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

NCT ID: NCT00609882

Last Updated: 2013-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 420 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2012-06-30

Brief 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).

Detailed 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.

Conditions

Respiratory Insufficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HHFNC

Infants randomized to the Humidified High Flow Nasal Cannula (HHFNC) treatment group post extubation

Group Type: ACTIVE_COMPARATOR

Nasal CPAP

Intervention Type: OTHER

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)

Intervention Type: OTHER

HHFNC

nCPAP

Infants randomized to the nasal Continuous Positive Airway Pressure (nCPAP) treatment group

Group Type: ACTIVE_COMPARATOR

Nasal CPAP

Intervention Type: OTHER

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)

Intervention Type: OTHER

HHFNC

Interventions

Nasal CPAP

Infants randomized to the Standard nasal CPAP via "bubble" or ventilator support at levels of 4-8 cm H2O post extubation

Intervention Type: OTHER

Humidified High Flow Nasal Cannula (HHFNC)

HHFNC

Intervention Type: OTHER

Eligibility Criteria

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.

• Maximum Eligible Age: 8 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Intermountain Health Care, Inc.

OTHER

Sponsor Role: collaborator

University of Utah

OTHER

Sponsor Role: lead

Responsible Party

University of Utah School of Medicine

Principal Investigators

Bradley A Yoder, MD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Wilford Hall Medical Center

Lackland Air Force Base, Texas, United States

McKay-Dee Medical Center

Ogden, Utah, United States

Utah Valley Regional Medical Center

Provo, Utah, United States

Primary Children's Medical Center

Salt Lake City, Utah, United States

University Hospital

Salt Lake City, Utah, United States

Intermountain Medical Center

Salt Lake City, Utah, United States

Dixie Medical Center

St. George, Utah, United States

Hebei Provincial Children's Hospital

Shijiazhuang, , China

Countries

United States; China

References

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.

Reference Type: BACKGROUND

PMID: 3797169 (View on PubMed)

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. doi: 10.1542/peds.105.6.1194.

Reference Type: BACKGROUND

PMID: 10835057 (View on PubMed)

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. doi: 10.1164/rccm.200309-1276OC. Epub 2004 Feb 12.

Reference Type: BACKGROUND

PMID: 14962819 (View on PubMed)

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. doi: 10.1038/sj.jp.7211543. Epub 2006 May 25.

Reference Type: BACKGROUND

PMID: 16724119 (View on PubMed)

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. doi: 10.1542/peds.107.5.1081.

Reference Type: BACKGROUND

PMID: 11331690 (View on PubMed)

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. doi: 10.1038/sj.jp.7210865.

Reference Type: BACKGROUND

PMID: 12673256 (View on PubMed)

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. doi: 10.1038/sj.jp.7211530. Epub 2006 May 11.

Reference Type: BACKGROUND

PMID: 16688202 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18166560 (View on PubMed)

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. doi: 10.1038/sj.jp.7211647.

Reference Type: BACKGROUND

PMID: 17262040 (View on PubMed)

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. doi: 10.1038/sj.jp.7211561. Epub 2006 Jul 13.

Reference Type: BACKGROUND

PMID: 16837929 (View on PubMed)

Yoder BA, Stoddard RA, Li M, King J, Dirnberger DR, Abbasi S. Heated, humidified high-flow nasal cannula versus nasal CPAP for respiratory support in neonates. Pediatrics. 2013 May;131(5):e1482-90. doi: 10.1542/peds.2012-2742. Epub 2013 Apr 22.

Reference Type: DERIVED

PMID: 23610207 (View on PubMed)

Other Identifiers

UofU_IRB_00024721

Identifier Type: -

Identifier Source: secondary_id

24721

Identifier Type: -

Identifier Source: org_study_id