Awake Prone Positioning to Reduce Invasive VEntilation in COVID-19 Induced Acute Respiratory failurE
Phase: NA
Conditions: ARDS, Human, Mechanical Ventilation Complication, COVID19
Sponsor: University College Hospital Galway

APPROVE-CARE-V2 October 2020 
Awake Prone Positioning to Reduce Invasive VEntilation in COVID-
19 Induced Acute Respiratory failure (APPROVE-CARE)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

APPROVE-CARE-V2 October 2020 
Study Summary 
The coronavirus disease 2019 (COVID-19) outbreak is a pandemic associated with a pneumonia 
which can worsen rapidly into respiratory failure known as acute respiratory distress syndrome 
(ARDS). There is a high rate of mortality in patients with severe respiratory failure requiring 
mechanical ventilation. Adjunctive therapies constitute an important part of the management of 
early moderate to severe ARDS. In patients with confirmed moderate-severe ARDs receiving invasive 
mechanical ventilation, prone position promotes lung homogeneity, improves gas exchange and 
respiratory mechanics permitting reduction of ventilation intensity, and reducing lung injury. Prone 
positioning has been demonstrated to save lives and is recommended in evidence-based guidelines 
for the management of moderate-severe ARDS.  
The use of proning outside of mechanically ventilated patients to improve gas exchange and reduce 
the end for invasive ventilation has not been extensively studied outside of case series. Maintaining 
self ventilation is associated with increased aeration of dependent lung regions, less need for 
sedation, improved cardiac filling, and better matching of pulmonary ventilation and perfusion and 
thus oxygenation.  
In this protocol, we outline details for a randomized clinical trial to determine whether placing 
patients who have hypoxemia related to COVID19 into a prone position can improve oxygenation 
and reduce the requirement for mechanical ventilation. If effective, this simple intervention could be 
widely and rapidly implemented, potentially reducing the need for ICU admission and invasive 
ventilation, and potentially even saving lives.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

APPROVE-CARE-V2 October 2020 
 
1. Study team- Galway 
Intensive Care Medicine  
Principal Investigator: Dr. Bairbre McNicholas  
Dr. Camilla Giacommini  
Dr. David Cosgrove  
Dr. John Laffey  
2. Study sponsor  
Clinical Research Facility, National University of Ireland, Galway  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

APPROVE-CARE-V2 October 2020 
 
3. Background and rationale  
a. COVID-19 and Hypoxemia  
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) first appeared in Wuhan China in 
December 2019. It has since spread and was declared a worldwide pandemic by the World Health 
Organisation in March 2020.(1) Its main route of infection are respiratory droplets and contact 
transmission. Many infections will be asymptomatic or mild, but a subset require hospitalization and 
admission to critical care is associated with a high morbidity and mortality from the disease. Acute 
respiratory distress syndrome requiring mechanical ventilation is associated with a 40-60% 
mortality. To date, there are no specific pharmacological therapies currently although many are 
being trialled.(2)  
b. Prone position physiology  
Prone position is a non-pharmacological treatment used in patients with severe ARDS which has 
proven mortality benefits in this population. (3)  Physiological studies have shown differences in 
ventilation pressures in distinct regions of the chest depending on whether one is in the prone or 
supine position. While breathing in a supine position, the ventral chest wall is lifted by a driving 
pressure driven by the difference between pleural pressure and atmospheric pressure (Ppleural - 
Patmospheric): the diaphragm moves caudally (Ppl - Pabdomen), and the dorsal chest wall moves 
minimally as lying in contact with a rigid surface. In the supine position, there is a reduction in 
alveolar size from sternum to vertebra in the supine position at the end of the expiration. This 
phenomenon has also been clearly identified with CT scans (6-9), and leads to a greater expansion of 
the nondependent regions and lesser expansion of the dependent parenchyma (6-8).  
Contrarily while prone, the dorsal chest wall lifts, the diaphragm shifts similarly to supine position, 
and the ventral chest wall, now in contact with the firm surface of the bed, is impeded from 
expanding (8). In the prone position the gravitational forces compress the ventral region, but this 
effect is damped by regional expansion due to shape matching between lung parenchyma and 
vertebrae. As the lung mass is anatomically greater in dorsal regions (nondependent when prone) 
than in ventral region (dependent when prone), the increased aeration and recruitment of the 
dorsal region tends to exceed the decreased aeration and derecruitment of the ventral regions. That 
generates a more homogenous ventilation across the entire lung(6). Furthermore, when an 
individual is supine the heart compresses the medial posterior lung parenchyma (10) and the 
diaphragm compresses the posterior-caudal lung parenchyma, with the abdominal contents 
displacing the diaphragm cranially (8,10). Compression by either the heart and/or the diaphragm 
may exaggerate dependent lung collapse in the supine position (9). During prone ventilation, the 
heart becomes dependent, lying on the sternum, potentially decreasing medial-posterior lung 
compression (10). In addition, the diaphragm is displaced caudally, decreasing compression of the 
posterior-caudal lung parenchyma. A further advantage observed in prone position is both an 
improvement of ventilation/perfusion match and an increase in cardiac output: the latter is thought 
to be due to the effect of increased lung recruitment and reduction in hypoxic pulmonary 
vasoconstriction, resulting in increases in right ventricular preload and decreased right ventricular 
afterload and a decrease in pulmonary vascular  resistance (11,12). An important recent study by 
Guerin et al. showed that prone positioning applied for at least 16 hours per day in patients with 
ARDS and PaO2/FiO2 < 150 mmHg significantly reduced 28-day mortality (16% vs 32%).(15) From 
currently available evidence, prone positioning may be of value even if there is no improvement in 
gas exchange [10-14].  

APPROVE-CARE-V2 October 2020 
 
c. Experience with awake prone positioning  in self-ventilating patients  
Prone position results in improved ventilation and blood flow ratios. In mechanically ventilated and 
often paralysed patients, proning requires a high nursing input and patients are at risk for pressure 
sores related to the position. These issues are less pertinent in patients who are self-ventilating. 
Proning self-ventilating patients is not commonly carried out as patients with reduced oxygenation 
generally require assisted ventilation. However, avoidance of mechanical ventilation by improving 
oxygenation may be importance in COVID19 as outcomes for patients who require mechanical 
ventilation are poor and resources become limited. We have noted improvement with proning in 
self ventilating patients at both ward level and in the ICU for patients with confirmed COVID19 and 
in a patient without COVID19 with ARDS.  
d. Rationale for treating patients with COVID19 pneumonia with awake prone 
positioning 
Patients with COVID19 that require invasive mechanical ventilation have a high mortality. We 
hypothesis that early proning for self-ventilating patients with suspected or confirmed COVID19 who 
have hypoxemia (spO2 <94%) despite high flow nasal cannula (fiO2 40%) will result in improved 
oxygenation, reduced work of breathing and a reduced the need for invasive mechanical ventilation.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

APPROVE-CARE-V2 October 2020 
 
4. Study Aims and Objective  
a. Research hypothesis  
In patients that are hypoxic secondary to COVID19, the use of prone positioning will result in a 
reduction in requirement for invasive mechanical ventilation. Key secondary hypothesis include that 
prone positioning will result reduced requirement for assisted ventilation, in improved oxygenation 
as measured by either S/F or P/F ratio, reduced work of breathing. 
b. Study aim  
The study aims to assess the effect of prone positioning in patients who have hypoxemia related to 
COVID19 on:  
 
need for mechanical ventilation  
 
Improvement in oxygenation as measured by S/F or P/F ratio  
 
Patient work of breathing as measured by the respiratory distress observation scale  
 
tolerability of the position as measured by the total number of hours in prone position  
 
c. Study objectives  
Primary objective  
To assess the effect of awake prone positioning on requirement for mechanical ventilation or death 
in patients with suspected or confirmed COVID 19 infection.  
Secondary objective  
To assess the effect of prone positioning on:  
 
Length of time tolerating prone positions measured in minutes from prone to request to 
return to supine position or emergency repositioning if required  
 
SpO2: FiO2 ratio (as a surrogate marker of P/F ratio) measured before proning and 1 hours 
after proning or P/F ratio where arterial line available  
 
Number requiring increase in ventilatory assistance (CPAP+BIPAP+IMV etc)  
 
Work of breathing assessment  
 
5. Study Details 
a. Study design  
Multi centre open label randomized controlled study in which patients are randomized to awake 
prone positioning or standard care. This trial is registered with ClinicalTrials.gov (NCT04347941). This 
trial is part of a prospective meta-trial listed in appendix 1.  
b. Study timeline  
Study will begin 5th june 2020 and until 28 days following the last enrolled patient  
c. End of study  
Study will continue until 28 days after the last enrolled patient or for 6 months until October 2020, 
depending on levels of enrolment.  

APPROVE-CARE-V2 October 2020 
 
6. Study outcome measure  
a. Primary outcome measure  
Requirement for invasive mechanical ventilation or death by 28 days post enrolment  
b. Secondary outcome measure  
 
Length of time tolerating prone positions measured in minutes from prone to request to 
return to supine position or emergency repositioning if required  
 
SpO2 : FiO2 ratio (as a surrogate marker of P/F ratio) measured before proning and 1 hours 
after proning or P/F ratio where arterial line available  
 
Number requiring increase in ventilatory assistance (CPAP+BIPAP+IMV etc)  
 
7. Patient Eligibility  
a. Study setting  
A monitored ward or ICU in which patients with confirmed or suspected COVID19 are receiving high 
flow nasal cannula 
b. Study population  
Patients who have suspected or confirmed COVID19 who have infiltrates on CXR and who have an 
oxygen requirement of >4L to keep oxygen saturations about 94% using high flow nasal cannula  
c. Eligibility criteria  
Inclusion criteria  
Suspected or confirmed COVID19 infection  
Bilateral Infiltrates on CXR  
SpO2 <94% on FiO2 40% by high flow nasal cannula  
Able to provide written informed consent  
Exclusion criteria  
Age <18  
RR>40  
Uncooperative or likely to be unable to lie on abdomen for 16 hours  
Immediate need for intubation 
SBP<80 
Vomiting or bowel obstruction  
Palliative care  
Multiorgan failure  
Standard contraindications to prone positioning include the presence of an open abdominal 
wound, unstable pelvic fracture, spinal lesions and instability, pregnancy > 20/40 gestation 
and brain injury without monitoring of intracranial pressure.  
d. Co-enrolment guidelines  
Patients will be eligible for inclusion in other studies  
 

APPROVE-CARE-V2 October 2020 
 
8. Patient screening, consent and recruitment  
a. Patient screening  
All patients admitted to a COVID19 ward, COVID ICU or HDU will be screened for inclusion in the 
study.  
b. Informed consent procedure  
As patients will be self-ventilating, written informed consent or witnessed telephone consent to 
reduce fomite transmission will be obtained for each patient enrolled in the study. A patient 
information leaflet will be given to all patients screened as eligible. After a period of time to read 
and consider the information leaflet time will be given for questions, and then if the patient 
consents to be involved, written consent will be obtained. Due to the risk of fomite result of 
informed consent will be witnessed and recorded in the patient chart. The original consent form will 
be disposed of in yellow waste from the patient room, which should be destroyed.  
9. Assignment of intervention  
Awake prone positioning will be performed before or 1 hour after meal. Call bell will be given to the 
patient and an oxygen probe will be attached to the patient to monitor spO2 during the procedure. 
Before PP, all the I.V. lines and nasal cannula will be checked by clinicians. Awake prone positioning 
will be performed by patient under the supervision of clinicians. Assistance will be offered if needed. 
If tolerated, PP will be maintained for at least 30 minutes, until the patients feel tired to keep that 
position. Patients will be informed to maintain prone position as long as they can. FIO2 will be 
adjusted to maintain SpO2 at 92-95%. Protocol for sedation and comfort evaluation during PP: No 
sedation will be used during the PP on ward. The patients are monitored by bedside respiratory 
therapist and nurses for their comfort and tolerance for the PP at 5mins, 30 minutes after PP for the 
first PP in each day.  
a. Withdrawal criteria  
 
Patients cannot tolerate HFNC or prone position for 30 mins  
 
Patients experience any side effects during prone position, including vomit, dizzy, 
hypotension, etc.  
 
b. Weaning criteria  
 
Patients’ PaO2/FIO2 > 300, or SpO2/FIO2 > 340  
 
c. Treatment Failure Criteria  
Failure criteria: treatment failure is defined as one of the following criteria:  
 
Signs of persisting or worsening respiratory failure, defined by at least two of the following 
criteria:  
- 
Respiratory rate above 40 cycles/min  
- 
Lack of improvement of signs of respiratory-muscle fatigue  
 
-Development of copious tracheal secretions  
 
-Respiratory acidosis with a pH below 7.35  
 
-SpO2 below 90% at FIO2 ≥ 0.8 for more than 5 min without technical dysfunction  

APPROVE-CARE-V2 October 2020 
 
Hemodynamic instability defined by a SBP below 90 mmHg, MBP below 65 mmHg or 
requirement for vasopressor;  
 
Deterioration of neurologic status (with AVPU to pain). For patients who meet the failure 
criteria in the standard treatment and PP groups, a trial of NIV will be allowed according to 
the physician’s preference in patients with signs of persisting or worsening respiratory 
failure and no other organ dysfunction before performing endotracheal intubation and 
invasive ventilation. Reasons for intubation will be recorded as well.  
 
d. Allocation and Randomisation 
Within 6 hr of fulfilling inclusion criteria, a patient will be randomly allocated either to the prone 
positioning group or the control group (HFNC alone with no prone positioning therapy). Patients will 
be randomly allocated to either arm of the study at a ratio based on a 1:1 basis using a REDCAP 
randomisation process. Randomization will be stratified by site using tables of random permutations 
using the RECAP database for randomization. The random block length is 4, and random numbers 
are generated by computer.  
e. Blinding  
It is not feasible to blind staff or patients as to the procedure. Study data will be blinded for the 
purposes of analyses, assigned as group 1 or group2 rather than prone / not proned.  
10. Schedule of assessment  
a. Data collection and management  
Data will be collected using an electronic case report form hosted in UCD. Details of CRF attached in 
appendix B. No patient identifiers will leave hospital unit and all data sent to CRF at NUI Galway will 
be pseudoanonymised. A collaborative data sharing agreement with UCD and NUI Galway has been 
developed. Aggregated data will be shared with investigators of the Awake Prone Positioning in 
COVID Meta-Trial for interim analysis and Anonymised data without personal identifying features 
will be sent for final analysis and co-reporting of outcomes.  
b. Data quality  
Data quality will be audited by the CRF at NUI Galway as responsibility of the study sponsor.  
11. Statistical Considerations  
a. Sample size  
From ICNARC data on patients admitted to ICU with COVID19, 60% required advanced respiratory 
support. From this, we propose a 60% intubation rate in this cohort as defined above and that 
proning will decrease it to 40%. From this, 97 patients per group for a beta of 0.2 and alpha 0.05, 
requiring the need to recruit 196 patients. Interim analysis of data will be conducted using 
aggregated data as part of the Awake Prone Positioning in COVID Meta-Trial.  
b. Analysis population  
Data will be analysed on an intention to treat basis with all data for patients who consented to be 
involved included in baseline data analysis. Outcome data will be analysed for all patients who were 
positioned in the prone position for any length of time. A further per protocol analysis will be carried 
out on all patients who tolerated at least 1 hour of the daytime proning time and at least 2 hours of 
the night time proning period in any 24 hour period. Patients who were rescue proned will be 
considered a protocol deviation and will be studies as a group. Definition of the two groups: The 

APPROVE-CARE-V2 October 2020 
patients who receive the prone positioning are classified as prone positioning group. The patients 
who receive HFNC alone are classified as HFNC group. Comparisons between the two groups: 
Quantitative continuous variables are given as either means (±SDs) or medians (with inter-quartile 
ranges) are compared using the unpaired Student’s t test or the Mann-Whitney test. Qualitative or 
categorical variables are compared with the chis quare test or the Fisher’s exact test. ANOVA for 
paired tests to compare the same variables collected at different time points are used. The 
cumulative probability of remaining on spontaneous breathing are compared with the Kaplan-Meier 
estimate of survival and the log-rank test to compare the two groups. Univariate and multivariate 
analyses of risk factors for PP failure are performed with logistic regression. All analyses are in 
intention to treat, and the level of significance is set at 0.05. 
c. Missing data  
Missing data will be completed using last observation carried forward and the percentage of 
datasets with full or missing data will be reported.  
12. Data monitoring  
a. Data access and Monitoring arrangement  
The eCRF has an audit trail in place, participating centres only have accounts available for delegated 
people and specific login accounts are created to only edit for their own site. External monitors can 
only view data and enter queries, they cannot change data. No directly identifiable data will be 
stored in the eCRF, e.g. only year of birth and no date of birth will be captured Audit trail in place 
(eCRF) compliant with 21 CFR part 11. The database is compliant with the EU Directive on data 
protection 95/46/EC. eCRF only accessible via site-specific (password-regulated) delegated log-in. 
(21 CFR part 11 compliance). Also compliant with the EU Directive on data protection 95/46/EC. A 
Standard contractual clauses for the transfer of personal data from the Community to third 
countries (controller to controller transfers) has been signed  
13. Regulation, Ethics and Governance  
a. Regulatory and ethics approval  
Study has been approved by Galway University Hospitals Research ethics committee and the 
National research ethics committee (CA2352,  20-NREC-COV-054).  
b. Protocol compliance  
A Request for sponsorship from the CRFG at NUI Galway has been sought which will provide the 
necessary manpower for trial oversight, quality, statistical analysis. Online training on study protocol 
will be conducted prior to site initiation. Investigators will be available for any data entry queries or 
clinical concerns. 
c. Good clinical practice  
All individuals who will participate in conducting this study and have signed a delegation log will 
require an up to date certificate of good clinical practice.  
d. Indemnity  
Patients will be covered under the HSE Clinical Indemnity Scheme and by indemnity provided by the 
National University of Ireland, Galway  

APPROVE-CARE-V2 October 2020 
e. Patient confidentiality  
A Data privacy impact assessment has been filed for the study. Patient confidentiality will be 
maintained by keeping data collected in the study coded. The key will be at the local study site 
where patient is included. No Personal details or identifying data will be transferred from the site to 
the sponsor where the data will be analysed. The coded data will be securely entered via the 
electronic case report form which will be managed by NUI Galway. The need data controlled will be 
the principal investigator, associate investigators, biostatisticians affiliated with NUI Galway. The site 
lead will have received training in regard to the requirements under GDPR that relate to health 
research. A data protection impact assessment has been completed and submitted to the SAOLTA 
data protection officer.  
f. Data access  
The data will be collected using a paper or digital case report form and the data will be collected in a 
coded form. The key for the data will be at the local study site in which the patient is included. Data 
will only be stored on protected and accredited servers. No personal details or identifying data will 
be transferred from the site to the coordinating centre at NUI Galway where the data will be 
analysed. The data will be retained for 15 years or as long as local legislation requires. Confidentiality 
will be maintained by sponsor only having access to coded data and the key only available at the 
local site. Clinical notes will need to be reviewed by the clinical research team on site. No identifiable 
data will be collected in the process. Information regarding current clinical presentation and clinical 
trajectory over the course of hospitalization will be collected Information regarding the patient will 
be taken out of the record and added to the case report form. 
g. Record retention  
Participants are requested to give consent to store their data for 15 years (without this permission, 
patient cannot participate). Next, participants are asked whether there coded data can be used for 
future research in the field of lung infections (data will also be stored 15 years for this purpose, with 
extra consent as described).  
g. Competing interest  
The principal investigators have no conflict of interest related to this study.  
h. Data safety and Monitoring Board 
Independent Investigators to fulfill data safety and monitoring board the study have been selected. 
This will be performed by Prof. Andrew Smyth, Galway University Hospitals, Dr. Rabia Hussein, 
Clinical research facility, UCD. A charter outlining the roles and responsibilities of the DSMB has been 
created. They will meet on-line after first patient has been enrolled.  
14. Dissemination  
Results of both registry and randomised controlled trial will be published in an international journal 
following peer review. To incentivise participation in the study, centres that recruit a patient will be 
permitted to have one author on final publication. For each additional 10 patients recruited, a 
further author from that centre will be added to the authors list.  
 
 

APPROVE-CARE-V2 October 2020 
 
References  
1) Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in 
Wuhan, China [supplementary appendix appears online]. Lancet 2020;395:497-506  
2) Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with 
COVID- 19 in Wuhan, China: a retrospective cohort study [supplementary appendix appears online]. 
Lancet. E-pub Date: [published online ahead of print] March 2020  
3) Gattinoni et al. “Prone Position in Acute Respiratory Distress Syndrome. Rationale, Indications, 
and Limits”. Am J Respir Crit Care Med 2013; 188:11.  
4) Hubmayr RD. “Perspective on lung injury and recruitment: a skeptical look at the opening and 
collapse story”. Am J Respir Crit Care Med 2002;165:1647–1653.  
5) Pelosi P, D’Andrea L, Vitale G, Pesenti A, Gattinoni L. “Vertical gradient of regional lung inflation in 
adult respiratory distress syndrome”. Am J Respir Crit Care Med 1994;149:8–13.  
6) Gattinoni L, Pelosi P, Vitale G, Pesenti A, D’Andrea L, Mascheroni D. “Body position changes 
redistribute lung computed-tomographic density in patients with acute respiratory failure”. 
Anesthesiology 1991;74:15–23.  
7) Gattinoni L, D’Andrea L, Pelosi P, Vitale G, Pesenti A, Fumagalli R. “Regional effects and 
mechanism of positive end-expiratory pressure in early adult respiratory distress syndrome”. JAMA 
1993;269:2122–2127.  
8) Lai-Fook SJ, Rodarte JR. “Pleural pressure distribution and its relationship to lung volume and 
interstitial pressure”. J Appl Physiol 1991;70(3):967.  
9) RK, Hubmayr RD. “The prone position eliminates compression of the lungs by the heart”. Am J 
Respir Crit Care Med 2000;161:1660–1665.  
10) Agostoni E, Mead J. “Statics of the respiratory system”. In: “Handbook of Physiology”, Macklem 
P, Mead J (Eds), American Physiologic Society, Bethesda 1986, p.387.  
11) Puybasset L, Cluzel P, Chao N, Slutsky AS, Coriat P, Rouby JJ. “A computed tomography scan 
assessment of regional lung volume in acute lung injury. The CT Scan ARDS Study Group”. Am J 
Respir Crit Care Med 1998;158(5 Pt 1):1644.  
12) Malbouisson LM, Busch CJ, Puybasset L, Lu Q, Cluzel P, Rouby JJ. “Role of the heart in the loss of 
aeration characterizing lower lobes in acute respiratory distress syndrome. CT Scan ARDS Study 
Group”. Am J Respir Crit Care Med 2000;161(6):2005.  
13) Jozwiak M, Teboul JL, Anguel N, Persichini R, Silva S, Chemla D, Richard C, Monnet X. “Beneficial 
hemodynamic effects of prone positioning in patients with acute respiratory distress syndrome”. Am 
J Respir Crit Care Med. 2013;188(12):1428.  
14)Nyrén S, Radell P, Lindahl SG, Mure M, Petersson J, Larsson SA, Jacobsson H, Sánchez-Crespo A. 
“Lung ventilation and perfusion in prone and supine postures with reference to anesthetized and 
mechanically ventilated healthy volunteers”. Anesthesiology. 2010 Mar;112(3):682-7.  
15) Guerin, C., et al., Prone positioning in severe acute respiratory distress syndrome. N Engl J Med, 
2013. 368(23): p. 2159-68.  

APPROVE-CARE-V2 October 2020 
16)ElectricalImpedanceTomographyforCardio-
PulmonaryMonitoring.PutensenC,HentzeB,MuensterS,MudersT.JClinMed.2019Aug7;8(8):1176.doi:1
0.3390/jcm8081176. 
 
 
Appendix 1 
Chicago: Jie Li, Sara Mirza, David Vines, Ahmad A Elshafei, Hangyong He, Tyler Weiss, Jonathan Brayd 
Scott, Lauren J Harnois, Ramandeep Kaur, Amnah A Alolaiwat  
 
 
France: Elsa Tavernier, Stephan Ehrmann, Yonatan Perez, Jie Li, Jean-Pierre Frat (Scientific 
committee), List of principal investigators among 13 centers (TELLIER Anne Charlotte, REIGNIER Jean, 
GUITTON Christophe, NAY Mai-Anh, L’HER Erwan, THILLE Arnaud, DELLAMONICA Jean, PLANTEFEVE 
Gaëtan, ROUX Damien, DELBOVE Agathe, VOIRIOT Guillaume, NSEIR Saadalla) 
.  
 
Ireland: Bairbre McNicholas, David Cosgrave, Camille Giacomini, John Laffey,  List of investigators 
among 10 centres 
 
Quebec : Ivan Pavlov, Philippe Rola, Dev Jayaraman, Patrice Plamondon, Alexandra Hamel, Sean 
Gilman, Vincent Bouchard, Jason Kirkness 
 
Spain: Oriol Roca, Marina García-de-Acilu, Gonzalo Hernández, Joan R Masclans, Sergi Martí, List of 
investigators among 4 centres.