Effects of Flow Magnitude on Cardiorespiratory Stability During Nasal High Flow Therapy in Preterm Infants (MASTER)

Effects of Flow Magnitude on Cardiorespiratory Stability During Nasal High Flow Therapy in Preterm Infants (MASTER Trial)

Premature babies often need help breathing for a longer period of time. Traditionally, this is done with a breathing aid called NCPAP (nasal continuous positive airway pressure). This treatment is safe and effective, but it is very time-consuming and can sometimes have side effects. In the present research project, the investigators want to find out whether another type of breathing aid called NHF (nasal high flow therapy) is just as effective for stable premature babies. The investigators suspect that NHF is just as effective, but easier to use and more comfortable.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Distress Syndrome
• Intervention / Treatment: Other: NHF high; Other: NHF low; Other: NCPAP

Detailed Description

This is a multi center parallel group three arm randomized controlled clinical trial investigating cardiorespiratory stability in stable preterm infants receiving NHF.

Currently, NCPAP remains the gold standard for administration of prolonged non-invasive ventilatory support in very preterm infants. NHF is a promising method for tailored, less invasive long-term ventilatory support for preterm infants. If ventilatory support with NHF is similarly effective to conventional NCPAP in stable preterm infants, clinicians are likely to adopt this method for widespread clinical use because of its improved comfort and potential other benefits. Primary aim of this trial is to examine cardiorespiratory stability in preterm infants treated with two commonly used NHF flowrates (Interventional group 1 and 2) in comparison to NCPAP (Comparator). Secondary aim is to examine potential comfort-related beneficial effects of NHF.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lisa Marie Bünte; Phone Number: +41 31 632 19 23; Email: lisamarie.buente@insel.ch
• Study Contact Backup: Name: André Kidszun, Prof. Dr. med.; Phone Number: +41 31 632 14 01; Email: andre.kidszun@insel.ch

Study Locations

• Germany
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • Recruiting
      • University Medical Center of the Johannes Gutenberg-University Mainz
      • Contact: Susanne Tippmann, Dr. med.; Phone Number: +49 6131 17 5892; Email: Susanne.Tippmann@unimedizin-mainz.de
      • Principal Investigator: Susanne Tippmann, Dr. med.
• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • Department of Pediatrics, Inselspital
    • Contact: Lisa M Bünte; Phone Number: +41316321923; Email: lisamarie.buente@insel.ch
    • Sub-Investigator: Lisa M Bünte
    • Sub-Investigator: Bubl Benedikt, Dr. med.
    • Contact: André Kidszun, Prof. Dr. med.; Phone Number: +41 31 632 14 01; Email: andre.kidszun@insel.ch
    • Principal Investigator: André Kidszun, Prof. Dr. med.
    • Sub-Investigator: Thomas Riedel, Prof. Dr. med.
    • Sub-Investigator: Thomas Riva, Prof. Dr. med.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Inclusion if all apply.

• Preterm infants up to 31+6 weeks GA admitted to the Division of Neonatology at Inselspital Bern, Switzerland or Division of Neonatology at the University Medical Center of the Johannes Gutenberg-University Mainz, Germany (inborn or outborn)
• >2nd day of life (defined as date day)

• Stable on NCPAP 6 cm H2O for ≥ 24 hours, defined as:

  • ≤ 2 apneas with concomitant bradycardias (<100/min) per hour for the previous 6 hours
  • FiO2 ≤ 0.3 and not increasing
  • No significant chest recessions (Silverman Score < 5)
  • Respiratory rate ≤ 60/min
  • No need for intermittent positive pressure ventilation
• Parents with an age 18+ years
• Written parental informed consent (or other legal representative)

Exclusion Criteria:

Exclusion if any applies.

• Significant fetal anomalies
• Primary palliative care
• Stable on NCPAP 6 cm H2O according to stability criteria for more than 120 hours

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NHF high; Nasal high flow therapy 8L/min	Other: NHF high; Nasal high flow therapy 8L/min.
Experimental: NHF low; Nasal high flow therapy 6L/min	Other: NHF low; Nasal high flow therapy 6L/min.
Active Comparator: NCPAP; Nasal continuous positive airway pressure 6 cm H20	Other: NCPAP; Nasal continuous positive airway pressure 6 cm H20

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment failure	Treatment failure is a composite outcome defined as meeting one of the following treatment failure criteria within 24 hours of starting of intervention: >2 apneas with concomitant bradycardias (<100/min) per hour for > 1 hour or; FiO2 > 0.3 consistently for > 1 hour or; Significant chest recessions (Silverman Score ≥ 5) for > 1 hour or; Respiratory rate > 60/min consistently for > 1 hour or; Any need for intermittent positive pressure ventilation The presence of "Treatment failure" within 24 hours of starting of intervention will be documented (dichotomous outcome; yes/no).	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apneas and bradycardias	The total frequency of apneas and bradycardias (<100/min) within 24 hours of starting of intervention will be documented.	24 hours
Respiratory rate (RR)	The mean RR within 24 hours of starting of intervention will be documented.	24 hours
Heart rate (HR)	The mean HR within 24 hours of starting of intervention will be documented.	24 hours
Oxygen saturation (SpO2) and fraction of inspired oxygen (FiO2)	The mean SpO2/FiO2 ratio within 24 hours of starting of intervention will be documented.	24 hours
Frequency of any treatment failure	Treatment failure is a composite outcome (see "Outcome 1"). The frequency of any treatment failure during the duration of the study will be documented.	Individual study duration: estimated to be between a minimum of 7 days to an (estimated) maximum of 10 weeks.
Rescue NCPAP	Rescue NCPAP is defined as NCPAP >6 cm H2O. The frequency of need for Rescue NCPAP during the duration of the study will be collected.	Individual study duration: estimated to be between 7 days to 10 weeks.
Postmenstrual age (PMA) off positive pressure support	The investigators will document the PMA when the infant is off positive pressure support.	Estimated to be at a PMA of approximately 29 to 34 weeks.
Postmenstrual age (PMA) off FiO2 > 0.21	The investigators will document the PMA when the infant is off FiO2 > 0.21	Estimated to be at a PMA between approximately 28 to 34 weeks.
Postmenstrual age (PMA) at discharge	The investigators will document the PMA when the infant is being discharged from the hospital.	Estimated to be at a PMA of approximately 38-40 weeks.
Cerebral oxygen saturation (cRSO2) 1 hour before until 3 hours after start of the intervention	The cerebral oxygen saturation (cRSO2) in [%] 1 hour before until 3 hours after start of the intervention will be measured by using Near-infrared spectroscopy (NIRS).	4 hours
Time spent <55% cRSO2 1 hour before until 3 hours after start of the intervention	The time spent <55% cRSO2 in [min] 1 hour before until 3 hours after start of the intervention will be measured by using Near-infrared spectroscopy (NIRS).	4 hours
Cerebral oxygen saturation (cRSO2) 1 hour before until 3 hours after cessation of the intervention	The cerebral oxygen saturation (cRSO2) in [%] 1 hour before until 3 hours after cessation of the intervention will be measured by using Near-infrared spectroscopy (NIRS).	4 hours
Time spent <55% cRSO2 1 hour before until 3 hours after cessation of the intervention	The time spent <55% cRSO2 in [min] 1 hour before until 3 hours after cessation of the intervention will be measured by using Near-infrared spectroscopy (NIRS).	4 hours
Incidence of Bronchopulmonary dysplasia (BPD)	The incidence with specification of severity of BPD at 36 weeks PMA will be documented. BPD is a form of chronic lung disease (CLD). BPD is classified into 3 levels of severity according to the internationally used definition of Jobe and Bancalari (1). FiO2 >0.21 for ≥ 28 days and; Breathing room air (mild); FiO2 <0.3 (moderate); FiO2 ≥ 0.3 and/or positive pressure support (severe) (1) Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163(7):1723-9.	At 36 weeks PMA
Urinary cortisol	A 24-hour-urine-sample will be collected on the third study day. The urinary production rates of cortisol and the most important metabolites will be documented as an indicator for infant stress.	24 hours
COMFORTneo score	The COMFORTneo score will be documented on the third, fourth and fifth study day. The score measures comfort and chronic pain by observation.	72 hours
Revised Bernese Pain Scale for Neonates (BSN-R) score	The BSN-R score will be documented on the third, fourth and fifth study day. The score measures pain.	72 hours
Parental assessment of comfort	The parents will be asked 3 predefined questions concerning their infants' comfort on the on the third, fourth and fifth study day.	72 hours
NASA Task Load Index (NASA-TLX)	The NASA-TLX will be filled out by the participants' nurses on the third, fourth and fifth study day. The NASA-TLX is a questionnaire that measures workload.	72 hours
Behavioral Sleep stage classification for Preterm Infants (BeSSPI)	Sleep-wake cycles as determined by the BeSSPI on the fourth study day will be documented. The BeSSPI identifies sleep stages by observation and takes approximately 2.5 hours.	24 hours
Parental Bonding Questionnaire (PBQ)	The score of the PBQ will be documented at 36 weeks PMA. The PBQ investigates infant-parental bonding.	At 36 weeks PMA
Age at initiating breastfeeds	The postmenstrual age (PMA) at initiating breastfeeds will be documented. This refers to the PMA at which the first successful breastfeeding attempt takes place.	Estimated to be between 30-34 weeks PMA.
Age at reaching full breastfeeds	The postmenstrual age (PMA) at reaching full breastfeeds will be documented. This corresponds to 100% nutrition per breastfeeds for 24 consecutive hours.	Estimated to be between 34-40 weeks PMA.
Weight	The weight in [g] at 36 weeks postmenstrual age (PMA) will be documented.	At 36 weeks PMA
Head circumference	The head circumference in [cm] at 36 weeks postmenstrual age (PMA) will be documented.	At 36 weeks PMA
Change in end-expiratory lung impedance (ΔEELI)	The change Δ in end-expiratory lung impedance (ΔEELI) will be measured using electrical impedance tomography (EIT) at 9 different timepoints during the first 48 hours after starting of intervention. One measurement will last 6 minutes. The measurements will take place: within 30 minutes before starting of intervention (baseline measurement); 3 minutes before until 3 minutes after starting of intervention; within 30 minutes after starting of intervention; 2, 6, 12, 24, 36, and 48 hours after starting of intervention	48 hours
Change in global inhomogeneity (ΔGI) index	The change Δ in global inhomogeneity (ΔGI) index will be measured using electrical impedance tomography (EIT) at 9 different timepoints during the first 48 hours after starting of intervention. One measurement will last 6 minutes. The measurements will take place: within 30 minutes before starting of intervention (baseline measurement); 3 minutes before until 3 minutes after starting of intervention; within 30 minutes after starting of intervention; 2, 6, 12, 24, 36, and 48 hours after starting of intervention	48 hours
Change in variability of tidal volume (ΔTV)	The change Δ in variability of tidal volume (ΔTV) will be measured using electrical impedance tomography (EIT) at 9 different timepoints during the first 48 hours after starting of intervention. One measurement will last 6 minutes. The measurements will take place: within 30 minutes before starting of intervention (baseline measurement); 3 minutes before until 3 minutes after starting of intervention; within 30 minutes after starting of intervention; 2, 6, 12, 24, 36, and 48 hours after starting of intervention	48 hours
Change in ratio of tidal volume anterior/posterior (ΔRatio TV ap)	The change Δ in ratio of tidal volume anterior/posterior (ΔRatio TV ap) will be measured using electrical impedance tomography (EIT) at 9 different timepoints during the first 48 hours after starting of intervention. One measurement will last 6 minutes. The measurements will take place: within 30 minutes before starting of intervention (baseline measurement); 3 minutes before until 3 minutes after starting of intervention; within 30 minutes after starting of intervention; 2, 6, 12, 24, 36, and 48 hours after starting of intervention	48 hours
Nasal trauma score	The nasal trauma score is assessed according to internal standard guidelines in case of a present nasal trauma. The highest respective score and time of assessment will be documented on the participant CRF at 36 weeks PMA. Measuring nasal trauma using the Nasal trauma score takes approximately 20 seconds.	Individual study duration: estimated to be between 7 days to 10 weeks.

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Investigators: Principal Investigator: André Kidszun, Prof. Dr. med., Division of Neonatology, Department of Pediatrics, Inselspital

Publications and helpful links

General Publications

• Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001 Jun;163(7):1723-9. doi: 10.1164/ajrccm.163.7.2011060. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: May 30, 2023
• First Submitted That Met QC Criteria: June 8, 2023
• First Posted (Actual): June 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 19, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Continuous positive airway pressure; Nasal high flow therapy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn
• Other Study ID Numbers: 2022-02287

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No