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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01962818




Registration number
NCT01962818
Ethics application status
Date submitted
9/10/2013
Date registered
14/10/2013
Date last updated
22/03/2023

Titles & IDs
Public title
High Frequency Oscillatory Ventilation Combined With Intermittent Sigh Breaths: Effects on Lung Volume Monitored by Electric Tomography Impedance.
Scientific title
High Frequency Oscillatory Ventilation Combined With Intermittent Sigh Breaths in Neonates Compared With Standard High Frequency Oscillatory Ventilation - Effects on Lung Volume Monitored by Electric Tomography Impedance
Secondary ID [1] 0 0
1936M
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Respiratory Distress Syndrome In Premature Infants 0 0
Bronchopulmonary Dysplasia 0 0
Ventilator-Induced Lung Injury 0 0
Functional Residual Capacity 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Reproductive Health and Childbirth 0 0 0 0
Complications of newborn
Injuries and Accidents 0 0 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - HFOV combined with sigh breaths

Experimental: HFOV-sigh at start - Each patient will be exposed to either HFOV alone (HFOV-only) or HFOV combined with sigh breaths (HFOV-sigh), but in different order.

MAP=mean airway pressure.

DURING HFOV-SIGH:

Frequency 3 breaths/min Ti = 1s Peak inspiratory pressure (PIP) = 30 cm H2O

For patients already on HFOV-sigh at study start:

• MAP-set will be left unchanged at pre-trial settings.

For patients on HFOV-only at study start:

• During periods with superimposed sigh breaths, MAP-set will be reduced in accordance with a calculation of MAP aiming to keep average mean airway-pressure (MAP) unchanged. (MAP=(PIP\*Tinsp+PEEP\*Texp)/(Tinsp+Texp)

DURING HFOV-ONLY

For patients on HFOV-sigh at study start:

• During HFOV-only, the MAP-set will be increased in accordance with a calculation of MAP, aiming to keep average mean airway-pressure (MAP) unchanged.

For patients on HFOV-only at study start:

• MAP-set will be left unchanged at pre-trial settings.

Experimental: HFOV-only at start - Each patient will be exposed to either HFOV alone (HFOV-only) or HFOV combined with sigh breaths (HFOV-sigh), but in different order.

MAP=mean airway pressure.

DURING HFOV-SIGH:

Frequency 3 breaths/min Ti = 1s Peak inspiratory pressure (PIP) = 30 cm H2O

For patients already on HFOV-sigh at study start:

• MAP-set will be left unchanged at pre-trial settings.

For patients on HFOV-only at study start:

• During periods with superimposed sigh breaths, MAP-set will be reduced in accordance with a calculation of MAP aiming to keep average mean airway-pressure (MAP) unchanged. (MAP=(PIP\*Tinsp+PEEP\*Texp)/(Tinsp+Texp)

DURING HFOV-ONLY

For patients on HFOV-sigh at study start:

• During HFOV-only, the MAP-set will be increased in accordance with a calculation of MAP, aiming to keep average mean airway-pressure (MAP) unchanged.

For patients on HFOV-only at study start:

• MAP-set will be left unchanged at pre-trial settings.


Other interventions: HFOV combined with sigh breaths
It is planned only to investigate infants already ventilated on the HFOV-modus on high frequency oscillators, where the HFOV modus can be superimposed on conventional modes of ventilation. This gives the opportunity to combine HFOV with intermittent sigh breaths with a pre-set frequency and pre-set peak inspiratory pressure (PIP) and thus comparing HFOV combined with sigh breaths (HFOV-sigh) with conventional HFOV (HFOV-only).

All included participants will be exposed to the two different ventilator strategies tested in this trial, albeit in alternating and different order.

Each patient will serve, as it's own control. The trial will involve four alternating 1-hours periods allowing a sufficient "wash-out" period, as it has been shown that alveolar recruitment and derecruitment may take up to 25 min after changes to ventilator pressures At study start the patients will randomly be assigned to either starting with HFOV-only or HFOV-sigh
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Global changes in end expiratory lung volume (EELV)
Timepoint [1] 0 0
all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Primary outcome [2] 0 0
Regional ventilation distribution
Timepoint [2] 0 0
all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Secondary outcome [1] 0 0
Global changes in oscillatory volume (Vosv):
Timepoint [1] 0 0
all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Secondary outcome [2] 0 0
Regional difference in oscillatory volume
Timepoint [2] 0 0
all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Secondary outcome [3] 0 0
Regional distribution of sigh-breaths volume
Timepoint [3] 0 0
all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Secondary outcome [4] 0 0
Global inhomogeneity index
Timepoint [4] 0 0
all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Secondary outcome [5] 0 0
Phase angle analyses
Timepoint [5] 0 0
all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Secondary outcome [6] 0 0
vital parameters during HFOV-sigh vs HFOV-only
Timepoint [6] 0 0
all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.

Eligibility
Key inclusion criteria
* Infants at 24-36 weeks corrected gestational age
* Already ventilated with high frequency ventilation
* Requiring FiO2=21%-70% to maintain adequate oxygen saturation.
* Clinical stable

o i.e. ventilated on current settings for more than just a few hours with stable but not necessarily normalized blood gases or transcutaneous values and oxygen requirement.
* Parent(s) or guardian able and willing to provide informed consent
Minimum age
24 Weeks
Maximum age
44 Weeks
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Major congenital cardiovascular or respiratory abnormalities (excluding Patent ductus arteriosus).

* Poor skin integrity precluding use of adhesive ECG electrodes used for EIT monitoring.
* The physician responsible for the baby considers one of the ventilation modes unsuitable for the infant or the patient unsuitable for EIT monitoring.
* Lack of parental signed written informed consent or if both parents are under 18 years of age (due to complexities of obtaining consent).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2023
Sample size
Target
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Department of Neonatology, Mater Mothers Hospital - Brisbane
Recruitment postcode(s) [1] 0 0
4101 - Brisbane

Funding & Sponsors
Primary sponsor type
Other
Name
Rigshospitalet, Denmark
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Background Ventilator induced lung injury (VILI) remains a problem in neonatology. High frequency oscillatory ventilation (HFOV) provides effective gas exchange with minimal pressure fluctuation around a continuous distending pressure and therefore small tidal volume. Animal studies showed that recruitment and maintenance of functional residual capacity (FRC) during HFOV ("open lung concept") could reduce lung injury.

"Open lung HFOV" is achieved by delivering a moderate high mean airway pressure (MAP) using oxygenation as a guide of lung recruitment. Some neonatologists suggest combining HFOV with recurrent sigh-breaths (HFOV-sigh) delivered as modified conventional ventilator-breaths at a rate of 3/min. The clinical observation is that HFOV-sigh leads to more stable oxygenation, quicker weaning and shorter ventilation. This may be related to improved lung recruitment.

Electric Impedance Tomography (EIT) enables measurement and mapping of regional ventilation distribution and end-expiratory lung volume (EELV). EIT generates cross-sectional images of the subject based on measurement of surface electrical potentials resulting from an excitation with small electrical currents and has been shown to be a valid and safe tool in neonates.

Purpose, aims:

* To compare HFOV-sigh with HFOV-only and determine if there is a difference in global and regional EELV (primary endpoints) and spatial distribution of ventilation measured by EIT
* To provide information on feasibility and treatment effect of HFOV-sigh to assist planning larger studies. We hypothesize that EELV during HFOV-sigh is higher, and that regional ventilation distribution is more homogenous.

Methods:

Infants at 24-36 weeks corrected gestational age already on HFOV are eligible. Patients will be randomly assigned to HFOV-sigh (3 breaths/min) followed by HFOV-only or vice versa for 4 alternating 1-hours periods (2-treatment, double crossover design, each patient being its own control). During HFOV-sigh set-pressure will be reduced to keep MAP constant, otherwise HFOV will remain at pretrial settings.

16 ECG-electrodes for EIT recording will be placed around the chest at study start. Each recording will last 180s, and will be done at baseline and at 30 and 50 minutes after each change in ventilator modus.

Feasibility No information of EIT-measured EELV in babies on HFOV-sigh exists. This study is a pilot-trial.

In a similar study-protocol of lung recruitment during HFOV-sigh using "a/A-ratio" as outcome, 16 patients was estimated to be sufficient to show an improvement by 25%. This assumption was based on clinical experience in a unit using HFOV-sigh routinely. As the present study examines the same intervention we assume that N=16 patients will be a sufficient sample size. We estimate to include this number in 6 months.
Trial website
https://clinicaltrials.gov/study/NCT01962818
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Christian Heiring, neonatologist
Address 0 0
Department of Neonatology, Rigshospitalet, Copenhagen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01962818