REVA

Lead investigator:
Coordinating investigator: Jean-Christophe M Richard, réanimation médicale, CHU Rouen.- Alain Mercat, Medical Critical Care, CHU Angers.

Associate investigators :

Justification of the study :
Medical care of acute respiratory distress syndrome (ARDS) has been greatly improved thanks to what has been learnt through experimental and physiological research work followed by a series of controled randomised trials. Yet mortality caused by this syndrome has remained high. Many experimental and clinical projects have shown that a ventilatory mode allowing, from the acute phase, the patient to carry out extra spontaneous ventilation over and above that provided by the respirator (BIPAP-APRV mode) would allow an improvement in gaseous exchanges and hemodynamic tolerance of the ventilation whilst reducing the needs for sedative drugs. Furthermore, this ventilatory mode could minimize the risk of diaphragmatic dysfunction induced by ventilation. Therefore, our assumption is that this ventilation mode could reduce in reducing mortality.
The volume and type of solution used in the vascular filling can also impact on how patients suffering from a severe acute pulmonary inflammatory lesion might evolve (acute respiratory distress syndrome, ARDS). Indication of vascular filling is very frequent in this population given the associated hemodynamic disorders. Restricting volume of fluids enables to reduce the dependency on artificial ventilation. Hypertonic crystalloids have a strong capacity of expansion that could allow to impact more quickly on hemodynamic disorders for a lesser volume administered. Experimental work has also highlighted a reduction of the pulmonary inflammation linked to the use of hypertonic solutions. Our assumption is that a filling with hypertonic crystalloid solutions could reduce ARDS patients mortality.

Ventilation strategy :
The aim of this multicentric , prospective, randomized study is to compare the effects of ventilation strategies on patients suffering from ARDS' mortality and put on mechanical ventilation. A similar current volume (6 ml/kg of predicted weight) and a similar expiratory pressure (set to obtain an tele-inspiratory pressure between 28 et 30 cmH2O) will be used in both strategies. Similarly, oxygenation targets (88 % ≤ SpO2 ≤ 95 % et 55 mmHg ≤ PaO2 ≤ 80 mmHg) and alveloar ventilation (PaCO2 such as 7.30 < arterial pH < 7.45) will be common to both strategies. The BIPAP-APRV strategy will be defined to obtain a spontaneous ventilation corresponding to about 30% of the total ventilation. This will be compared to conventional strategy usually recommended: self-assisted bentilation - controled (VAC). Precise posologic adaptation and weaning rules of sedatives will be used. Similarly, a systematic assessment of the possibility of separating the patient will meet pre-established rules. The main determination parameter will be the hospital mortality.

Filling strategy :
This is a randomized prospective study with double blind test that compares the vascular filling with isotonic crystalloid at 0,9% or hypertonic crystalloid c 3%. The vascular filling will be indicated by clinicobiological criteria in both arms. This will be done by administering a volume of 250ml over a period of 10 min to be renewed until identical predefined hemodynamic objectives are achieved in both arms. Specific rules of adapting vasopressive drugs will be implemented.

Inclusions and duration :
A randomization according to a 2x2 factor plan without interacting with tested treatments will be carried out so as to determine the crystalloid to be administered (iso or hypertonic ; FLU study), the ventilation mode (assistance to spontaneous ventilation by BIPAP-APRV or without spontaneous ventilation by VAC: BIRD study). The key criterion of assessment will be that of hospital mortality. Seven hundred sick patients will be included so as to demonstrate with a 5% alpha risk and an 80 % power, a reduction in mortality by 10 % (25 % vs 35 %). Thirty critical care units will participate in the study over 3 years.

Study title
EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO) FOR SEVERE ACUTE RESPIRATORY DISTRESS SYNDROME (SARS).

Lead investigator:
:Pr Alain COMBES - Medical Critical Care Department, Institut de Cardiologie, Groupe Hospitalier Pitié–Salpêtrière.

Study duration : 30 months.

Study Abstract:
The acute respiratory distress syndrome (ARDS) is a generally severe pulmonary disease whose mortality still remains high. The most severe forms of the disease present an even grimer prognosis with mortality rates exceeding 60%, despite the support of exceptional adjunctive therapeutics. In these circumstances, some teams are putting forward an implementation of an extracorporeal circuit associating a centrifugal pump with a membrane oxygenator hence providing a total pulmonary assistance (oxygenation and purification of the blood CO2), also known as ECMO - ExtraCorporeal Membrane Oxygenation. The ECMO purpose is then to minimize the trauma induced by mechanical ventilation and to provide some rest to the lung. Over the past few years, significant advances have been achieved in the design and production of ECMO circuits, making them more "biocompatible", effective and resistant. The aim of this randomized, multicentric, open and controled study is to assess an early respiratory assistance by early veno-venous ECMO in the most severe forms of ARDS. Selected patients will be those with an ARDS as defined by the usual criteria AND a PaO2 / FiO2 ration lower than 50 mm Hg with FiO2 ≥ 80% for over 3 hours in spite of having optimized their mechanical ventilation and possible resorting to the usual adjunctive therapeutics OR a PaO2 / FiO2 inférieur à 80 mm Hg ratio with FiO2 ≥ 80% for over 6 hours despite having optimized their mechanical ventilation and having possibly resorted to the usual adjunctive therapeutics OR pH < 7.25 for over 6 hours (despite increasing the respiratory frequency to 35/min) thus resulting in a reduction of the Vt and of the PEP to keep the plateau pressure ≤32 cm H2O. In the control group, a conventional treatment of ARDS will be applied, according to the modalities applied in the "maximum pulmonary recruitment group" of the EXPRESS trial. The primary purpose is to show a significant reduction of mortality at D60. At an 80% power and a primary species risk of 5% assuming a 60% mortality in the control group and an absolute mortality reduction of 20% thanks to ECMO, there is an 90% likeliwood of putting an end to the study after including 220 patients, based on a triangular test. This project is part of the REVA network (Research in Mechanical Ventilation).

Study title:
FLORALI study: «Interest of high flow humidified and reheated nasal oxygenotherapy in adult acute hypoxemic and non hypercapnic respiratory failure. Randomized study.»

Lead investigator: :Dr Jean-Pierre FRAT - Medical Critical Care - Rue de la Milétrie - 86021 POITIERS Cedex

Study duration : 2 years

Number of patients: 300

Background:
Acute Respiratory Failure (ARF) hypoxemic and non hypercapnix without any other visceral failure.

Main objective :
Comparing the number of patients requiring a tracheal intubation and an invasive mechanical ventilation in critical care units, during an hypoxemic ARF, dealt with according to three different oxygenotherapy strategies: 1/ VNI-O2-HDN in association, 2/ l’O2-HDN on its own and 3/l’O2 on its own.

Secondary objective:
morbidity, length of ventilation and hospital stay, tolerance of the techniques qpplied and mortality.

Methodology :
Randomized, open, multricentric comparative clinical study on parallel groups.

Inclusion criteria:
:severe dyspnea at rest involving ancillary respiratory muscles, respiratory frequency ≥30 cycles/min, PaO2/FiO2 ≤300. .

Non-inclusion criteria:
Absolute contraindication to VNI, Chronic respiratory pathologies, acute pulmonary oedema ; therapeutic limitation or therapeutic abstention survival ≤ 30 days : urgent indication to tracheal intubation ; PCO2 >45 mmHg ; hemodynamic or neurological failure ; urgent indication to proceed with intubation ; profound aplasia.

Study title:
Results if non invasive palliative ventilation (NIPV) for patients for whom it has been decided not to intubate. OVNI study

Lead investigator: Pr Elie AZOULAY - Medical Critical Care, Hôpital St Louis, APHP.

Study duration :
Start of inclusions in November 2010. Patients inclusion period will be 18 months. The last patient included will be monitored a year later, this study will extend over 30 months. The expected number of included patients is 1000.

Abstract :
Cohort-based, prospective, non interventional and multicentric study.
Any patient receiving NIV, whatever the reason for NIV (weaning, post-operative, securing a fibroscopy), regardless of the duration and its future (whether or not secondarily intubated) can be included in the study.

Justification of the research :
It is necessary to bring recommendations based on a systemic and mulidisciplinary assessment of the use of palliative NIV (pNIV) for patients for whom it has been decided not to intubate. Similarly, it is necessary to customize to patients sub-group that could benefit from pNIV.

Objectives :
The objective of this PHRC is to find answers to the five following questions :

What is the incidence of the decision to limit active therapeutics (LATA) taken as soon as the patient is admitted in the critical care unit?
What is the total number of patients receiving NIV during the study, and amongst those,
what is the total number of patients receiving palliative NIV (pNIV)?
What are the conditions of the decision and implementation of pNIV?
What is the pNIV impact on the quality of life and on the mental health of the patients and on their family (quality of life and anxiety syndrome, depression and stress)?

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Study title:
Prospective randomized study aimed at assessing the impact of humidification on the comfort of patients receiving an oxygenotherapy.

Lead investigator: Laurent POIROUX - Infirmier Senior Nurse – CHU of d'Angers

Study duration :
The anticipated study duration is 3 years.
The anticipated inclusions duration is 2 years.

Study Abstract :
This research work is intended to compare two humification strategies currently implemented during the oxygenotherapy: non heated himidification vs no humidification. The main objective is to demonstrate that in terms of comfort there is no clinical benefit of non heated humidification vs no humidification.

The key assessment parameter will be the overall comfort score measured at the sixth hour into the treatment. This score is based on 15 items rated between 0 (maximum comfort) to 10, each one rated out of 10 (maximum discomfort). The score is therefore comprised between 0 and 150.

This non inferiority trial intends to demonstrate that the absence of humidification is not associated with a discomfort score greater than 30 points vs the discomfort score of patients receiving a humidified oxygenotherapy.

If our assumption is proved right by the results of this study, it will be reasonably recommended to put an end to the humidification system for oxygenotherapy in critical care. Such a recommendation would allow to simplify this very common type of treatment and to significantly reduce its cost.

Study title:
CONTROLED, RANDOMIZED, MULTICENTRIC TRIAL TO TEST THE EFFECT OF EARLY POSITIONING OF PATIENTS IN VENTRAL DECUBITUS ON MORTALITY FOR THOSE SUFFERING FROM PERSISTING AND SEVERE ACUTE RESPIRATORY DISTRESS SYNDROME. PROSEVA study (PROning SEVere Ards patients).

Lead investigator: Claude GUERIN.

Study duration :Start: 1st January 2008 - Estimated end: September 2011.

Study Abstract :
The ventral decubitus (VD) could reduce the mortality of patients suffering from severe acute respiratory distress syndrome (ARDS) by diminishing the potential negative effects of mechanical ventilation and mechanical constraints of « stress » and « strain » imposed on the lung. The trial targets a selected population amongst sick patients. The intended study is a prospective multicentric, randomized, controled single-blind trial aimed at testing the effect of VD on the mortality of patients suffering from severe ARDS (PaO2/FiO2 < 150 avec FiO2 >= 60% and positive expiratory pressure >= 5 cm H2O) receiving a protective mechanical ventilation, notably with a current flow of 6 ml/kg. Patients are randomized in two parallel groups: one VD group where DV is administered by daily sessions of at least 16 consecutive hours and a DD groupe where patients are left in semi-seated position on the back at a 30-45° angle. The initial assessment criterion is mortality at D28. Secondary assessment criteria on mortality at D90 and the incidence of pneumonias acquired during mechanical ventilation. The main assumption is that VD can reduce mortality by 60% to 45%. As a unilateral assumption, at the 5% and 1-b of 90% thresholds, the number of patients to be included is that of 230 by group.