Respiratory Distress SyndromePhase 3NCT00356668
Humidified High Flow Nasal Cannula as Compared to Nasal Continuous Positive Airway Pressure
A Phase 3 study testing High Flow Nasal Cannula in people with Respiratory Distress Syndrome and Cronic Lung Disease, run by Children's Hospitals and Clinics of Minnesota at 1 site in United States.
Trial summary
The specific aims of this study are to evaluate the amount of high flow nasal cannula (HFNC) gas flow required to generate an equivalent positive distending pressure as that provided by nasal continuous positive airway pressure (NCPAP) of 6 cm H2O, assess the relationships between positive distending pressure, gas… Read more about this study
- Who is it for?
- Ages 72 hours and older
- Conditions the study is for
- Respiratory Distress Syndrome, Cronic Lung Disease
- What is being tested?
- High Flow Nasal Cannula
- Type of treatment
- Medical device
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2006to Sep 2007
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 72 hours and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 1) receiving NCPAP ventilatory support at > 72 hrs. of age and 2) requiring FiO2 21-50% on NCPAP.
Who cannot join
- FiO2 >50%, presence of pneumothorax or pleural effusion, anatomical abnormalities of the airway, lungs, or esophagus, or cyanotic congenital heart defect.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital and Clinics of Minnesota
Minneapolis, Minnesota, 55404
About this study
Official title: Observational, Cross-over Study of the Positive Distending Pressure Generated by Humidified High Flow Nasal Cannula as Compared to Nasal Continuous Positive Airway Pressure
The specific aims of this study are to evaluate the amount of high flow nasal cannula (HFNC) gas flow required to generate an equivalent positive distending pressure as that provided by nasal continuous positive airway pressure (NCPAP) of 6 cm H2O, assess the relationships between positive distending pressure, gas flow, oxygen requirement, and patient weight, and lastly, develop an appropriate protocol to be used in the NICU for transitioning patients from NCPAP to an equivalent amount of HFNC.
Read the detailed description
In the face of exogenous surfactant and use of antenatal steroids, respiratory distress syndrome (RDS) remains a leading cause of morbidity and mortality in premature infants. RDS is the result of a series of complex, interrelated events, including atelectasis, ventilation-perfusion mismatching, and lung inflammation/injury (1). The cascade of events which typifies RDS and its long-term counterpart, chronic lung disease (CLD), is rooted in the intrinsic deficits of the premature lung as well as exacerbated by mechanical ventilation, a mainstay of therapy. For this reason, scientists and clinicians alike continue to search for treatment modalities which will not only treat RDS but also decrease the incidence of chronic lung disease.
The use of non-invasive ventilatory strategies, such as nasal continuous positive airway pressure (NCPAP), in the treatment of RDS is thought to provide positive distending pressure while minimize lung inflammation and injury associated with mechanical ventilation (2). Avoidance of intubation and increased use of NCPAP to treat respiratory distress syndrome has been shown to decrease the incidence of chronic lung disease (3,4). However, NCPAP does have some common clinical limitations. First, the administration of NCPAP has inherent mechanical difficulties in appropriately maintaining the nasal prong apparatus within the small neonatal nose. Secondly, the nasal prongs used to deliver NCPAP can cause nasal septal trauma. Lastly, some premature infants do not tolerate the NCPAP apparatus which must be tightly affixed to their nose and face. This intolerance is often demonstrated by increased patient movement, and subsequently, the risk of mechanical difficulties and septal trauma increase during these times. Although NCPAP continues to be used in most neonatal intensive care units (NICUs), due to its aforementioned drawbacks, we continue to look for other effective, non-invasive modes of ventilation to provide support to premature infants with respiratory distress.
Humidified high flow nasal cannula (HFNC) has recently been introduced into neonatal respiratory care as a means of providing positive distending pressure to the neonate with respiratory distress. HFNC aims to maximize patient tolerance by employing heated, humidified gas flow through the standard neonatal nasal cannula that is used routinely in neonatal intensive care units. HFNC provides positive distending pressure by using high gas flow (>1 liter per minute) (5). Although numerous neonatal intensive care units are using HFNC, including both NICUs at Children's Hospitals of Minnesota, there are very few studies regarding its use in this population. Anecdotally, the premature babies tolerate the administration of HFNC quite well. However, like any new therapy, there are many unknowns.
There is only one study to date which investigates HFNC versus NCPAP in the preterm neonate (6). Sreenan and colleagues found HFNC to be as effective as NCPAP in the management of apnea of prematurity and also demonstrated that the positive distending pressure provided by HFNC varied with the patient's weight. Sreenan's study as well as preliminary data presented in abstract form cite HFNC use with various amounts of gas flow, ranging from 1 liter per minute up to 6 liters per minute (6,7,8). The choice of how much gas flow to use with the HFNC system is unclear. This decision is actually a three-fold question: 1) the initial amount of liter flow to use, 2) what does a particular liter flow provide for positive distending pressure to that patient, and 3) are these values system-specific? We aim to evaluate these questions in our study. Until recently, NCPAP has been the mainstay of non-invasive ventilatory support for premature babies. However, as HFNC is better tolerated and uses a nasal cannula that is less prone to mechanical mishaps than NCPAP, it is clear that we need more information to accurately treat babies with HFNC. The results of this study will help guide the use of HFNC in preterm babies with respiratory insufficiency, as knowledge of the positive distending pressures derived from the HFNC system are crucial in minimizing barotrauma to the fragile, premature lung.
- Conditions
- Respiratory Distress Syndrome, Cronic Lung Disease
- Being tested
- High Flow Nasal Cannula
- Keywords
- HFNC, NCPAP, nasal continuous positive airway pressure, humidified high flow nasal cannula, esophageal pressure, gas flow
- Medical subject headings
- Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High Flow Nasal CannulaDevice
30 minute blocks on varying flows of high flow nasal cannula
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean esophageal pressure
Measured: 3.5 hours
Secondary outcomes (1)
Vital signs
Measured: 3.5 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2006 (estimated)
- Study startJul 2006
- Study completionSep 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Respiratory Distress SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospitals and Clinics of Minnesota
- Sponsor type
- University, hospital or other
- Investigators
- Mark C Mammel, MD, Principal investigator, Children's Hospital and Clinics of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00356668
- Sponsor's protocol ID
- 0606-051
- Status last verified
- Jul 2015
- First submitted
- 24 Jul 2006
- Last updated
- 14 Jul 2015
- Results posted
- No
Publications
Fanaroff & Martin, Ch. 42, pg.1003
Jobe AH, Kramer BW, Moss TJ, Newnham JP, Ikegami M. Decreased indicators of lung injury with continuous positive expiratory pressure in preterm lambs. Pediatr Res. 2002 Sep;52(3):387-92. doi: 10.1203/00006450-200209000-00014.
PubMed 12193673Lindner W, Vossbeck S, Hummler H, Pohlandt F. Delivery room management of extremely low birth weight infants: spontaneous breathing or intubation? Pediatrics. 1999 May;103(5 Pt 1):961-7. doi: 10.1542/peds.103.5.961.
PubMed 10224173Gittermann MK, Fusch C, Gittermann AR, Regazzoni BM, Moessinger AC. Early nasal continuous positive airway pressure treatment reduces the need for intubation in very low birth weight infants. Eur J Pediatr. 1997 May;156(5):384-8. doi: 10.1007/s004310050620.
PubMed 9177982Locke RG, Wolfson MR, Shaffer TH, Rubenstein SD, Greenspan JS. Inadvertent administration of positive end-distending pressure during nasal cannula flow. Pediatrics. 1993 Jan;91(1):135-8.
PubMed 8416477Sreenan 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.
PubMed 11331690Ramanathan A, Cayabyab R, et al. High flow nasal cannula use in preterm and term newborns admitted to neonatal intensive care unit: a prospective, observational study. Pediatr Acad Soc 2005; 57:3417
Chang GY, Cox CA, Shaffer TH. Nasal cannula, CPAP, and high-flow nasal cannula: effect of flow on temperature, humidity, pressure, and resistance. Biomed Instrum Technol. 2011 Jan-Feb;45(1):69-74. doi: 10.2345/0899-8205-45.1.69.
PubMed 21322815Lampland AL, Plumm B, Meyers PA, Worwa CT, Mammel MC. Observational study of humidified high-flow nasal cannula compared with nasal continuous positive airway pressure. J Pediatr. 2009 Feb;154(2):177-82. doi: 10.1016/j.jpeds.2008.07.021. Epub 2008 Aug 30.
PubMed 18760803
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observational, Cross-over Study of the Positive Distending Pressure Generated by Humidified High Flow Nasal Cannula as Compared to Nasal Continuous Positive Airway Pressure
- ClinicalTrials.gov ID
- NCT00356668
- Acronym / sponsor ID
- 0606-051
- Conditions
- Respiratory Distress Syndrome, Cronic Lung Disease
- Keywords
- HFNC, NCPAP, nasal continuous positive airway pressure, humidified high flow nasal cannula, esophageal pressure, gas flow
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Children's Hospitals and Clinics of MinnesotaUniversity, hospital or other
- Study start
- Jul 2006
- Study completion
- Sep 2007 (actual)
- First posted
- 26 Jul 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The specific aims of this study are to evaluate the amount of high flow nasal cannula (HFNC) gas flow required to generate an equivalent positive distending pressure as that provided by nasal continuous positive airway pressure (NCPAP) of 6 cm H2O, assess the relationships between positive distending pressure, gas flow, oxygen requirement, and patient weight, and lastly, develop an appropriate protocol to be used in the NICU for transitioning patients from NCPAP to an equivalent amount of HFNC.
Detailed description
In the face of exogenous surfactant and use of antenatal steroids, respiratory distress syndrome (RDS) remains a leading cause of morbidity and mortality in premature infants. RDS is the result of a series of complex, interrelated events, including atelectasis, ventilation-perfusion mismatching, and lung inflammation/injury (1). The cascade of events which typifies RDS and its long-term counterpart, chronic lung disease (CLD), is rooted in the intrinsic deficits of the premature lung as well as exacerbated by mechanical ventilation, a mainstay of therapy. For this reason, scientists and clinicians alike continue to search for treatment modalities which will not only treat RDS but also decrease the incidence of chronic lung disease.
The use of non-invasive ventilatory strategies, such as nasal continuous positive airway pressure (NCPAP), in the treatment of RDS is thought to provide positive distending pressure while minimize lung inflammation and injury associated with mechanical ventilation (2). Avoidance of intubation and increased use of NCPAP to treat respiratory distress syndrome has been shown to decrease the incidence of chronic lung disease (3,4). However, NCPAP does have some common clinical limitations. First, the administration of NCPAP has inherent mechanical difficulties in appropriately maintaining the nasal prong apparatus within the small neonatal nose. Secondly, the nasal prongs used to deliver NCPAP can cause nasal septal trauma. Lastly, some premature infants do not tolerate the NCPAP apparatus which must be tightly affixed to their nose and face. This intolerance is often demonstrated by increased patient movement, and subsequently, the risk of mechanical difficulties and septal trauma increase during these times. Although NCPAP continues to be used in most neonatal intensive care units (NICUs), due to its aforementioned drawbacks, we continue to look for other effective, non-invasive modes of ventilation to provide support to premature infants with respiratory distress.
Humidified high flow nasal cannula (HFNC) has recently been introduced into neonatal respiratory care as a means of providing positive distending pressure to the neonate with respiratory distress. HFNC aims to maximize patient tolerance by employing heated, humidified gas flow through the standard neonatal nasal cannula that is used routinely in neonatal intensive care units. HFNC provides positive distending pressure by using high gas flow (>1 liter per minute) (5). Although numerous neonatal intensive care units are using HFNC, including both NICUs at Children's Hospitals of Minnesota, there are very few studies regarding its use in this population. Anecdotally, the premature babies tolerate the administration of HFNC quite well. However, like any new therapy, there are many unknowns.
There is only one study to date which investigates HFNC versus NCPAP in the preterm neonate (6). Sreenan and colleagues found HFNC to be as effective as NCPAP in the management of apnea of prematurity and also demonstrated that the positive distending pressure provided by HFNC varied with the patient's weight. Sreenan's study as well as preliminary data presented in abstract form cite HFNC use with various amounts of gas flow, ranging from 1 liter per minute up to 6 liters per minute (6,7,8). The choice of how much gas flow to use with the HFNC system is unclear. This decision is actually a three-fold question: 1) the initial amount of liter flow to use, 2) what does a particular liter flow provide for positive distending pressure to that patient, and 3) are these values system-specific? We aim to evaluate these questions in our study. Until recently, NCPAP has been the mainstay of non-invasive ventilatory support for premature babies. However, as HFNC is better tolerated and uses a nasal cannula that is less prone to mechanical mishaps than NCPAP, it is clear that we need more information to accurately treat babies with HFNC. The results of this study will help guide the use of HFNC in preterm babies with respiratory insufficiency, as knowledge of the positive distending pressures derived from the HFNC system are crucial in minimizing barotrauma to the fragile, premature lung.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
Who may qualify
- Ages
- 72 hours and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- 1) receiving NCPAP ventilatory support at > 72 hrs. of age and 2) requiring FiO2 21-50% on NCPAP.
Key exclusion criteria (1 listed)
- FiO2 >50%, presence of pneumothorax or pleural effusion, anatomical abnormalities of the airway, lungs, or esophagus, or cyanotic congenital heart defect.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High Flow Nasal Cannula30 minute blocks on varying flows of high flow nasal cannula | Device | – |
Primary outcome
Mean esophageal pressure
Time frame: 3.5 hours
1 secondary outcome
Vital signs
Time frame: 3.5 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2015.
- BackgroundFanaroff & Martin, Ch. 42, pg.1003
- Background: PubMed 12193673Jobe AH, Kramer BW, Moss TJ, Newnham JP, Ikegami M. Decreased indicators of lung injury with continuous positive expiratory pressure in preterm lambs. Pediatr Res. 2002 Sep;52(3):387-92. doi: 10.1203/00006450-200209000-00014.
- Background: PubMed 10224173Lindner W, Vossbeck S, Hummler H, Pohlandt F. Delivery room management of extremely low birth weight infants: spontaneous breathing or intubation? Pediatrics. 1999 May;103(5 Pt 1):961-7. doi: 10.1542/peds.103.5.961.
- Background: PubMed 9177982Gittermann MK, Fusch C, Gittermann AR, Regazzoni BM, Moessinger AC. Early nasal continuous positive airway pressure treatment reduces the need for intubation in very low birth weight infants. Eur J Pediatr. 1997 May;156(5):384-8. doi: 10.1007/s004310050620.
- Background: PubMed 8416477Locke RG, Wolfson MR, Shaffer TH, Rubenstein SD, Greenspan JS. Inadvertent administration of positive end-distending pressure during nasal cannula flow. Pediatrics. 1993 Jan;91(1):135-8.
- Background: PubMed 11331690Sreenan 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.
- BackgroundRamanathan A, Cayabyab R, et al. High flow nasal cannula use in preterm and term newborns admitted to neonatal intensive care unit: a prospective, observational study. Pediatr Acad Soc 2005; 57:3417
- Background: PubMed 21322815Chang GY, Cox CA, Shaffer TH. Nasal cannula, CPAP, and high-flow nasal cannula: effect of flow on temperature, humidity, pressure, and resistance. Biomed Instrum Technol. 2011 Jan-Feb;45(1):69-74. doi: 10.2345/0899-8205-45.1.69.
- Derived from this study: PubMed 18760803Lampland AL, Plumm B, Meyers PA, Worwa CT, Mammel MC. Observational study of humidified high-flow nasal cannula compared with nasal continuous positive airway pressure. J Pediatr. 2009 Feb;154(2):177-82. doi: 10.1016/j.jpeds.2008.07.021. Epub 2008 Aug 30.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark C Mammel, MD principal investigator
Children's Hospital and Clinics of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing High Flow Nasal Cannula in people with Respiratory Distress Syndrome and Cronic Lung Disease, run by Children's Hospitals and Clinics of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean esophageal pressure (time frame: 3.5 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00356668, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2015.