Clinical trial NCT02731898: Fourth International Study of Mechanical Ventilation From VENTILA GROUP
Official title: Fourth International Study of Mechanical Ventilation From VENTILA GROUP
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Respiratory Failure, Mechanical Ventilation, Critically Ill Patients, Mortality
Lead sponsor: Hospital Universitario Getafe
Sponsor class: OTHER
First posted: 2016-04-08
Enrollment: 3000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: In order to include patients from different countries and being comparable between them, the coordinator team will create some definitions for the selection of the participating ICUs from each country and inclusion criteria for the patients, as following.

This study will be conducted in Intensive Care Units (\[Medical ICU, MICU\], Coronary ICU \[CCU\], Surgical ICU \[SICU\], neurocritical ICU) that meet the following criteria:

1. ICUs that have six or more beds and/or average (during prior 12 months) of more than 30% of the patients admitted requiring mechanical ventilation.
2. ICUs that have staff specialists in Intensive Care Medicine, or visiting physicians with intensive care training and/or physicians who have more than five years of intensive care experience.

Brief summary: A prospective, international and multicenter, non interventional single-cohort study, which will enroll consecutive adult patients who have received mechanical ventilation (invasive and noninvasive ventilation) for at least 12 hours during a 1-month period, and will follow each patient for the duration of mechanical ventilation, up to 28 days. The main objectives will be to analyze the mortality and clinical outcomes in ventilated patients and secondly, to evaluate the practices of liberation from mechanical ventilation, the failure of non invasive ventilation in the ICU, and to analyze the clinical outcomes in specific populations of critically ill patients with the need of mechanical ventilation.

Detailed description: Mechanical ventilation is commonly used in patients admitted to intensive care units (ICUs). Clinical studies have investigated some of the aspects associated with its utilization, and have contributed to improve the knowledge and management of patients with acute respiratory failure. In 1998, the main researchers conducted the first international study on mechanical ventilation, including 5183 patients who were mechanically ventilated longer than 12 hours. Six years later, the investigators carried out the second international study on mechanical ventilation including 4968 patients. These studies allowed to analyze the evolution of mechanical ventilation and to judge the concordance of practice with results of randomized trials. The main finding of this study was the high degree of concordance between observed changes in mechanical ventilation practice and changes predicted from reports of randomized controlled trials. However, despite apparently beneficial changes in ventilatory practice, the results did not able to detect significant differences in clinical outcomes over this time period. These results have served as an updated benchmark on the usual care and outcomes of mechanically ventilaed patients in a 'real-world' setting. Lastly, in 2010 the main researchers finished the Third International Study of Mechanical Ventilation and were able to find out, for the first time, a significant reduction of ICU mortality in mechanically ventilated patients. Then, the investigators propose to lead up the fourth-international study of mechanical ventilation. This study will keep the same methodology and it will be a prospective, international and multicenter non interventional single-cohort study, which will enroll consecutive patients who have received mechanical ventilation (invasive and noninvasive ventilation) for at least 12 hours during a 1-month period, and will follow each patient for the duration of mechanical ventilation, up to 28 days. Despite of all the current implementations in different ventilatory strategies, and new ventilatory modalities, the mortality and clinical outcomes in critically ill patients under mechanical ventilation is poorly known all over the world. The aims of this study are:

1. To evaluate the impact and clinical outcomes in ventilated patients over the world; and to determine the factors associated with the clinical outcomes in ventilated critically ill patients
2. To analyze the aspects related with the process of liberation from mechanical ventilation;
3. To determine the clinical outcomes of patients with failure of noninvasive ventilation (NIV) in the ICU;
4. To evaluate what differences may occur between geographical areas in the ventilatory management of mechanically ventilated patients.
5. To describe the clinical outcomes in specific populations of critically ill patients with the need of mechanical ventilation:

5.a: Outcomes of prolonged mechanically ventilated patients. 5.b: Prevalence of delirium in mechanically ventilated patients. 5.c: Performance of tracheostomy and outcomes of tracheostomized patients. 5.d: Outcomes of mechanically ventilated patients due to neurologic diseases. 5.f: Outcomes of mechanically ventilated patients due to chronic obstructive pulmonary disease.

5.g: Outcomes of mechanically ventilated patients due to acute renal failure. 5.h: Outcomes of mechanically ventilated patients due to hypercapnia in patients with acute respiratory distress syndrome (ARDS).

5.i: Prediction and Prevalence of ICU acquired weakness (ICUAW) in mechanically ventilated patients.

5.j: Clinical Outcomes and associated factors with reintubation in ventilated patients.

5.k: Clinical Outcomes of elderly patients subjected to mechanical ventilation. 5.l: Clinical impact of the use of sedatives and analgesic drugs in mechanically ventilated patients.

Design of the study This is a multicenter, international, observational and non-interventional study that will collect data of all patients who are admitted to the study ICUs and who meet the inclusion/exclusion criteria between May 1st, 2016 at 00:00 hours and May 31st, 2016 at 23:59 hours. Patients who were already mechanically ventilated prior to April 1 at 00:00 hours will not be included in the study. Approval from the research ethics board of each participating institutions will be sought for this protocol. Only the investigator and research coordinators at each site should be aware of the purpose and the precise timing of the study, in order to minimize any practice modification in response to clinicians' knowledge that they are under observation.

Main variables

For the main purpose of the study we will consider the following variables to fill out:

• Date of ICU admission, mode of mechanical ventilation, date of initiation of mechanical ventilation, demographic dates (age, gender, reason to start mechanical ventilation, severity score at admission, weight, and height), arterial blood gas at the beginning of mechanical ventilation, daily ventilator parameters (applied positive end expiratory pressure \[PEEP\], volume tidal, peak pressure, plateau pressure), mode of NIV, duration of NIV (failure and success), monitoring during NIV (respiratory rate, sedation scale \[Richmond Agitation Sedation Scale, RASS\], arterial blood gas during NIV \[at the beginning, every 2 hours of NIV if tolerated, and if it failed\]), date of the starting of withdrawal of mechanical ventilation, method for weaning in the first attempt, mode of spontaneous breathing trial (SBT), reason for failure of SBT, date of extubation, date of reintubation, arterial blood gas at the time for extubation, reason for reintubation, development of complications during mechanical ventilation (organ failures \[cardiovascular, hematological, hepatic or renal failures\], barotrauma, ARDS, sepsis, ventilator-associated pneumonia, ICUAW), tracheostomy if needed, date of tracheostomy, type of tracheostomy, date of ICU discharge and status of ICU discharge, reason of ICU mortality, status at hospital discharge, length of ICU and hospital stays.

7. Secondary variables

We consider secondary parameter the following:

• Mode of mechanical ventilation, brand of the ventilator, biochemical parameters during mechanical ventilation, use of co-adjuvant therapies (corticosteroids, insulin therapy), use of medications (neuromuscular blockers, sedatives and analgesics), type of interfaces for NIV, type of respirator for NIV, fluid balance, NIV at home, previous tracheostomy, any isolated ventilator monitoring and setting during mechanical ventilation (invasive or not invasive ventilation), destination after hospital discharge.

STATISTICAL ANALYSIS Randomization This is a prospective, observational, and no intervention study, and therefore, randomization is not applicable.

Sample size calculation Despite of the characteristics of this observational study (an international survey) with multiple objectives to evaluate, we decided to include patients according with the calculation of the sample size for the main objective (ICU mortality). In this way, we estimated that 2,600 patients would need to be enrolled for the study to have 90% power to detect a rate of survival to ICU discharge of 23% versus 28% in the previous study, at an overall two-sided alpha level of 0.05, and assuming 20% of missing patients. The secondary ob-jectives will be tested using the same sample size.

Statistical Methods Appropriate statistical analyses will be conducted. Data will be express as mean (standard deviation), median (interquartile range) and proportion as appropriate. Student's t or Mann Whitney U tests will be use to compare continuous variables and chi-squared tests were used for categorical variables. Statistical analyses will be conducted using appropri-ate statistical software according to evaluated outcome.

Quality Control Extensive efforts will be made to ensure the quality of the data collected throughout the study. At each site, the study physicians, including review of the chart, will review the data from a randomly chosen 5 percent of screened patients and from all patients about whom the screeners had questions. Data from a random sample of 7 percent of cases were abstracted and entered into the database twice, with an error rate of less than 0.25 percent. The charts were reevaluated until the final notes, laboratory test results, and oth-er results will be completed. Complete data will be necessary to include patients in the final analysis, and we will accept patients with no missing data for the main variables or patients with missing data less than 10% for secondary variables.

Ethical and legal issues in this study. Patterns of practices in different hospitals are often idiosyncratic and empiric based in usual care of mechanically ventilated patients.

The study design will provide high quality information about the ventilatory management of critically ill patients from a very large cohort of subjects in a short period of time. It will inform clinical practice much more rapidly than would be possible with a standard randomized clinical trials. Given the study design and the use of anonymous surveys based in routine clinical parameters and ventilatory setting from critically ill patients, the main coordinator team guarantees the ano-nymity of the patients included in the study.

There is no possibility for reporting any adverse events due the type of study (international, pro-spective and non-interventional survey).

Therefore, given the low risk nature of the research (nonintervention study), the anonymity of the survey, and the "unreasonable effort" to get the written informed consent, we will use a pro-cess of "opt-out consent" which involves the provision of information to patients (Information Form) and their next kin and the opportunity to opt-out from the use of their data if they wish.

Confidentiality of patient data Patients will be allocated a unique study code. The site research coordinator will enroll the patient in the international database and the main coordinator of the study will create an enrollment number that include the country, the unit and the unique study code. Study data will be obtained from routinely collected quality assurance. The unique number will identify data entered into the study database only that guarantee the irreversibility of clinical data.

DATA MANAGEMENT Data collection methods All data used in this study are routinely collected from the clinical parameters obtained daily during the ICU admission. These data will be collected by each participating center led by a local coordinator and saved in an online database. This database will be design in the Hospital Universitario de Getafe.

Data monitoring Committee (DMC) A committee of three main investigators (Fernando Frutos Vivar, Óscar Penuelas, Alfonso Muriel) will ensure the rights and safety of patients involved in the study are protected.

FUNDING This study, including the protocol, will be upload in clinicaltrials.com and supported by the Centro de Investigaciones Biomédicas en Red; (CIBER of Respiratory Diseases (CIBER de Enfermedades Respiratorias del Instituto Carlos III) and the Respiratory Group from the Spanish Society of Intensive Care Medicine (Grupo de Respiratorio de la Sociedad Española de Cuidados Intensivos y Unidades Coronarias, SEMICYUC).

This study will not have any financial support. The main researchers of the study does not conflicts of interest to disclosure.

Eligibility criteria: Inclusion Criteria:

1. Patients who are admitted to the ICU and will require invasive mechanical ventilation (endotracheal tube or tracheostomy) longer than 12 hours.
2. Patients who are admitted to the ICU and will require NIV (Continuos Positive Airway Pressure \[CPAP\], or refers to Bilevel Positive Airway Pressure \[BIPAP\] with oronasal, nasal, helmet or facial mask) for more than 1 hour.
3. Patients in whom mechanical ventilation was started outside the study ICU at the same Institution and/or a different Institution, including Emergency Room, Operating Room (OR), and were then transferred to the ICU at the participating center.

Exclusion Criteria:

1. Pediatric ICU.
2. Post-Operators Anesthesia Recovery Room.
3. Patients less than 18 years old will be also excluded.
4. Patients admitted after elective surgery and who require mechanical ventilation for less than 12 hours (excepting patients who receive NIV).

Primary outcomes:
measure: ICU Mortality,
timeFrame: one month
Secondary outcomes:
measure: duration of mechanical ventilation
timeFrame: one month
measure: duration of period of liberation from mechanical ventilation
timeFrame: one month
measure: extubation failure
timeFrame: one month
measure: reintubation rate
timeFrame: one month
measure: tracheostomy rate
timeFrame: one month
measure: 28-day mortality
timeFrame: one month
measure: hospital mortality
timeFrame: one month
measure: failure of noninvasive ventilation
timeFrame: one month
measure: lenght of ICU stay
timeFrame: one month
measure: lenght of hospital stay
timeFrame: one month
Other outcomes:
Locations:
city: Getafe
country: Spain
facility: Intensive Care Unit, Hospital Universitario de Getafe
state: Madrid
city: Barakaldo
country: Spain
facility: Hospital de Cruces
state: Vizcaya
city: A Coruna
country: Spain
facility: Complejo Hospitalario Universitario de A Coruna
Study officials:
affiliation: Hospital Universitario de Getafe, Madrid, Spain
name: Oscar Penuelas, M.D.
role: PRINCIPAL_INVESTIGATOR
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