Table 4:

Ongoing intervention and observational studies in PARDS

	Studytype	Participants	Intervention or assessment
Paediatric Ards Neuromuscular Blockade Study (PAN; NCT02902055)	Multicentre, double-blind, phase 4 RCT	178 patients (<5 years) with early moderate-to-severe PARDS (OI ≥12 or OSI ≥9·09)	Continuous neuromuscular blockade (rocuronium 1 mg/kg per h) vs placebo for 48 h
Real-Time Effort Driven Ventilator Management (REDvent; NCT03266016)	Single-centre, single-blind, phase 2 RCT	276 patients (>1 month to ≤18 years) with PARDS (pulmonary parenchymal disease and OI ≥4 or OSI ≥5)	Ventilator management using a CDS tool for lung and diaphragm protection vs usual care
Identifying PARDS Endotypes (NCT03539783)	Single-centre case-control study	60 patients (1 month to 18 years) admitted to the PICU: 30 intubated patients with PARDS (acute changes on chest x-ray; OI ≥4 or OSI ≥5) and 30 patients with non-lung-injury-related conditions	Bronchial epithelial cell brushing for gene-expression profiling
Long Term Follow up of Children Enrolled in the REDvent Study (NCT03709199)	Single-centre, prospective observational follow-up study	240 patients enrolled in REDvent	Ventilator management using a CDS tool for lung and diaphragm protection vs usual care
Prone and Oscillation Pediatric Clinical Trial (PROSpect; NCTO3896763)	Multicentre, open-label, 2 × 2 factorial, response-adaptive RCT	800 patients (2 weeks to 20 years) with moderate-to-severe PARDS*	CMV vs HFOV; prone vs supine positioning
Clinical Decision Support Tool in PARDS Pilot Study (NCT04068012)	Multicentre observational study	180 patients (>1 month to ≤18 years) with PARDS (pulmonary parenchymal disease and OI ≥4 or OSI ≥5)	Ventilator management using a CDS tool for lung and diaphragm protection and to guide liberation from the ventilator
Pediatric Acute Respiratory Distress Syndrome Asia Study (PARDSPROASIA; NCT04068038)	Multicentre, prospective cohort study	800 patients (≤21 years) receiving ventilatory support for PARDS*	Screening of all PICU admissions and collection of epidemiological and clinical data
Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome (LEOPARDS; NCT04113434)	Multicentre, prospective cohort study	500 patients (44 weeks to <17·5 years) with respiratory failure receiving invasive mechanical ventilation (bilateral infiltrates on chest x-ray; OI ≥4 or OSI ≥5)	Assessment of plasma protein biomarkers and peripheral blood gene expression
Infants With Severe Acute Respiratory Distress Syndrome: The Prone Trial (NCT05002478)	Single-centre, open-label RCT	14 patients (>36 weeks to <24 months) with severe PARDS (OSI ≥12·3)	Prone vs supine positioning after surfactant administration
Continuous Infusion Versus Intermittent Boluses of Cisatracurium in the Early Management of Pediatric ARDS (NCT05153525)	Single-centre, open-label, phase 4 RCT	60 patients (1 month to 18 years) with PARDS*	Intermittent boluses of cisatracurium vs intravenous infusion of cisatracurium for 24 h
ARDS in Children and ECMO Initiation Strategies Impact on Neurodevelopment (ASCEND; NCT05388708)	Multicentre, prospective cohort study (PROSpect ancillary study)	550 patients with moderate-to-severe PARDS† from the ELSO registry; 800 patients from PROSpect	ECMO vs protocolised therapies (CMV vs HFOV; prone vs supine positioning)
Endotypes in Children with Severe Acute Respiratory Distress Syndrome: Impact on Response to Treatment (ENSNARE)	Multicentre observational study (PROSpect ancillary study)	300 patients enrolled in PROSpect	Assessment of plasma protein biomarkers and wholeblood genome-wide gene expression; latent class analysis to relate expression profiles to treatment responses
Microbiome and Nutrition in Severe PARDS Trial (MANTIS)	Multicentre observational study (PROSpect ancillary study)	800 patients enrolled in PROSpect	Stool and endotracheal aspirate sampling for assessment of gut and lung microbiomes

For details of eligibility criteria, key outcomes, and study status, see appendix (pp 1–3). ARDS=acute respiratory distress syndrome. CDS=computerised decision support. CMV=conventional mechanical ventilation. ECMO=extracorporeal membrane oxygenation. ELSO=Extracorporeal Life Support Organization. HFOV high-frequency oscillatory ventilation. OI=oxygenation index. OSI=oxygen saturation index. PARDS=paediatric acute respiratory distress syndrome. PICU=paediatric intensive care unit. RCT=randomised controlled trial.

^*Defined by PALICC criteria.¹⁰

^†Defined by OI or OSI criteria in patients with bilateral lung disease on chest x-ray (one OI ≥16 or two OIs ≥12 and ≤16 at least 4 h apart, or two OSIs ≥10 at least 4 h apart, or one OI ≥12 and ≤16 and one OSI ≥10 at least 4 h apart).