High Frequency Oscillatory Ventilation Combined With Intermittent Sigh Breaths: Effects on Lung Volume Monitored by Electric Tomography Impedance.

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified October 2013 by Rigshospitalet, Denmark
Sponsor:
Information provided by (Responsible Party):
Christian Heiring, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT01962818
First received: October 9, 2013
Last updated: October 10, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention
Respiratory Distress Syndrome In Premature Infants
Bronchopulmonary Dysplasia
Ventilator-Induced Lung Injury
Functional Residual Capacity
Other: HFOV combined with sigh breaths

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • Global changes in end expiratory lung volume (EELV) [ Time Frame: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day. ] [ Designated as safety issue: No ]
    Relative difference in EELV expressed as difference in end-expiratory lung impedance during HFOV-only and HFOV-sigh

  • Regional ventilation distribution [ Time Frame: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day. ] [ Designated as safety issue: No ]
    Relative difference in regional EELV during HFOV-sigh vs HFOV-only expressed as change in regional end-expiratory lung impedance in predefined regions of interests (ROI), such as e.g. ventral, mid-ventral, mid-dorsal and dorsal lung areas.


Secondary Outcome Measures:
  • Global changes in oscillatory volume (Vosv): [ Time Frame: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day. ] [ Designated as safety issue: No ]
    Relative difference in oscillatory volume expressed as change in impedance amplitude during HFOV-only and HFOV-sigh, if measurable

  • Regional difference in oscillatory volume [ Time Frame: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day. ] [ Designated as safety issue: No ]
    Relative difference in regional oscillatory volume expressed as change in impedance amplitude during HFOV-only and HFOV-sigh in predefined regions of interests (ROI), such as e.g. ventral, mid-ventral, mid-dorsal and dorsal

  • Regional distribution of sigh-breaths volume [ Time Frame: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day. ] [ Designated as safety issue: No ]
    Regional distribution of sigh-breaths during HFOV-sigh based on impedance amplitude of sigh-breaths in predefined ROIs, such as e.g. ventral, mid-ventral, mid-dorsal and dorsal

  • Global inhomogeneity index [ Time Frame: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day. ] [ Designated as safety issue: No ]
    Calculated for oscillatory volume and tidal volume during sigh breaths respectively

  • Phase angle analyses [ Time Frame: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day. ] [ Designated as safety issue: No ]
    • Description of regional filling characteristic by phase angle analysis, measuring synchronicity of emptying and filling of different lung regions during sigh-breaths.
    • Aim to analyse if a possible increase in EELV during HFOV-sigh is distributed to different ROIs with different timing.

  • vital parameters during HFOV-sigh vs HFOV-only [ Time Frame: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day. ] [ Designated as safety issue: No ]
    relative changes in fraction of inspired oxygen (FiO2), oxygensaturation and heart rate


Estimated Enrollment: 16
Study Start Date: November 2013
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Other: 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

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: 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


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   24 Weeks to 44 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01962818

Contacts
Contact: Luke Jardine, neonatologist +61 3163 8250 luke.jardine@mater.org.au
Contact: Judith Hough, phd +61 3163 8250 judith.hough@mater.org.au

Locations
Australia, Queensland
Department of Neonatology, Mater Mothers Hospital Not yet recruiting
Brisbane, Queensland, Australia, 4101
Principal Investigator: Christian Heiring, neonatologist         
Principal Investigator: Luke Jardine, Neonatologist         
Sub-Investigator: Andreas Schibler, phd         
Sub-Investigator: Judith Hough, phd         
Sub-Investigator: Andrew Shearman, scientist         
Sub-Investigator: Deborah Caldararo, RN         
Sub-Investigator: Gorm Greisen, professor         
Sponsors and Collaborators
Rigshospitalet, Denmark
Investigators
Principal Investigator: Christian Heiring, neonatologist Department of Neonatology, Rigshospitalet, Copenhagen
Principal Investigator: Luke Jardine, neonatologist Department of Neonatology, Mater Mothers Hospital, Brisbane, Australia
  More Information

No publications provided

Responsible Party: Christian Heiring, Neonatologist, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01962818     History of Changes
Other Study ID Numbers: 1936M
Study First Received: October 9, 2013
Last Updated: October 10, 2013
Health Authority: Australia: National Health and Medical Research Councils, National Statement on Ethical Conduct in Human Research

Keywords provided by Rigshospitalet, Denmark:
Respiratory Distress Syndrome In Premature Infants
Bronchopulmonary Dysplasia
Ventilator-Induced Lung Injury
Functional Residual Capacity
Electric impedance tomography

Additional relevant MeSH terms:
Thoracic Injuries
Syndrome
Respiratory Distress Syndrome, Newborn
Bronchopulmonary Dysplasia
Lung Injury
Ventilator-Induced Lung Injury
Disease
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Wounds and Injuries

ClinicalTrials.gov processed this record on October 01, 2014