Practice of Ventilation in Critically Ill Patients Without ARDS

Mechanical Ventilation Clinical Trial

— PRoVENT  

Official title:

Practice of Ventilation in Critically Ill Patients Without Acute Respiratory Distress Syndrome - An International Observational Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01868321
• Other study ID #: PRoVENT
• Status: Completed
• Phase: N/A
• First received: May 28, 2013
• Last updated: April 25, 2015
• Start date: April 2014
• Est. completion date: March 2015

Study information

• Verified date: April 2015
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1030
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Acute Lung Injury
• Critical Illness
• Mechanical Ventilation
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn

Locations

Country	Name	City	State
Austria	Medical University Viena	Vienna
Belgium	University Hospital Leuven	Leuven
Brazil	Faculdade de Medicina do ABC	Santo André	São Paulo
Brazil	Hospital Israelita Albert Einstein	São Paulo	SP
Chile	Hospital Clínico de la Pontificia Universidad Católica de Chile	Santiago
France	Saint Eloi University Hospital	Montpellier
Germany	University Hospital Bonn	Bonn
Germany	University Clinic Carl Gustav Carus	Dresden
Germany	University of Leipzig	Leipzig
Italy	University of Genoa	Genoa
Italy	University of Insubria	Varese
Netherlands	Academic Medical Centre	Amsterdam
Spain	Hospital Universitari Germans Trias I Pujol	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Prof. Dr. Marcus J. Schultz	European Society of Anaesthesiology

Countries where clinical trial is conducted

Austria,  Belgium,  Brazil,  Chile,  France,  Germany,  Italy,  Netherlands,  Spain, 

References & Publications (5)

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. — View 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. — View 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]

Serpa Neto A, Cardoso SO, Manetta JA, Pereira VG, Espósito 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tidal Volume Size	Tidal volume size in milliliters per kilogram of predicted body weight	During mechanical ventilation	No
Secondary	Other Ventilation Parameters	Plateau and peak pressure, positive end-expiratory pressure, driving pressure, respiratory rate, inspired oxygen fraction, inspiration to expiration ratio, and minute volume	During mechanical ventilation	No
Secondary	Development of ARDS	Patients are defined as having ARDS if they met the Berlin criteria for ARDS.	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	Yes
Secondary	Worsening of ARDS	Defined as any worse in the degree of severity according to Berlin criteria.	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	Yes
Secondary	Other Pulmonary Complications	Atelectasis, barotrauma, pleural effusion	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	Yes
Secondary	Pulmonary Infection	Defined as need of new antibiotics plus at least one of the following criteria: 1) new or changed sputum; 2) new or changed lung opacities on chest X-ray; 3) temperature > 38.3 ºC; or 4) WBC count > 12,000.	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	Yes
Secondary	Need for Tracheostomy	Need for tracheostomy during hospital stay	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	No
Secondary	Extra-Pulmonary Complications	Acute kidney injury, circulatory failure, gastrointestinal failure, acute or exacerbation of chronic heart failure, liver failure, and delirium.	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	Yes
Secondary	Duration of Mechanical Ventilation	Time between orotracheal intubation and successful extubation; note: in case of intermittent MV via a tracheostomy, every day a patient needs MV counts as one extra day of MV, irrespective of duration of MV that specific day; in case of non-invasive MV, every day a patient needs non-invasive MV counts as one extra day of MV, irrespective of duration of non-invasive MV that specific day.	During mechanical ventilation	No
Secondary	Length of Stay in ICU on Day 90	Time between admission and discharge or death	Until day 90	No
Secondary	Length of Stay in Hospital on Day 90	Time between admission and discharge or death	Until day 90	No
Secondary	All-cause ICU Mortality	Any death during ICU stay	Until day 90	Yes
Secondary	All-cause Hospital Mortality	Any death during hospital stay	Until day 90	Yes

External Links

•   PRotective VENTilation Network
•   PRoVENT website