk for ARDS, and patients with mild, moderate or severe ARDS.

Participating centres worldwide will include adult patients undergoing mechanical ventilation in the ICU during a 7-day period. Patients data will be collected during the first 7 days in the ICU, or until ICU discharge. Follow up is until day 90. Primary endpoint is the tidal volume size used during mechanical ventilation. Secondary endpoints are development of ARDS in patients without ARDS at the onset of mechanical ventilation, worsening of ARDS in patients with ARDS at the onset of mechanical ventilation, pulmonary infection, other pulmonary complications, need for tracheostomy, extra-pulmonary complications, duration of ventilation, length of ICU and hospital stay, and ICU, hospital and 90-day mortality.

Detailed description: Research questions:

1. Does ventilation practice, in particular tidal volume size, varies amongst patients without ARDS, patients at risk for ARDS, and patients with mild ARDS?
2. Are tidal volumes used in patients without ARDS higher than those used in patients with ARDS?
3. Are the outcomes in patients without ARDS dependent on the size of tidal volumes?

   * Methods: In this international observational study, consecutive patients in the ICU under mechanical ventilation are eligible for participation. Patients in participating centers will be screened on a daily basis. Patients in mechanical ventilation will be included during a 7-day period, from Monday at 8:00 AM to the next Monday at 7:59 AM (in time zones of the participating centers). The inclusion period will be flexible for participating centers and determined at a later stage together with the study-coordinator.

Times points of data collection:

1. Demographic data and baseline data, including severity scores (e.g. APACHE II-scores and SAPS III) and LIPS, are collected from the clinical files on the day of intubation
2. Ventilation settings, gas exchange variables and vital parameters are collected once a daily in the morning, until ventilation is stopped
3. Chest radiography data from available chest X-rays (i.e., no extra chest X-rays are obtained)
4. Predefined complications are recorded from medical chart until discharge from ICU or death, whatever comes first
5. Length of ICU and hospital stay, and ICU, hospital and 90-day mortality

   * Centres: The investigators aim to recruit 40 - 150 centers worldwide.
   * Ethics Approval: National coordinators will be responsible for clarifying the need for ethics approval and applying for this where appropriate according to local policy. Centres will not be permitted to record data unless ethics approval or an equivalent waiver is in place. The investigators expect that in most, if not every participating country, a patient informed consent is not be required.
   * Monitoring: Due to the observational nature of the study, a DSMB is not be necessary.
   * Study Population: Adult patients in the ICU under mechanical ventilation.
   * Data Collection: Data will be collected at inclusion, every day during seven days, day of ICU and hospital discharge and on day 90. Data will be coded by a patient identification number (PIN) of which the code will be kept safe at the local sites. The data will be transcribed by local investigators onto an internet based electronic CRF.
   * Sample Size Calculation: We did not perform a formal sample size calculation, seen the largely descriptive character of this investigation. We expect to collect data from at least 1000 patients, which will be sufficient to test the hypotheses.
   * Statistical Analysis: Patient characteristics will be compared and described by appropriate statistics. Student's t-test or Mann-Whitney U-tests are used to compare continuous variables and chi-squared tests are used for categorical variables. Data are expressed as means (SD), medians (interquartile range) and proportions as appropriate. Comparisons between and within groups are performed using one-way ANOVA and post-hoc analyses for continuous variables.

The primary analysis concerns the determination of (variation of) tidal volume size in patients without ARDS. Tidal volume size is compared between predefined patient groups: patients at no risk for ARDS, patients at risk for ARDS, patients with mild ARDS, and patients with moderate or severe ARDS.

To identify potential factors associated with outcome like development of ARDS, or worsening of ARDS, development of pulmonary complications, duration of ventilation, or death, univariate analyses are performed. A multivariate logistic regression model is used to identify independent risk factors. A stepwise approach is used to enter new terms into the model, with a limit of p \< 0.2 to enter the terms. Time to event variables are analyzed using Cox regression and visualized by Kaplan-Meier.

- Organization: The study is conducted by the PROtective VEntilation Network (PROVENet). National co-ordinators will lead the project within individual nations and identify participating hospitals, translate study paperwork, distribute study paperwork and ensure necessary regulatory approvals are in place. They provide assistance to the participating clinical sites in trial management, record keeping and data management. Local coordinators in each site will supervise data collection and ensure adherence to Good Clinical Practice during the trial.

Eligibility criteria: Inclusion Criteria:

* Admitted to a participating ICU
* Intubated in the participating ICU, or in the emergency room or operation room before the present ICU admission

Exclusion Criteria:

* Age \< 18 years
* Receiving only non-invasive ventilation
* Patients under invasive mechanical ventilation previous to the 7-day period of inclusion
* Patients transferred from another hospital under invasive mechanical ventilation

Primary outcomes:
measure: Tidal Volume Size
timeFrame: During mechanical ventilation
Secondary outcomes:
measure: Other Ventilation Parameters
timeFrame: During mechanical ventilation
measure: Development of ARDS
timeFrame: From date of inclusion until the date of first documented ARDS or date of hospital discharge or death from any cause, whichever came first, assessed up to three months
measure: Worsening of ARDS
timeFrame: From date of inclusion until the date of first documented worsening of ARDS or date of hospital discharge or death from any cause, whichever came first, assessed up to three months
measure: Other Pulmonary Complications
timeFrame: From date of inclusion until the date of first documented pulmonary complication or date of hospital discharge or death from any cause, whichever came first, assessed up to three months
measure: Pulmonary Infection
timeFrame: From date of inclusion until the date of first documented pulmonary infection or date of hospital discharge or death from any cause, whichever came first, assessed up to three months
measure: Need for Tracheostomy
timeFrame: From date of inclusion until the date of first documented tracheostomy or date of hospital discharge or death from any cause, whichever came first, assessed up to three months
measure: Extra-Pulmonary Complications
timeFrame: From date of inclusion until the date of first documented extra-pulmonary complication or date of hospital discharge or death from any cause, whichever came first, assessed up to three months
measure: Duration of Mechanical Ventilation
timeFrame: During mechanical ventilation
measure: Length of Stay in ICU on Day 90
timeFrame: Until day 90
measure: Length of Stay in Hospital on Day 90
timeFrame: Until day 90
measure: All-cause ICU Mortality
timeFrame: Until day 90
measure: All-cause Hospital Mortality
timeFrame: Until day 90
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University Viena
city: Leuven
country: Belgium
facility: University Hospital Leuven
city: São Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
state: SP
city: Santo André
country: Brazil
facility: Faculdade de Medicina do ABC
state: São Paulo
city: Santiago
country: Chile
facility: Hospital Clínico de la Pontificia Universidad Católica de Chile
city: Montpellier
country: France
facility: Saint Eloi University Hospital
city: Bonn
country: Germany
facility: University Hospital Bonn
city: Dresden
country: Germany
facility: University Clinic Carl Gustav Carus
city: Leipzig
country: Germany
facility: University of Leipzig
city: Genoa
country: Italy
facility: University of Genoa
city: Varese
country: Italy
facility: University of Insubria
city: Amsterdam
country: Netherlands
facility: Academic Medical Centre
city: Barcelona
country: Spain
facility: Hospital Universitari Germans Trias I Pujol
Study officials:
affiliation: Department of Intensive Care, Academic Medical Center, University of Amsterdam
name: Marcus J Schultz, MD, PhD
role: STUDY_CHAIR
affiliation: PRoVENT Study Trial Coordinator, Department of Intensive Care, Academic Medical Center, University of Amsterdam
name: Ary Serpa Neto, MD, MSc
role: STUDY_DIRECTOR
affiliation: Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Italy
name: Paolo Pelosi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Germany
name: Marcelo Gama de Abreu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Intensive Care, Hospital Israelita Albert Einstein
name: Carmen SV Barbas, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hemmes SN, Serpa Neto A, Schultz MJ. Intraoperative ventilatory strategies to prevent postoperative pulmonary complications: a meta-analysis. Curr Opin Anaesthesiol. 2013 Apr;26(2):126-33. doi: 10.1097/ACO.0b013e32835e1242.
citation: Serpa Neto A, Cardoso SO, Manetta JA, Pereira VG, Esposito DC, Pasqualucci Mde O, Damasceno MC, Schultz MJ. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA. 2012 Oct 24;308(16):1651-9. doi: 10.1001/jama.2012.13730.
citation: Determann RM, Royakkers A, Wolthuis EK, Vlaar AP, Choi G, Paulus F, Hofstra JJ, de Graaff MJ, Korevaar JC, Schultz MJ. Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial. Crit Care. 2010;14(1):R1. doi: 10.1186/cc8230. Epub 2010 Jan 7.
citation: Severgnini P, Selmo G, Lanza C, Chiesa A, Frigerio A, Bacuzzi A, Dionigi G, Novario R, Gregoretti C, de Abreu MG, Schultz MJ, Jaber S, Futier E, Chiaranda M, Pelosi P. Protective mechanical ventilation during general anesthesia for open abdominal surgery improves postoperative pulmonary function. Anesthesiology. 2013 Jun;118(6):1307-21. doi: 10.1097/ALN.0b013e31829102de.
citation: Serpa Neto A, Barbas CSV, Artigas A, et al. Rationale and Study Design of Provent-An International Multicenter Observational Study on Practice of Ventilation in Critically Ill Patients without ARDS. J Clin Trials 2013;3;[in press]
citation: Simonis FD, Barbas CSV, Artigas-Raventos A, Canet J, Determann RM, Anstey J, Hedenstierna G, Hemmes SNT, Hermans G, Hiesmayr M, Hollmann MW, Jaber S, Martin-Loeches I, Mills GH, Pearse RM, Putensen C, Schmid W, Severgnini P, Smith R, Treschan TA, Tschernko EM, Vidal Melo MF, Wrigge H, de Abreu MG, Pelosi P, Schultz MJ, Neto AS; PRoVENT investigators; PROVE Network investigators. Potentially modifiable respiratory variables contributing to outcome in ICU patients without ARDS: a secondary analysis of PRoVENT. Ann Intensive Care. 2018 Mar 21;8(1):39. doi: 10.1186/s13613-018-0385-7.
citation: Neto AS, Barbas CSV, Simonis FD, Artigas-Raventos A, Canet J, Determann RM, Anstey J, Hedenstierna G, Hemmes SNT, Hermans G, Hiesmayr M, Hollmann MW, Jaber S, Martin-Loeches I, Mills GH, Pearse RM, Putensen C, Schmid W, Severgnini P, Smith R, Treschan TA, Tschernko EM, Melo MFV, Wrigge H, de Abreu MG, Pelosi P, Schultz MJ; PRoVENT; PROVE Network investigators. Epidemiological characteristics, practice of ventilation, and clinical outcome in patients at risk of acute respiratory distress syndrome in intensive care units from 16 countries (PRoVENT): an international, multicentre, prospective study. Lancet Respir Med. 2016 Nov;4(11):882-893. doi: 10.1016/S2213-2600(16)30305-8. Epub 2016 Oct 4.