PHARLAP
Trial question
What is the role of maximal recruitment open lung ventilation in patients with ARDS?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
42.4% female
57.6% male
N = 115
115 patients (48 female, 66 male)
Inclusion criteria: adult patients with moderate-to-severe ARDS who were mechanically ventilated for < 72 hours
Key exclusion criteria: ventilation for > 10 days; evidence of barotrauma; active bronchospasm or significant obstructive or restrictive pulmonary disease; any suspicion of raised ICP; unstable cardiovascular status
Interventions
N=58 PHARLAP intervention (maximal lung recruitment, titrated positive end expiratory pressure and further tidal volume limitation for up to the first 5 days)
N=57 control (protective ventilation based on ARDS Network protocol)
Primary outcome
Ventilator-free days at day 28
16
14.5
16.0 days
12.0 days
8.0 days
4.0 days
0.0 days
PHARLAP
intervention
Control
No significant
difference ↔
No significant difference in ventilator-free days at day 28 (16 days vs. 14.5 days; AD 1.5 days, 95% CI -41.26 to 44.26)
Secondary outcomes
No significant difference in death at day 28 (24.6% vs. 26.8%; ARD -2.2, 95% CI -17.47 to 13.07)
No significant difference in length of stay in the ICU (11.1 days vs. 13.8 days; AD -2.7 days, 95% CI -15.4 to 10)
No significant difference in length of hospital stay (20.1 days vs. 17.9 days; AD 2.2 days, 95% CI -13.82 to 18.22)
Safety outcomes
No significant differences in serious adverse events, barotrauma, pneumothorax requiring chest drain, bradycardia, severe hypotension.
Significant differences in new cardiac arrhythmia (29% vs. 13%), new inhaled nitric oxide cases (10.3% vs. 28.6%), new ECMO (1.7% vs. 12.5%), new prone positioning cases (6.9% vs. 12.5%).
Conclusion
In adult patients with moderate-to-severe ARDS who were mechanically ventilated for < 72 hours, PHARLAP intervention was not superior to control with respect to a ventilator-free days at day 28.
Reference
Carol L Hodgson, D James Cooper, Yaseen Arabi et al. Maximal Recruitment Open Lung Ventilation in Acute Respiratory Distress Syndrome (PHARLAP). A Phase II, Multicenter Randomized Controlled Clinical Trial. Am J Respir Crit Care Med. 2019 Dec 1;200(11):1363-1372.
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