Prospective, Randomized, Multi-Center Trial of Lateral Trendelenburg
Versus Semi-Recumbent Body Position
in Mechanically Ventilated Patients For
The Prevention of Ventilator-Associated Pneumonia
Version 2.1.1 Date of Last Update March 28, 2014
Designed by the Gravity-VAP Network
This Project is endorsed by the ECCRN of the European Society of Intensive Care Medicine
1 Gravity-VAP trial - NCT01138540 Version 2.1.1
Prospective, Randomized, Multi-Center Trial of Lateral Trendelenburg versus Semi-Recumbent Body
Position in Mechanically Ventilated Patients For
The Prevention of Ventilator-Associated Pneumonia
(The Gravity-VAP Trial)
Designed by the Gravity-VAP Network
Date: Friday, March 28, 2014
Protocol Title: Prospective, Randomized, Multi-Center Trial of Lateral Trendelenburg versus Semirecumbent Position Body Position in Intubated Patients and Ventilator-Associated Pneumonia
Abbreviated Title: The Gravity-VAP Trial.
Identifying words: Ventilator-Associated Pneumonia, Semirecumbent Position, Trendelenburg
Investigators of the American-Italian-Spanish Gravity-VAP network (sorted by last name):
Lorenzo Berra, MD Massimo Cressoni, MD
Gianluigi Li Bassi, MD, PhD Mauro Panigada, MD Alberto Zanella, MD
Luciano Gattinoni, MD Theodor Kolobow, MD
Antoni Torres, MD, PhD Jeanine Wiener-Kronish, MD
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Associate Investigators
1. Massimo Antonelli, Director Istituto di Anestesiologia e Rianimazione, Universit Cattolica del Sacro Cuore, Policlinico A. Gemelli, Roma, Italy
2. Giovanna Mercurio, Istituto di Anestesiologia e Rianimazione, Universit Cattolica del Sacro Cuore, Policlinico A. Gemelli, Roma, Italy
3. Marco Morelli, Director Unita di Anestesia e Terapia Intensiva, Ospedale Nuovo del Mugello, Borgo San Lorenzo, Italy
4. Vieri Parrini, Unita di Anestesia e Terapia Intensiva, Ospedale Nuovo del Mugello, Borgo San Lorenzo, Italy
5. Antonino Pistilli, Director Unita di Anestesia e Terapia Intensiva, Arcispedale S. Maria Nuova, Reggio Emilia, Italy
6. Giovanni Salati, Unita di Anestesia e Terapia Intensiva, Arcispedale S. Maria Nuova, Reggio Emilia, Italy
7. Sergio Livigni, Director Unita di Anestesia e Terapia Intensiva, Ospedale San Giovanni Bosco, Torino, Italy
8. Daniela Silengo, Unita di Anestesia e Terapia Intensiva, Ospedale San Giovanni Bosco, Torino, Italy
9. Giorgio Iotti, Director Unita di Anestesia e Terapia Intensiva, Policlinico San Matteo, Pavia, Italy
10. Alessandro Amatu, Unita di Anestesia e Terapia Intensiva, Policlinico San Matteo, Pavia, Italy 11. Andrea Ballotta, Director Unita di Anestesia e Terapia Intensiva, Gruppo Ospedaliero San
Donato, San Donato Milanese, Italy 12. Hassan Kandil, Unita di Anestesia e Terapia Intensiva, Gruppo Ospedaliero San Donato, San
Donato Milanese, Italy 13. Gabriella Moise, Director Unita di Anestesia e Terapia Intensiva, Ospedale Citta di Sesto san
Giovanni, Sesto San Giovanni, Italy 14. Vesna Bumbasirevic, Director Department of Critical Care Medicine, Clinical Center of Serbia,
Belgrade, Serbia 15. Bojan Jovanovic, Department of Critical Care Medicine, Clinical Center of Serbia, Belgrade,
Serbia 16. Andrea Ballotta, Director Unita di Anestesia e Terapia Intensiva, Azienda Ospedaliera-
Universitaria di Modena, Modena, Italy 17. Emanuela Biagioni, Unita di Anestesia e Terapia Intensiva, Azienda Ospedaliera-Universitaria
di Modena, Modena, Italy 18. Patrick Meybohm, Director Department of Critical Care Medicine, University Hospital
Frankfurt, Frankfurt, Germany 19. Karin Pense, Department of Critical Care Medicine, University Hospital Frankfurt, Frankfurt,
Germany 20. Vladimir Gasparovic, Director Department of Critical Care Medicine, University Hospital
Center Zagreb, Zagreb, Croatia 21. Jeksa Babel, Department of Critical Care Medicine, University Hospital Center Zagreb, Zagreb,
Croatia
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Statistical Analysis:
22. Dario Consonni, Unit of Epidemiology, Department of Preventive Medicine, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via San Barnaba 8, 20122 Milano, Italy
Research Contact: Gianluigi Li Bassi, MD, PhD Servei de Pneumologia i Allrgia Respiratria Hospital Clnic 170 Villarroel street, 6/8 2nd floor 08036 Barcelona SPAIN Voice/Fax: 0034 932275549 Email: [email protected] Web: www.idibapsrespiratoryresearch.org
Mauro Panigada, MD U.O. Anestesia e Rianimazione Fondazione IRCCS Ospedale Maggiore Policlinico Mangiagalli e Regina Elena di Milano Padiglione Guardia-Accettazione/PS Via F. Sforza 35 20122 Milano Voic/Fax: +39 (02) 55033230 Email: [email protected]
Duration of Study: Five years
Number and Type of Subjects: 800 Critically ill patients, intubated and on mechanical ventilation
Multi-Institutional Project: Yes
4 Gravity-VAP trial - NCT01138540 Version 2.1.1
SUMMARY
Prcis ......................................................................................................................................................... 6 1 Background ............................................................................................................................................ 8
1.1 Pathogenesis of ventilator-associated pneumonia and rationale for the semi-recumbent position 8 1.2 VAP and attributable mortality ..................................................................................................... 10 1.3 Economic impact of VAP ............................................................................................................. 10 1.4 Published human studies on the role of the stomach in the pathogenesis of ventilator-associated
pneumonia and the semi recumbent position ...................................................................................... 11 1.4a Role of the stomach as a reservoir of pathogenic bacteria: ..................................................... 12 1.4b Role of the oropharynx as a reservoir of pathogenic bacteria: ............................................... 27 1.4g Summary of the role of the semirecumbent position in prevention of VAP: ......................... 33
1.5 Laboratory studies conducted at the National Institutes of Health to assess effects of gravity in the pathogenesis of ventilator associated pneumonia ......................................................................... 34
1.5a Summary of results from laboratory studies conducted at the National Institutes of Health . 39 2 Rationale of the study .......................................................................................................................... 40 3 Objectives ............................................................................................................................................ 42 4 Study Design ........................................................................................................................................ 42
4.1 End points ..................................................................................................................................... 42 Primary end point ............................................................................................................................ 42 Secondary end points ...................................................................................................................... 42
5 Subject Accrual .................................................................................................................................... 44 5.1 Screening and Research Centers ................................................................................................... 44 5.2 Inclusion Criteria .......................................................................................................................... 44 5.3 Exclusion Criteria ......................................................................................................................... 44
6 Study procedures .................................................................................................................................. 46 6.1 Body Positions .............................................................................................................................. 46
6.1a Semi-recumbent position: ....................................................................................................... 46 6.2 Preventive strategies ..................................................................................................................... 47 6.3 Respiratory gases humidification .................................................................................................. 47 6.4 Enteral Nutrition ........................................................................................................................... 47 6.5 Weaning protocol .......................................................................................................................... 47 6.6 Ventilator-associated pneumonia diagnosis .................................................................................. 50 6.7 Data Collection ............................................................................................................................. 50
6.7a Assessments during enrollment (Appendix C, Baseline Assessment): ................................... 50 6.7b Daily assessments during the study (Appendix C, Daily Assessment) up to 14 days: ........... 51
6.8 Special Clinical and Laborat
