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Randomized Controlled Trial
. 2025 Jun;60(6):e71167.
doi: 10.1002/ppul.71167.

HHHFNC Versus NIPPV Delivered by Long Narrow Cannula in Preterm Infants: Randomized Noninferiority Trial

Ayala Gover  1   2 , Tatiana Smolkin  3   4 , Michal Molad  2   5 , Karen Lavie-Nevo  2   5 , Adir Iofe  1   2 , Rasha Zoabi-Safadi  1   2 , Arina Toropine  1   2 , Rawnak Nazem Saab  3   4 , Dan Waisman  2   5 , Avi Rotschild  2   5 , Amir Kugelman  2   6 , Arieh Riskin  1   2
Affiliations
Randomized Controlled Trial

HHHFNC Versus NIPPV Delivered by Long Narrow Cannula in Preterm Infants: Randomized Noninferiority Trial

Ayala Gover et al. Pediatr Pulmonol. 2025 Jun.

Abstract

Background: Heated humidified high flow (HHHFNC) and nasal intermittent positive pressure ventilation (NIPPV) delivered by cannula with long and narrow tubing (CLNT) are increasingly used in preterm infants for providing noninvasive respiratory support, due to their high comfort level and minimal nasal trauma. Despite their widespread use, no randomized controlled trial has been conducted so far.

Objective: Determine whether HHHFNC is non-inferior to CLNT-NIPPV in providing respiratory support for preterm infants.

Study design: An unblinded, randomized controlled, non-inferiority multicenter trial.

Methodology: Preterm infants randomized to either HHHFNC or CLNT-NIPPV. Infants born > 28 weeks of gestation were eligible to enter the study either as primary treatment after birth or post-extubation. Infants born ≤ 28 weeks of gestation were only eligible post-extubation. The primary outcome was treatment failure within 7 days.

Results: One hundred and thirty infants were enrolled in the study; 65 in each group. Most (82%) were > 28 weeks, and primary treatment (73%). HHHFNC was non-inferior to CLNT-NIPPV in the primary outcome which occurred in 12.3% compared to 23.0% of the infants, respectively (risk difference (RD) -10.77%, 95% CI of RD -23.7 to 2.22 [within the non-inferiority margin], χ2p = 0.168). HHHFNC was associated with significantly less nasal trauma compared to CLNT-NIPPV but with longer time on the allocated respiratory support. No significant differences were found between the groups in secondary respiratory and neonatal outcomes.

Conclusions: In this study of preterm infants mostly > 28 weeks of gestation, HHHFNC was non-inferior to CLNT-NIPPV in providing respiratory support, and caused less nasal trauma.

Keywords: newborn; noninvasive respiratory support; respiratory therapy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The CONSORT flow diagram.
Figure 2
Figure 2
Non‐inferiority trial results. (A) Possible scenarios of results for a non‐inferiority trial according to Piaggio et al. (B) Results of this study concerning the primary outcome, treatment failure within 7 days. Error bars indicate 95% CI of the risk difference between using HHHFNC and CLNT‐NIPPV. CLNT‐NIPPV, nasal intermittent positive pressure ventilation delivered by cannula with long and narrow tubing; HHHFNC, heated humidified high flow nasal cannula. a The study was underpowered to establish non‐inferiority in this subgroup.
See this image and copyright information in PMC

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