Acute Respiratory Failure, Mechanical Ventilation, Critically Ill Patients, Mortality Clinical Trial
Official title:
Fourth International Study of Mechanical Ventilation From VENTILA GROUP
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.
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.
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