Comparison of Humidified High Flow Nasal Cannula to Nasal CPAP in Neonates

Respiratory Insufficiency Clinical Trial

— HHFNC  

Official title:

Comparison of Humidified High Flow Nasal Cannula to Nasal Continuous Positive Airway Pressure for Non-Invasive Respiratory Support in Neonates

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00609882
• Other study ID #: 24721
• Secondary ID: UofU_IRB_0002472
• Status: Completed
• Phase: N/A
• First received: January 24, 2008
• Last updated: February 5, 2013
• Start date: December 2007
• Est. completion date: June 2012

Study information

• Verified date: February 2013
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

We hypothesize that the success rate for keeping babies extubated (without a breathing tube for assisted mechanical ventilation), defined as the proportion of infants remaining extubated for a minimum of 72 hours, will be equivalent among infants managed with nasal CPAP compared to humidified high flow nasal cannula (HHFNC).

Description:

Respiratory failure remains a common problem in the neonatal ICU. Among premature infants with respiratory failure the use of mechanical ventilation has been associated with increased risk for secondary lung injury and subsequent development of bronchopulmonary dysplasia (BPD). As reported by Avery et al and Van Marter et al, early application of nasal continuous positive airway pressure (nCPAP) has been shown as an effective non-invasive mode of respiratory support in this population.(1, 2) Additionally, in the premature sheep and baboon models of BPD, the early use of nCPAP is accompanied by significant improvement in subsequent lung development and alveolization.(3) In light of these findings, there has been a concerted effort in most NICU's to avoid prolonged ventilator support through the early application of nCPAP.

Unfortunately, nCPAP systems are not always easily applied or tolerated in the preterm population.

Difficulties with the application of nCPAP include bulky head wraps, positional problems, compression of the nose, marked dilation and tissue breakdown of the nares, and apparent agitation, often leading to the use of potentially neurotoxic medications.(4) Previous studies have suggested that NC flows at 1-2 lpm may also generate a positive pressure in the airway of preterm infants.(5) The use of NC flow to generate positive airway pressure would minimize many of the application issues of nCPAP. However, standard NC systems used in neonates routinely employ gas that is inadequately warmed and humidified, limiting the use of such flows due to increased risk of nasal mucosa injury, and possibly increasing the risk for nosocomial infection.(4, 6) The development of humidified high flow via nasal cannulas (HHFNC) systems may obviate these problems and provide a safe, effective alternative to nCPAP in the preterm infant. Unfortunately, HHFNC does not allow the measurement of distending pressure without an invasive process such as an esophageal pressure catheter. Two recent reports have suggested that HHFNC does not provide excessive distending pressure.(7, 8) The study by Saslow and colleagues found that work of breathing and lung compliance were improved in preterm infants on HHFNC up to a maximum of 5 lpm compared to nCPAP at 6 cm H2O.(7) In comparison to nCPAP, the maximum positive distending pressure measured was 4.8 cm H2O and was not significantly increased with HHFNC flows up to 5 lpm. Kubicka and colleagues also demonstrated that the maximum distending pressure measured during support with HHFNC up to 8 lpm was < 5 cm H2O.(8)

A recent publication has suggested that HHFNC can safely and effectively be applied in the non-invasive respiratory management of premature infants with respiratory dysfunction.(9) In this retrospective analysis evaluating over 1000 infants, Shoemaker et al reported a significant decrease in ventilator days among the group of infants managed with HHFNC compared to infants previously managed with nCPAP. Additionally, they found no increased adverse effects noted such as air leak, intraventricular hemorrhage, nosocomial infection or BPD. In a smaller prospective study, Campbell et al did not find a benefit from high-flow NC among a group 40 infants < 1250 grams.(10) However, they did not use adequate humidification and the maximum "high-flow" applied was < 2 lpm. The previously noted study by Woodhead et al demonstrated that HHFNC decreased respiratory work effort and was more effective at preventing reintubation than high-flow from a standard, non-heated, non-humidified nasal cannula.(4)

Thus HHFNC, with flow rates as high as 8 lpm, is being used clinically in a large number of NICU's, including all of the units participating in this study, for management of a variety of neonatal respiratory problems. The introduction of HHFNC into clinical practice has not been accompanied by apparent changes in neonatal outcome, but this has not been systematically studied in a randomized, controlled approach.

The purpose of this randomized controlled trial is to evaluate the clinical impact of applying HHFNC to that of nCPAP among a group of infants requiring continuing non-invasive respiratory support in the NICU.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 420
• Est. completion date: June 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 8 Weeks

Eligibility

Inclusion Criteria:

1. Birth weight > 1000 grams and > 27 weeks gestation

2. Candidate for non-invasive respiratory support as a result of:

1. an intention to manage the infant with non-invasive (no endotracheal tube) respiratory support from birth initiated in the first 24 hours of life

2. an intention to extubate an infant being managed with intubated respiratory support to non-invasive support

Exclusion Criteria:

1. Birth weight < 1000 grams

2. Estimated gestation < 29 weeks

3. Participation in a concurrent study that prohibits the use of HHFNC

4. Active air leak syndrome

5. Infants with abnormalities of the upper and lower airways; such as Pierre- Robin, Treacher-Collins, Goldenhar, choanal atresia or stenosis, cleft lip and/or palate, or

6. Infants with significant abdominal or respiratory malformations including tracheo-esophageal fistula, intestinal atresia, omphalocele, gastroschisis, and congenital diaphragmatic hernia.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pulmonary Valve Insufficiency
• Respiratory Insufficiency

Intervention

Other:
• Nasal CPAP
Infants randomized to the Standard nasal CPAP via "bubble" or ventilator support at levels of 4-8 cm H2O post extubation
• Humidified High Flow Nasal Cannula (HHFNC)
HHFNC

Locations

Country	Name	City	State
China	Hebei Provincial Children's Hospital	Shijiazhuang 050031
United States	Wilford Hall Medical Center	Lackland AFB	Texas
United States	McKay-Dee Medical Center	Ogden	Utah
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Intermountain Medical Center	Salt Lake City	Utah
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	University Hospital	Salt Lake City	Utah
United States	Dixie Medical Center	St. George	Utah

Sponsors (2)

Lead Sponsor	Collaborator
University of Utah	Intermountain Health Care, Inc.

Countries where clinical trial is conducted

United States,  China, 

References & Publications (10)

Avery ME, Tooley WH, Keller JB, Hurd SS, Bryan MH, Cotton RB, Epstein MF, Fitzhardinge PM, Hansen CB, Hansen TN, et al. Is chronic lung disease in low birth weight infants preventable? A survey of eight centers. Pediatrics. 1987 Jan;79(1):26-30. — View Citation

Campbell DM, Shah PS, Shah V, Kelly EN. Nasal continuous positive airway pressure from high flow cannula versus Infant Flow for Preterm infants. J Perinatol. 2006 Sep;26(9):546-9. Epub 2006 Jul 13. — View Citation

Kopelman AE, Holbert D. Use of oxygen cannulas in extremely low birthweight infants is associated with mucosal trauma and bleeding, and possibly with coagulase-negative staphylococcal sepsis. J Perinatol. 2003 Mar;23(2):94-7. — View Citation

Kubicka ZJ, Limauro J, Darnall RA. Heated, humidified high-flow nasal cannula therapy: yet another way to deliver continuous positive airway pressure? Pediatrics. 2008 Jan;121(1):82-8. doi: 10.1542/peds.2007-0957. — View Citation

Saslow JG, Aghai ZH, Nakhla TA, Hart JJ, Lawrysh R, Stahl GE, Pyon KH. Work of breathing using high-flow nasal cannula in preterm infants. J Perinatol. 2006 Aug;26(8):476-80. Epub 2006 May 11. — View Citation

Shoemaker MT, Pierce MR, Yoder BA, DiGeronimo RJ. High flow nasal cannula versus nasal CPAP for neonatal respiratory disease: a retrospective study. J Perinatol. 2007 Feb;27(2):85-91. — View Citation

Sreenan C, Lemke RP, Hudson-Mason A, Osiovich H. High-flow nasal cannulae in the management of apnea of prematurity: a comparison with conventional nasal continuous positive airway pressure. Pediatrics. 2001 May;107(5):1081-3. — View Citation

Thomson MA, Yoder BA, Winter VT, Martin H, Catland D, Siler-Khodr TM, Coalson JJ. Treatment of immature baboons for 28 days with early nasal continuous positive airway pressure. Am J Respir Crit Care Med. 2004 May 1;169(9):1054-62. Epub 2004 Feb 12. — View Citation

Van Marter LJ, Allred EN, Pagano M, Sanocka U, Parad R, Moore M, Susser M, Paneth N, Leviton A. Do clinical markers of barotrauma and oxygen toxicity explain interhospital variation in rates of chronic lung disease? The Neonatology Committee for the Developmental Network. Pediatrics. 2000 Jun;105(6):1194-201. — View Citation

Woodhead DD, Lambert DK, Clark JM, Christensen RD. Comparing two methods of delivering high-flow gas therapy by nasal cannula following endotracheal extubation: a prospective, randomized, masked, crossover trial. J Perinatol. 2006 Aug;26(8):481-5. Epub 2006 May 25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare extubation success rate, defined as % infants remaining extubated for > 72 hrs, among infants managed with HHFNC versus nCPAP		72 hrs	No
Secondary	Compare frequency of significant apnea after extubation to HHFNC v CPAP		7 days	Yes
Secondary	Compare total duration of ventilator, positive pressure (CPAP and/or HHFNC), and oxygen use up to the time of discharge from the NICU		3 months	No
Secondary	Compare incidence of potential adverse effects associated with the use of nasal CPAP and HHFNC including pulmonary air leaks, nasal deformities, feeding intolerance, necrotizing enterocolitis, intestinal perforation and BPD		3 months	Yes
Secondary	Compare weight gain and the time to establish full enteral feeds (> 120 ml/kg/d) between infants on HHFNC v CPAP		3 months	No