TY - JOUR
T1 - Permissive hypercapnia, alveolar recruitment and low airway pressure (PHARLAP)
T2 - A protocol for a phase 2 trial in patients with acute respiratory distress syndrome
AU - Hodgson, Carol
AU - Cooper, David Jamie
AU - Arabi, Yaseen
AU - Bennett, Victoria
AU - Bersten, Andrew
AU - Brickell, Kathy
AU - Davies, Andrew
AU - Fahey, Ciara
AU - Fraser, John
AU - McGuinness, Shay
AU - Murray, Lynne
AU - Parke, Rachael
AU - Tuxen, David
AU - Vallance, Shirley
AU - Young, Meredith
AU - Nichol, Alistair D.
AU - Australian and New Zealand Intensive Care Society Clinical Trials Group
AU - PHARLAP Study Investigators
AU - Fitzpatrick, Gerry
AU - Maher, Clare
AU - O’Grady, Sarah
AU - Board, Jasmin
AU - McCracken, Phoebe
AU - Gilder, Eileen
AU - McCarthy, Lianne
AU - McArthur, Colin
AU - Chen, Yan
AU - Bellomo, Rinaldo
AU - Eastwood, Glenn
AU - Curley, Ger
AU - Large, Margaret
AU - MacNaughton, Peter
AU - Waddy, Sam
AU - Elloway, Esme
AU - Matheson, Elisha
AU - Schwartz, Kate
AU - Gratrix, Andrew
AU - Smith, Neil
AU - Franke, Uwe
AU - Hugill, Keith
AU - Harrigan, Peter
AU - Hardie, Miranda
AU - Tlayjeh, Haytham
AU - Afesh, Lara
AU - Trinidad, Olivia
AU - Hopkins, Phil
AU - Birch, Sian
AU - Brain, Matthew
AU - Mineall, Sarah
AU - Thomas, Peter
AU - Soar, Natalie
AU - O’Loughlin, Colman
AU - Gilroy, Elaine
AU - Williams, Tony
AU - Hogan, Chantal
AU - Seppelt, Ian
AU - Whitehead, Christina
AU - Moreno Cuesta, Jeronimo
AU - Bakthavatsalam, Dhanalakshmi
AU - Josh, Angaj
AU - Said, Simone
AU - Landoni, Giovanni
AU - Carle, Coralie
AU - Pope, Alan
AU - Corley, Amanda
AU - Williams, Tom
AU - Clarey, Emma
AU - Macken, Lewis
AU - Yarad, Elizabeth
AU - Totaro, Richard
AU - Buhr, Heidi
AU - Zuleika, Mehrun
AU - Montague, Laura
AU - Brickell, Kathy
AU - Nichol, Alistair
AU - Thomas, Matt
AU - Worner, Ruth
AU - Orford, Neil
AU - Bone, Allison
AU - Elderkin, Tania
AU - Jennings, Mick
AU - Reece-Anthony, Rosie
AU - Motherway, Catherine
AU - Hinchion, Rita
AU - Young, Paul
AU - Andrews, Lynne
AU - Davey-Quinn, Alan
AU - Geng, Wenli
AU - Rowan, Kathy
AU - Mouncey, Paul
AU - Bennet, Victoria
AU - Young, Meredith
AU - Hodgson, Carol
AU - Cooper, Jamie
AU - Irish Critical Care Clinical Trial Network
AU - Nichol, Alistair
AU - Doran, Peter
AU - Murray, Patrick
AU - Fahey, Ciara
AU - McAuley, Danny
AU - Laffey, John
PY - 2018/6
Y1 - 2018/6
N2 - Background: Mechanical ventilation is a life-saving intervention that maintains gas exchange in patients with acute respiratory distress syndrome (ARDS); however, it is associated with high mortality and it may augment, or even initiate, lung injury. An open lung ventilation strategy that combines alveolar recruitment manoeuvres with individually titrated positive end-expiratory pressure (PEEP) and targeting lower tidal volumes, or driving pressures by a permissive approach to hypercapnia, may reduce the lung injury associated with mechanical ventilation. This protocol reports the rationale, study design and analysis plan of the Permissive Hypercapnia, Alveolar Recruitment and Low Airway Pressure (PHARLAP) trial. Methods and design: PHARLAP is a phase 2, international, multicentre, prospective, randomised, controlled, parallel-group clinical trial, which aims to determine if staircase alveolar recruitment and individually titrated PEEP, when combined with permissive hypercapnia and low airway pressures, increases ventilator-free days to Day 28 when compared with conventional mechanical ventilation (Acute Respiratory Distress Syndrome Clinical Network [ARDSNet] strategy) in patients with moderate to severe ARDS. This study will enrol 340 patients. The intervention group will receive daily staircase alveolar recruitment manoeuvres with incremental PEEP to a maximum of 40 cmH2O and peak pressures to a maximum of 55 cmH2O. PEEP will be titrated individually against peripheral oxygen saturation, targeting lower tidal volumes by a permissive approach to hypercapnia. In the control group, patients will receive mechanical ventilation following the ARDSNet-ARMA trial protocol, including PEEP titrated with a PEEP/fraction of inspired oxygen (FiO2) chart. Both groups will receive airway pressures ≤ 30 cmH2O and tidal volumes of ≤ 6 mL/kg predicted bodyweight or less. The primary outcome is ventilator-free days to Day 28. Secondary outcomes include oxygenation and lung compliance, intensive care unit (ICU) and hospital length of stay, use of rescue therapies for refractory hypoxaemia, rate of barotrauma, mortality (ICU, hospital and at 28, 90 and 180 days), quality of life and a health economic analysis at 6 months. Discussion: The PHARLAP trial will determine whether the intervention strategy is effective in increasing ventilator-free days in patients with ARDS. If the PHARLAP strategy is proven to improve ventilator-free days, it will provide a strong impetus to conduct an international phase 3 trial to determine the effects of this strategy on mortality. Trial registration: ClinicalTrials.gov identifi er NCT01667146.
AB - Background: Mechanical ventilation is a life-saving intervention that maintains gas exchange in patients with acute respiratory distress syndrome (ARDS); however, it is associated with high mortality and it may augment, or even initiate, lung injury. An open lung ventilation strategy that combines alveolar recruitment manoeuvres with individually titrated positive end-expiratory pressure (PEEP) and targeting lower tidal volumes, or driving pressures by a permissive approach to hypercapnia, may reduce the lung injury associated with mechanical ventilation. This protocol reports the rationale, study design and analysis plan of the Permissive Hypercapnia, Alveolar Recruitment and Low Airway Pressure (PHARLAP) trial. Methods and design: PHARLAP is a phase 2, international, multicentre, prospective, randomised, controlled, parallel-group clinical trial, which aims to determine if staircase alveolar recruitment and individually titrated PEEP, when combined with permissive hypercapnia and low airway pressures, increases ventilator-free days to Day 28 when compared with conventional mechanical ventilation (Acute Respiratory Distress Syndrome Clinical Network [ARDSNet] strategy) in patients with moderate to severe ARDS. This study will enrol 340 patients. The intervention group will receive daily staircase alveolar recruitment manoeuvres with incremental PEEP to a maximum of 40 cmH2O and peak pressures to a maximum of 55 cmH2O. PEEP will be titrated individually against peripheral oxygen saturation, targeting lower tidal volumes by a permissive approach to hypercapnia. In the control group, patients will receive mechanical ventilation following the ARDSNet-ARMA trial protocol, including PEEP titrated with a PEEP/fraction of inspired oxygen (FiO2) chart. Both groups will receive airway pressures ≤ 30 cmH2O and tidal volumes of ≤ 6 mL/kg predicted bodyweight or less. The primary outcome is ventilator-free days to Day 28. Secondary outcomes include oxygenation and lung compliance, intensive care unit (ICU) and hospital length of stay, use of rescue therapies for refractory hypoxaemia, rate of barotrauma, mortality (ICU, hospital and at 28, 90 and 180 days), quality of life and a health economic analysis at 6 months. Discussion: The PHARLAP trial will determine whether the intervention strategy is effective in increasing ventilator-free days in patients with ARDS. If the PHARLAP strategy is proven to improve ventilator-free days, it will provide a strong impetus to conduct an international phase 3 trial to determine the effects of this strategy on mortality. Trial registration: ClinicalTrials.gov identifi er NCT01667146.
KW - Mechanical ventilation
KW - gas exchange
KW - ARDS
UR - http://www.scopus.com/inward/record.url?scp=85048033136&partnerID=8YFLogxK
UR - https://ccr.cicm.org.au/journal-editions/2018/june/20
M3 - Article
C2 - 29852853
AN - SCOPUS:85048033136
VL - 20
SP - 139
EP - 149
JO - Critical Care and Resuscitation
JF - Critical Care and Resuscitation
SN - 1441-2772
IS - 2
ER -