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

Related Clinical Trial
The Budesonide in Babies (BiB) Trial Follow-up Results of Newborns With Tracheostomy Safety of Sildenafil in Premature Infants With Severe Bronchopulmonary Dysplasia Prolonged Outcomes After Nitric Oxide (PrONOx) A Study of Tobacco Smoke and Children With Respiratory Illnesses Delivery Room CPAP in Extremely Low Birth Weight Infants Dexamethasone Therapy in VLBW Infants at Risk of CLD Palivizumab for Prevention of Severe Respiratory Syncytial Virus Infection in Russian Children Estimating Length of Endotracheal Tube Insertion Using Gestational Age or Nasal-Tragus Length in Newborn Infants MRI as a Means to Measure Lung Function: Non-Invasive Imaging in Neonates and Children Seattle-PAP Bubble Nasal CPAP and Work of Breathing High Frequency Oscillatory Ventilation Combined With Intermittent Sigh Breaths: Effects on Blood Oxygenation and Stability of Oxygenation Comparing Two Different Modes of Ventilation in Pretem Neonates Bilevel VG and PRVC High Frequency Ventilation in Premature Infants (HIFI) Early Caffeine in Preterm Neonates High Frequency Oscillatory Ventilation Combined With Intermittent Sigh Breaths: Effects on Lung Volume Monitored by Electric Tomography Impedance. Functional and Lymphocytic Markers of Respiratory Morbidity in Hyperoxic Preemies Vitamin A Supplementation for Extremely-Low-Birth-Weight Infants Non-invasive Respiratory Support in Preterm Infants Pilot Trial of Surfactant Booster Prophylaxis For Ventilated Preterm Neonates Randomized Trial of Nasal Continuous Positive Airway Pressure or Synchronized Nasal Ventilation in Premature Infants. The Effect of Surfactant Dose on Outcomes in Preterm Infants With RDS Work of Breathing During Non-invasive Ventilation in Premature Neonates Inhaled Nitric Oxide for Preventing Chronic Lung Disease in Premature Infants Intratracheal Budesonide/Surfactant Prevents BPD Bronchopulmonary Disease (BPD) Patient Registry Premature Birth and Its Sequelae in Women Inhaled NO in Prevention of Chronic Lung Disease The Effects of Position on the Oxygenation Instability of Premature Infants as Documented by SpO2 Histograms Trial of Late Surfactant to Prevent BPD: A Pilot Study in Ventilated Preterm Neonates Receiving Inhaled Nitric Oxide Continuous Positive Airway Pressure Via Binasal Prong vs Nasal Mask: a Randomised Controlled Trial Randomized Trial of Hydrocortisone in Very Preterm High-Risk Infants Early NCPAP Before Surfactant Treatment in Very Preterm Infants With RDS Exosurf Neonatal and Survanta for Treatment of Respiratory Distress Syndrome Continuous Versus Intermittent Bolus Feeding in Very Preterm Infants – Effect on Respiratory Morbidity Feasibility and Impact of Volume Targeted Ventilation in the Delivery Room Growth of Airways and Lung Tissues in Premature and Healthy Infants Duration of Continuous Positive Airway Pressure and Pulmonary Function Testing in Preterm Infants Assessment of Lung Structure and Function of Infants Born Prematurely Post-hospitalization Nursing Effectiveness (PHONE) Study Assessment of the Pulmonary Diffusion Capacity in Healthy Infants and Infants With Chronic Lung Disease NCPAP + Heliox as a Treatment for Infant Respiratory Distress Syndrome (RDS) Neurotrophin Expression in Infants as a Predictor of Respiratory and Neurodevelopmental Outcomes Inhaled Beclomethasone to Prevent Chronic Lung Disease Work of Breathing in Premature Infants at Discharge Efficacy of Recombinant Human Clara Cell 10 Protein (rhCC10) Administered to Premature Neonates With Respiratory Distress Syndrome Hydrocortisone for BPD Clinic Features and Outcome of BPD (SGBPD) Neolifes Heart – Pulmonary Hypertension in Preterm Children Thrombocytopoiesis and Platelet Homeostasis in Infants With Bronchoplumonary Dysplasia Management of Hyponatremia in Preterm Infants on Diuretics Steroids and Surfactant in Extremely Low Gestation Age Infants Dose Escalation Trial Respiratory Outcome at Adolescence of Very Low Birthweight Infants Surfactant Administration During Spontaneous Breathing Determining the Effect of Spironolactone on Electrolyte Supplementation in Preterm Infants With Chronic Lung Disease Developmental Sequelae of Severe Chronic Lung Disorders Long-term Safety and Efficacy Follow-up Study of PNEUMOSTEM® in Patients Who Completed PNEUMOSTEM® Phase-I Study Indoor Air Quality and Respiratory Morbidity in School-Aged Children With BPD Study of Nasal Ventilation In Preterm Infants To Decrease Time on The Respirator Improving Prematurity-Related Respiratory Outcomes at Vanderbilt Study of Inhaled Nitric Oxide (iNO) and Respiratory Outcomes in Late Preterm Infants Follow-up Study of Safety and Efficacy in Subjects Who Completed PNEUMOSTEM® Phase II (MP-CR-012) Clinical Trial Follow-up Safety and Efficacy Evaluation on Subjects Who Completed PNEUMOSTEM® Phase-II Clinical Trial Tidal Neonatal NO, Vitamins A and D, and Infant Lung Disease – The AD-ON Study Nasal Mask and Prong Use in Non-invasive Ventilation for Newborns Azithromycin in the Prevention of Lung Injury in Premature Newborn Randomized Control Trial: Synchronized Non-invasive Positive Pressure Ventilation Versus Non Synchronized Non Invasive Positive Pressure Ventilation in Extremely Low Birth Weight Infants Neurally Adjusted Ventilatory Assist vs Proportional Assist Ventilation MRI in BPD Subjects A Safety Study of IV Stem Cell-derived Extracellular Vesicles (UNEX-42) in Preterm Neonates at High Risk for BPD Hypercapnia and Its Association With Long-term Respiratory Morbidities in Premature Infants With Chronic Lung Disease Early Versus Late Caffeine for ELBW Newborns Assessment of Lung Aeration at Birth MRI of Lung Structure and Function in Preterm Children BPD Saturation TARgeting Use of Human Milk Cream to Decrease Length of Stay in Extremely Premature Infants Effect of Synchronized vs. Continuous HFNC Using NAVA on WOB in Infants With BPD Antecedents of Bronchopulmonary Dysplasia Pulmonary Outcomes of Bronchopulmonary Dysplasia in Young Adulthood Aerosolized Albuterol Use in Severe BPD Late Sequelae of Bronchopulmonary Dysplasia Montelukast in Very Low Birthweight Infants Preterm Infant Inhaled Albuterol Dosing 129Xe MRI in Pediatric Population With BPD Investigation of Polymorphisms in Bronchopulmonary Dysplasia In Turkish Population Pulmonary MRI of Ex-preterm Children With and Without BPD To Understand Risk of Emphysematous Changes Comparison of Classification Standards of BPD in Premature Infants Inhaled Corticosteroids for Treatment of Bronchopulmonary Dysplasia Safety of Sildenafil in Premature Infants Phase II Pilot Study of Early Cortisol Replacement to Prevent Bronchopulmonary Dysplasia Intratracheal Umbilical Cord-derived Mesenchymal Stem Cells for Severe Bronchopulmonary Dysplasia Phase III Randomized, Double-Blind Study of Dexamethasone Vs Dexamethasone/Methylprednisolone Vs Placebo for Bronchopulmonary Dysplasia Impact of an Exercise Program for Children Aged 4 to 6 Years With Bronchopulmonary Dysplasia Trial II of Lung Protection With Azithromycin in the Preterm Infant Forced Oscillometry in Infants With Bronchopulmonary Dysplasia The Efficacy and Safety of Montelukast Sodium in the Prevention of Bronchopulmonary Dysplasia L-citrulline and Pulmonary Hypertension Associated With Bronchopulmonary Dysplasia The Role of Anti-Reflux Surgery for Gastroesophageal Reflux Disease in Premature Infants With Bronchopulmonary Dysplasia Enteral Zinc to Improve Growth in Infants at Risk for Bronchopulmonary Dysplasia Fluid Filled Lung Oxygenation Assistance Trial Trial of Late Surfactant for Prevention of Bronchopulmonary Dysplasia Predictors of Pulmonary Hypertension Risk in Premature Infants With Bronchopulmonary Dysplasia Exogenous Surfactant in Very Preterm Neonates in Prevention of Bronchopulmonary Dysplasia Follow-Up Study of Safety and Efficacy of Pneumostem® in Premature Infants With Bronchopulmonary Dysplasia Risk Factors in Bronchopulmonary Dysplasia (Newborn Lung Project) Pilot Study of Topical Steroid for Prevention of Chronic Lung Disease in Extremely Premature Infants. Bronchopulmonary Dysplasia: From Neonatal Chronic Lung Disease to Early Onset Adult COPD Gastrin-Releasing Peptide and Bronchopulmonary Dysplasia Benchmarking Initiative to Reduce Bronchopulmonary Dysplasia Physiologic Definition of Bronchopulmonary Dysplasia Safety and Efficacy of PNEUMOSTEM® in Premature Infants at High Risk for Bronchopulmonary Dysplasia (BPD) – a US Study Inhaled Nitric Oxide for Pulmonary Hypertension and Bronchopulmonary Dysplasia Human Mesenchymal Stem Cells For Infants At High Risk For Bronchopulmonary Dysplasia SURFAXIN® Treatment for Prevention of Bronchopulmonary Dysplasia (BPD) in Very Low Birth Weight (VLBW) Infants. Safety of Furosemide in Premature Infants at Risk of Bronchopulmonary Dysplasia (BPD) Mesenchymal Stem Cells for The Treatment of Bronchopulmonary Dysplasia in Infants p16Ink4a in Bronchopulmonary Dysplasia in Children Transpyloric Feeding in Severe Bronchopulmonary Dysplasia Follow-Up Study of Mesenchymal Stem Cells for Bronchopulmonary Dysplasia Phase 1 Intravenous Citrulline for the Prevention of Bronchopulmonary Dysplasia in Preterm Infants Epidemiological Study for Bronchopulmonary Dysplasia (BPD) in China PREMILOC Trial to Prevent Bronchopulmonary Dysplasia in Very Preterm Neonates Stem Cells for Bronchopulmonary Dysplasia Hydrotherapy in Premature Infants With Bronchopulmonary Dysplasia Inhaled Nitric Oxide (INO) for the Prevention of Bronchopulmonary Dysplasia (BPD) in Preterm Infants Prospective Study on Plasma Pro-endothelin-1 in Predicting Bronchopulmonary Dysplasia Interest of Pulmonary Ultrasound to Predict Evolution Towards Bronchopulmonary Dysplasia in Premature Infants at Gestational Age Less Than or Equal to 34 Weeks of Gestation Safety and Efficacy Evaluation of PNEUMOSTEM® Treatment in Premature Infants With Bronchopulmonary Dysplasia Inhaled Extra-fine Hydrofluoalkane-beclomethasone (QVAR) in Premature Infants With Bronchopulmonary Dysplasia (BPD) Efficacy and Safety of Inhaled Budesonide in Very Preterm Infants at Risk for Bronchopulmonary Dysplasia Study to Justify Steroid Use in Preterm Neonates to Prevent Bronchopulmonary Dysplasia Efficacy of Adding Budesonide to Poractant Alfa to Prevent Bronchopulmonary Dysplasia. Human Mesenchymal Stem Cells For Bronchopulmonary Dysplasia Human Mesenchymal Stem Cells For Moderate and Severe Bronchopulmonary Dysplasia Genetic Susceptibility for Bronchopulmonary Dysplasia in Preterm Infants Respiratory Management of Preterm Infants and Bronchopulmonary Dysplasia

Brief Title

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

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

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.
    

Detailed Description

      Ventilator induced lung injury (VILI) is an important etiological factor in the pathogenesis
      of bronchopulmonary dysplasia (BPD), defined as need for respiratory support or supplemental
      oxygen at 36 weeks post-conceptual age. Despite advances in antenatal and neonatal care,
      50-80% of very-low-birth-weight infants will be ventilated during their neonatal admission.
      Accordingly, further development of neonatal ventilation strategies with specific emphasis on
      lung-protective ventilation remains an important research field. Volutrauma and
      atelectotrauma caused by excessive tidal volume and insufficient lung recruitment
      respectively rather than barotrauma are today considered as the most important factors for
      VILI. High frequency oscillatory ventilation (HFOV) provides effective gas exchange with
      minimal pressure fluctuation around a continuous distending pressure and therefore small
      tidal volume and is in theory more lung protective. However results from randomized
      controlled trials comparing HFOV with conventional ventilation have been conflicting and
      meta-analyses have not shown clear evidence that HFOV is safer or more effective than
      conventional ventilation neither when used as initial strategy nor as rescue strategy in
      preterm babies. Accordingly HFOV still has no absolute indication and is mostly used as a
      rescue treatment. Early animal studies showed that recruitment and maintenance of functional
      residual capacity (FRC) during HFOV ("open lung concept") could reduce lung injury. Because
      of fear of barotrauma, lung recruitment was initially achieved by superimposing conventional
      ventilation (CV) breaths on top of HFOV with much lower mean airway pressure (MAP) than what
      is used today. Today most neonatologists provide "open lung HFOV" by delivering a higher MAP
      using oxygenation as an indirect guide of lung recruitment. In some units a clinical praxis
      has evolved combining HFOV (using "modern" high MAP) with recurrent sigh-breaths (HFOV-sigh)
      delivered as modified conventional inflations at a rate of 3/min. The clinical observation
      is, that when compared to standard HFOV, HFOV-sigh leads to more stable oxygenation, quicker
      weaning in FiO2 and MAP, and shorter ventilation. This approach seems to be encouraged by a
      number of neonatologist.

      Electric Impedance Tomography (EIT) enables measurement and mapping of regional ventilation
      distribution, end-expiratory lung volume (EELV) and other respiratory physiological
      parameters. EIT generates cross-sectional images of the studied subject based on the
      measurement of surface electrical potentials resulting from an excitation with known small
      electrical currents (5 mAmp and 50 kHz). Both the voltage measurements and current injections
      take place between pairs of conventional self-adhesive surface electrodes of a 16-electrode
      array attached on the chest circumference. Electrical impedance tomography scans are
      generated from the collected potential differences and the known excitation currents using
      weighted back-projection in a 32x32 pixel matrix. Each pixel of the scan shows the
      instantaneous local impedance. EIT has been shown to be a valid and safe tool in neonates to
      monitor changes in global and regional lung ventilation and EELV.

      Combining HFOV with conventional breaths has only been reported in a limited number of
      studies and only with focus on HFOV combined with conventional breaths at normal rate showing
      a possible benefit. Similar results have been reported when comparing High frequency Jet
      Ventilation (HFVJ) combined with conventional breaths at normal rate with HFVJ alone. To our
      knowledge only one human trial comparing standard HFOV with HFOV combined with recruitment
      breaths at low rate has been registered but never published (Texas Infant Star Trial).

      The clinical observation is that oxygenation during HFOV-sigh seems to be improved which is
      considered to be an indirect sign of improved lung volume. However no clinical studies
      estimating lung volume during HFOV-sigh exist to confirm or dispute this, which is the main
      reason we propose this study.

      Ideally, during HFOV the MAP should be set at a level at which lung volume is optimal.
      However in some situations the cardiovascular status of the patient does not allow the MAP to
      be increased to this level, in which case combining HFOV with sigh-breaths at a lower MAP
      could be an alternative way of optimizing lung volume.

      The purpose of this study is to investigate the effect of HFOV-sigh compared with HFOV-only
      on EIT derived measurements of EELV and regional ventilation distribution and other
      respiratory physiological parameters such as heart rate and respiratory rate.

      Research question:

      In ventilated newborn infants, does combining high frequency oscillatory ventilation (HFOV)
      with intermittent sigh breaths result in increased end-expiratory lung volume (EELV) and more
      homogenous distribution of ventilation when compared to standard HFOV without sigh-breaths.
      Lung volume and distribution of ventilation will be monitored by electric impedance
      tomography (EIT).

      Hypothesis and Aims of project:

      Primary hypothesis of the study is that end-expiratory lung volume (EELV) during HFOV
      combined with sigh-breaths (HFOV-sigh) is relatively higher than EELV during HFOV without
      HFOV (HFOV-only), and that regional distribution of ventilation will be more homogenous
      indicating a more homogenous lung-recruitment. The following specific aims of this study will
      address these hypotheses:

        -  To determine if there is a significant difference in global and regional EELV measured
           by EIT between HFOV-sigh and HFOV-only

        -  To determine if there is a significant difference in spatial distribution of ventilation
           and timing of ventilation between HFOV-sigh and HFOV-only using specific EIT derived
           calculation

        -  To determine if there is a significant difference in other respiratory variables, such
           as heart rate (HR), oxygen saturation (SpO2) and spontaneous breathing rate between
           HFOV-sigh and HFOV-only

        -  To provide information on feasibility and data on treatment effect of HFOV-sigh to
           assist in planning a larger study.
    


Study Type

Interventional


Primary Outcome

Global changes in end expiratory lung volume (EELV)

Secondary Outcome

 Global changes in oscillatory volume (Vosv):

Condition

Respiratory Distress Syndrome In Premature Infants

Intervention

HFOV combined with sigh breaths

Study Arms / Comparison Groups

 HFOV-sigh at start
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Other

Estimated Enrollment

16

Start Date

January 2014

Completion Date

July 2019

Primary Completion Date

July 2018

Eligibility 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).
      

Gender

All

Ages

24 Weeks - 44 Weeks

Accepts Healthy Volunteers

No

Contacts

Christian Heiring, neonatologist, , 

Location Countries

Australia

Location Countries

Australia

Administrative Informations


NCT ID

NCT01962818

Organization ID

1936M


Responsible Party

Principal Investigator

Study Sponsor

Rigshospitalet, Denmark


Study Sponsor

Christian Heiring, neonatologist, Principal Investigator, Department of Neonatology, Rigshospitalet, Copenhagen


Verification Date

August 2018