ANZICS CTG Endorsed Study
PHARLAP
A multi-centre RCT of open lung strategy including permissive hypercapnia, alveolar recruitment and low airway pressures in patients with ARDS
Study Description
We have designed a ventilation strategy (PHARLAP) combining tidal volume and plateau pressure limitation with a comprehensive open lung strategy. In a pilot study we demonstrated that this strategy was safe and improved a range of physiological and inflammatory markers in patients with ARDS. We aim to investigate the clinical efficacy of PHARLAP strategy compared to standard mechanical ventilation in ARDS patients. The primary outcome is ventilator free days at day 28. In addition, physiological, inflammatory, clinical and safety economic outcomes variables will be compared between both groups. In a prospective, multi-centre, randomised controlled trial we will enrol 340 adult patients who have developed ARDS within the last 72 hours and randomly allocate them to either the PHARLAP or a control ventilation strategy. PHARLAP strategy: pressure control ventilation to maintain a Pplat ≤ 30 cmH2O and a Vt at 4-6 ml/kg while tolerating respiratory acidosis as long as pH is above 7.15, daily staircase recruitment manoeuvre and individual PEEP titration. Control strategy: low tidal volume based on ARDSnet protocol using volume control ventilation with Vt = 6 ml/kg, Pplat ≤ 30 cmH2O and a FiO2/PEEP titration according to a FiO2/PEEP/oxygen saturation chart. Sedation and weaning from mechanical ventilation and follow-up at 6 months will be the same for both groups.
Management Committee
Carol Hodgson (Co-Chair), Alistair Nichol (Co-Chair), Victoria Bennett (former Project Manager), Yaseen Arabi, Andrew Bersten, Kathy Brickell, Jamie Cooper, John Fraser, Shay McGuinness, Lynne Murray, Rachael Parke, David Tuxen, Shirley Vallance, and Meredith Young (Project Manager).
Administering Institution
ANZIC Research Centre, Monash University
Sample Size
340 patients
Funding
NHMRC Project Grant $997,538
Health Research Council of New Zealand Project Grant $320,961
Health Research Board Clinical Trial Network Award (total $2.3mil (Ireland)) $700,000 (to PHARLAP)
Alfred Hospital Project Grant $121,070
Project Status as of March 2019
The PHARLAP Study recruited 115 patients throughout Australia, New Zealand, Saudi Arabia, Ireland and United Kingdom.
Data was locked on 10th December 2018. Results were presented to sites on 20th December 2018 before presentation at Critical Care Reviews meeting in Belfast on 17th January 2019.
Manuscript has been submitted for publication in early 2019.
We have a planned IPDMA with the ART and OLA study investigators which will inform future trials in this area.
Contact
Meredith Young (email)
Reference
CTG 10-08
NCT01667146