Table 2.

Randomized controlled trials evaluating LISA vs surfactant via endotracheal tube and continued mechanical ventilation.

Author/year/design	LISA group threshold/method	Control group threshold/method	Results LISA vs ETT surfactant (%, p value), aRD (95% CI)
LISA vs surfactant administration via ETT at similar FiO2 threshold as LISA arm and continued MV after surfactant administration
Kribs et al., 201528 13 centers 23–26 weeks GA Enrolled ≤2 h of life Poractant alfa,100 mg/kg No sedatives/analgesics	FiO2 >0.3, CPAP 5–8 Silverman score ≥5 4 Fr feeding tube, Cologne methoda Intubation criteria: FiO2 ≥0.45 for ≥2 h	FiO2 >0.3, CPAP ≥5–8 cm H2O Silverman score ≥5 Surfactant via ETT	n = 211 ↔ Survival without BPDc (67 vs 59%, p = 0.02d), 8.6 (–5 to 22) ↑ Survival without major complications (51 vs 36%, p = 0.02), 15 (1.4 to 28) ↓ MV during NICU stay, (75 vs 99%, p ≤ 0.001), 24 (16 to 34) ↓Pneumothorax (5 vs 12.6%, p = 0.04) ↓Grade 3–4 IVH (10 vs 22%, p = 0.02)
LISA vs continued CPAP, selective ETT intubation using either a physician-dependent criteria or criteria established a priori and continued MV
Dargaville et al., 202131 33 centers 25–28 weeks GA Enrolled ≤6 h of life Double blind Poractant alfa 200 mg/kg No sedatives and analgesics Optional atropine/sucrose	FiO2 ≥0.3, CPAP 5–8, or NIV Hobart methodb Repeat LISA not allowed Intubation criteria: FiO2 ≥0.45, persistent apnea Decision to give repeat surfactant after intubation was per physician discretion	FiO2 ≥0.3, CPAP 5–8 cm H2O or NIV Sham procedure: only gentle repositioning Intubation criteria: FiO2 ≥0.45, persistent apnea. Decision to give surfactant after intubation was per physician discretion	n = 485 ↔ Death or BPD, (44 vs 50%, p = 0.10), −6.3 (−14.2 to 1.6) ↔ Mortality (12 vs 8%, p = 0.30), 2.1 (–3.6 to −7.8) ↓ BPD (37 vs 45%, p = 0.03), −7.8 (−15 to −0.7) ↓ Pneumothorax (4.6 vs 10%, p = 0.005), −5.8 (−10.2 to −1.4) ↓ PDA medical treatment (35 vs 45%), −10.5 (−20.2 to −0.9) ↓ Intubation within 72 h of life (37 vs 72%, p ≤ 0.001), −36 (−47 to −24) ↓ Intubation during NICU stay (55 vs 81%) −27 (−40 to −13.5)
Gopel et al., 201129 12 centers 26–28 weeks GA BWT <1.5 kg, Enrolled ≤12 h of life Surfactant: not specified Optional atropine, sedatives, and analgesics	FiO2 >0.3, CPAP ≥4 cm H2O 4 Fr Feeding tube, Cologne method	Physician-dependent threshold for intubation. Surfactant per physician discretion Surfactant via ETT	n = 220 ↓ Need for MV (or if not intubated PaCO2 >65 or FiO2 >60% for ≥2 h) between 25 and 72 hc (28 vs 46%, p = 0.008), −0.18 (−0.30 to −0.05) ↓ MV during NICU stay (33 vs 73%), −0.40 (−0.52 to −0.27) ↔Air leak, BPD and mortality
Olivier et al., 201752 3 centers 32–36 weeks GA Beractant, 100 mg/kg Atropine 20 mcg/kg + fentanyl 1 mcg/kg	FiO2 ≥0.35 at CPAP 6 cm H2O 5 Fr feeding tube, Cologne method	Physician-dependent threshold for intubation. Surfactant per physician discretion Surfactant via ETT	n = 45 ↓ MV/pneumothorax requiring chest tube within 72 h of lifec (33 vs 90%, p ≤ 0.001), 0.57 (95% CI 0.54 to 0.6) ↔ Average laryngoscopy attempts (mean ± SD) 2.3 ± 1.2 vs 2.3 ± 1.9

BWT birth weight, GA gestational age, MV mechanical ventilation, PDA hemodynamically significant PDA, OR odds ratio, aRD absolute risk difference.

^aCologne method: insertion of a flexible catheter (i.e., feeding tube) below the vocal cords with direct laryngoscopy using Magill forceps.

^bHobart method: insertion of a stiff catheter (i.e., 16 G 5.25” vascular catheter) below the vocal cords with direct laryngoscopy.

^cPrimary outcome defined a priori.

^dFirst % value refers to LISA group and second value refers to control group.

↑ higher, ↓ lower, ↔Not significantly different.