Does The Surfactant Administration by Aerosolization Effective?

NCT ID: NCT02825953

Last Updated: 2016-07-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

75 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-31

Study Completion Date

2017-01-31

Brief Summary

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The present study was designed to evaluate, in premature babies with RDS breathing spontaneously, the efficacy of combined treatment with nasal continuous positive airway pressure (CPAP) and aerosolized surfactant. The first objective of investigators is to assess the safety of surfactant nebulization in this clinical situation, and to find out whether treatment with aerosolized surfactant would reduce the need for mechanical ventilation. And other aim suggest that aerosolized dates compared with dates of INSURE (intubation-surfactant-extubation) and minimally invasive surfactant therapy (MIST) method.

Detailed Description

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Does The Surfactant Administration by Aerosolization of Respiratory Distress Syndrome effective in Spontaneously Breathing Premature Infants ? Endotracheal bolus application of natural surfactant has been shown to be an effective treatment for idiopathic respiratory distress syndrome (RDS), especially in premature neonates with weeks of pregnancy \> 27 week. However, patients are intubated nasotracheal or orotracheal for this form of treatment. This intubation carries potential risks of injuries to the dental lamina, the larynx, and the trachea, bronchopulmonary infections, and fluctuations in cerebral blood flow, intra- and periventricular haemorrhage (1). In addition, many babies with RDS who initially respond to surfactant therapy later develop chronic lung disease (CLD) (2). With this in mind, the investigators attempt to administer surfactant in a more gentle way, i.e. by nebulization. Administration by aerosol during spontaneous respiration is less traumatic and avoids intubation with the accompanying mechanical and infectious risks and pathophysiological effects.

The present study was designed to evaluate, in premature babies with RDS breathing spontaneously, the efficacy of combined treatment with nasal continuous positive airway pressure (CPAP) and aerosolized surfactant. The first objective of investigators is to assess the safety of surfactant nebulization in this clinical situation, and to find out whether treatment with aerosolized surfactant would reduce the need for mechanical ventilation. And other aim suggest that aerosolized dates compared with dates of INSURE (intubation-surfactant-extubation) and minimally invasive surfactant therapy (MIST) method.

Seventy-five newborn babies from neonatal intensive care unit (NICU) of Yuzuncu Yil University Medical Scholl (Van, Turkey) will be randomized to treatment with nebulized surfactant (Curosurf®, Chiesi Pharmaceutics, Parma, Italy) or to two control groups receiving INSURE and MIST method. The study will be conducted with 75 infants, 25 in each group. Randomization will be central and performed using sealed envelopes kept at the neonatal ward of Yuzuncu Yil University Medical Centre Hospital. Informed consent was obtained from all parents before randomization. Inclusion criteria are corrected gestational age \>26 week or \<34 week, age 2-36 h, clinically and radiologically diagnosed progressive RDS, FiO2 needed to maintain SaO2 85-95%; \>0.4, and no evident lung or cardiovascular malformation.

The surfactant aerosol will generate with a ultrasonic nebulizer (Aeroneb Pro; Aerogen, Inc., Sunnyvale, CA) and administer via the nasal continuous positive airway pressure (NCPAP) equipment into the Laryngeal Mask Airway (LMA). Surfactant will be diluted to 40 mg/ml with saline before nebulization. These modifications will be introduced to enhance the delivery of nebulized material to the lungs (3). In the control groups, the babies will be supported with the same type of NCPAP equipment, after given surfactant via endotracheal bolus application and MIST method. Parameters will be documented at three different times, namely before application of surfactant (200 mg/kg BW), and 2 h, 6 h after completion of nebulization or application of others.

The infants will be stabilised on NCPAP (Neopuff; Fisher and Paykel, Auckland, New Zealand) in the delivery room and during transport to the NICU. NCPAP or NIPPV will be started within 30 min of birth immediately after randomisation. Both NCPAP and NIPPV will be delivered by a neonatal ventilator (Engström Carestation; GE Healthcare, Madison, USA) via short, binasal Cannula (RAM Cannula; Neotech, Valencia, CA). NCPAP pressure will be set at 5-6 cm H2O, and NIPPV will be set in a non-synchronised mode at 20-30 bpm, with positive end-expiratory pressure of 5-6 cm H2O and peak inspiratory pressure of 15-20 cm H2O. FiO2 will be titrated at 0.21-0.50 to maintain an oxygen saturation level of 90%-95%, as measured via pulse oximeter. Under non-invasive ventilation, the surfactant will be administered as a rescue therapy if the infant required ≥0.40 FiO2 to maintain the target saturation level of 90%-95%.

Findings in chest radiograms before inclusion and head ultrasound images taken as soon as possible according to the clinical situation will be evaluated and graded according to criteria defined by Papile et al. (4) and Kero et al.(5) CLD will be defined as need for supplemental oxygen at 36 wk gestational age.

Statistical evaluation Data will be analyzed using the 20 Windows Version of Statistical Package for the Social Sciences (SPSS) Program (Chicago, IL, USA).

Data were compared using unpaired t-test and Chi-square test, and p-values below \<0.05 were considered statistically significant.

Ethical approval The study was approved by the regional ethics committee at the Yuzuncu Yil University Institute, Van, Turkey.

The regional ethics committee No: 05.05.2015/09

Conditions

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Respiratory Distress Syndrome Surfactant Administration by Aerosolization

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators

Study Groups

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Nebulized surfactant

For randomisatio, each infant will be randomly assigned to nasal continuous positive airway pressure (NCPAP) or non-invasive intermittent positive-pressure ventilation (NIPPV), and than premature babies with RDS breathing spontaneously will be administered surfactant by nebulizer.

Group Type ACTIVE_COMPARATOR

surfactant

Intervention Type DRUG

the investigators attempt to administer surfactant in a more gentle way, i.e. by nebulization, by minimally invasive surfactant therapy, and endotracheal bolus application of natural surfactant

nasal continuous positive airway pressure

Intervention Type DEVICE

each infant will be randomly assigned to nasal continuous positive airway pressure (NCPAP) or non-invasive intermittent positive-pressure ventilation (NIPPV). The infants will be stabilised on NCPAP (Neopuff; Fisher and Paykel, Auckland, New Zealand) in the delivery room and during transport to the NICU. NCPAP or NIPPV will be started within 30 min of birth immediately after randomisation. Both NCPAP and NIPPV will be delivered by a neonatal ventilator (Engström Carestation; GE Healthcare, Madison, USA) via short, binasal Cannula (RAM Cannula; Neotech, Valencia, CA).

non-invasive intermittent positive-pressure ventilation

Intervention Type DEVICE

each infant will be randomly assigned to nasal continuous positive airway pressure (NCPAP) or non-invasive intermittent positive-pressure ventilation (NIPPV). The infants will be stabilised on NCPAP (Neopuff; Fisher and Paykel, Auckland, New Zealand) in the delivery room and during transport to the NICU. NCPAP or NIPPV will be started within 30 min of birth immediately after randomisation. Both NCPAP and NIPPV will be delivered by a neonatal ventilator (Engström Carestation; GE Healthcare, Madison, USA) via short, binasal Cannula (RAM Cannula; Neotech, Valencia, CA).

Neopuff

Intervention Type DEVICE

Fisher and Paykel, Auckland, New Zealand

neonatal ventilator

Intervention Type DEVICE

GE Healthcare, Madison, USA

Endotracheal bolus application

For randomisatio, each infant will be randomly assigned to nasal continuous positive airway pressure (NCPAP) or non-invasive intermittent positive-pressure ventilation (NIPPV). The investigators will administer surfactant via fundamental method.

Group Type ACTIVE_COMPARATOR

surfactant

Intervention Type DRUG

the investigators attempt to administer surfactant in a more gentle way, i.e. by nebulization, by minimally invasive surfactant therapy, and endotracheal bolus application of natural surfactant

nasal continuous positive airway pressure

Intervention Type DEVICE

each infant will be randomly assigned to nasal continuous positive airway pressure (NCPAP) or non-invasive intermittent positive-pressure ventilation (NIPPV). The infants will be stabilised on NCPAP (Neopuff; Fisher and Paykel, Auckland, New Zealand) in the delivery room and during transport to the NICU. NCPAP or NIPPV will be started within 30 min of birth immediately after randomisation. Both NCPAP and NIPPV will be delivered by a neonatal ventilator (Engström Carestation; GE Healthcare, Madison, USA) via short, binasal Cannula (RAM Cannula; Neotech, Valencia, CA).

non-invasive intermittent positive-pressure ventilation

Intervention Type DEVICE

each infant will be randomly assigned to nasal continuous positive airway pressure (NCPAP) or non-invasive intermittent positive-pressure ventilation (NIPPV). The infants will be stabilised on NCPAP (Neopuff; Fisher and Paykel, Auckland, New Zealand) in the delivery room and during transport to the NICU. NCPAP or NIPPV will be started within 30 min of birth immediately after randomisation. Both NCPAP and NIPPV will be delivered by a neonatal ventilator (Engström Carestation; GE Healthcare, Madison, USA) via short, binasal Cannula (RAM Cannula; Neotech, Valencia, CA).

Neopuff

Intervention Type DEVICE

Fisher and Paykel, Auckland, New Zealand

neonatal ventilator

Intervention Type DEVICE

GE Healthcare, Madison, USA

Minimally invasive surfactant therapy

For randomisatio, each infant will be randomly assigned to nasal continuous positive airway pressure (NCPAP) or non-invasive intermittent positive-pressure ventilation (NIPPV). After randomisation, the investigators will administer surfactant via minimally invasive surfactant therapy (MIST) method which is recently very popular method

Group Type ACTIVE_COMPARATOR

surfactant

Intervention Type DRUG

the investigators attempt to administer surfactant in a more gentle way, i.e. by nebulization, by minimally invasive surfactant therapy, and endotracheal bolus application of natural surfactant

nasal continuous positive airway pressure

Intervention Type DEVICE

each infant will be randomly assigned to nasal continuous positive airway pressure (NCPAP) or non-invasive intermittent positive-pressure ventilation (NIPPV). The infants will be stabilised on NCPAP (Neopuff; Fisher and Paykel, Auckland, New Zealand) in the delivery room and during transport to the NICU. NCPAP or NIPPV will be started within 30 min of birth immediately after randomisation. Both NCPAP and NIPPV will be delivered by a neonatal ventilator (Engström Carestation; GE Healthcare, Madison, USA) via short, binasal Cannula (RAM Cannula; Neotech, Valencia, CA).

non-invasive intermittent positive-pressure ventilation

Intervention Type DEVICE

each infant will be randomly assigned to nasal continuous positive airway pressure (NCPAP) or non-invasive intermittent positive-pressure ventilation (NIPPV). The infants will be stabilised on NCPAP (Neopuff; Fisher and Paykel, Auckland, New Zealand) in the delivery room and during transport to the NICU. NCPAP or NIPPV will be started within 30 min of birth immediately after randomisation. Both NCPAP and NIPPV will be delivered by a neonatal ventilator (Engström Carestation; GE Healthcare, Madison, USA) via short, binasal Cannula (RAM Cannula; Neotech, Valencia, CA).

Neopuff

Intervention Type DEVICE

Fisher and Paykel, Auckland, New Zealand

neonatal ventilator

Intervention Type DEVICE

GE Healthcare, Madison, USA

Interventions

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surfactant

the investigators attempt to administer surfactant in a more gentle way, i.e. by nebulization, by minimally invasive surfactant therapy, and endotracheal bolus application of natural surfactant

Intervention Type DRUG

nasal continuous positive airway pressure

each infant will be randomly assigned to nasal continuous positive airway pressure (NCPAP) or non-invasive intermittent positive-pressure ventilation (NIPPV). The infants will be stabilised on NCPAP (Neopuff; Fisher and Paykel, Auckland, New Zealand) in the delivery room and during transport to the NICU. NCPAP or NIPPV will be started within 30 min of birth immediately after randomisation. Both NCPAP and NIPPV will be delivered by a neonatal ventilator (Engström Carestation; GE Healthcare, Madison, USA) via short, binasal Cannula (RAM Cannula; Neotech, Valencia, CA).

Intervention Type DEVICE

non-invasive intermittent positive-pressure ventilation

each infant will be randomly assigned to nasal continuous positive airway pressure (NCPAP) or non-invasive intermittent positive-pressure ventilation (NIPPV). The infants will be stabilised on NCPAP (Neopuff; Fisher and Paykel, Auckland, New Zealand) in the delivery room and during transport to the NICU. NCPAP or NIPPV will be started within 30 min of birth immediately after randomisation. Both NCPAP and NIPPV will be delivered by a neonatal ventilator (Engström Carestation; GE Healthcare, Madison, USA) via short, binasal Cannula (RAM Cannula; Neotech, Valencia, CA).

Intervention Type DEVICE

Neopuff

Fisher and Paykel, Auckland, New Zealand

Intervention Type DEVICE

neonatal ventilator

GE Healthcare, Madison, USA

Intervention Type DEVICE

Other Intervention Names

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Curosurf NCPAP NIPPV Engström Carestation

Eligibility Criteria

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Inclusion Criteria

* Corrected gestational age \>26 week or \<34 week,
* Age 2-36 h
* Clinically and radiologically diagnosed progressive RDS,
* FiO2 needed to maintain SaO2 85-95%; \>0.4
* No evident lung or cardiovascular malformation.

Exclusion Criteria

* Corrected gestational age \<26 week or \>34 week,
* Age \>36 h
* Premature babies with RDS but no breathing spontaneously
* Evident lung or cardiovascular malformation.
Minimum Eligible Age

26 Weeks

Maximum Eligible Age

34 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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nihat demir

OTHER

Sponsor Role lead

Responsible Party

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nihat demir

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

References

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Cowan F, Whitelaw A, Wertheim D, Silverman M. Cerebral blood flow velocity changes after rapid administration of surfactant. Arch Dis Child. 1991 Oct;66(10 Spec No):1105-9. doi: 10.1136/adc.66.10_spec_no.1105.

Reference Type RESULT
PMID: 1750756 (View on PubMed)

Mercier CE, Soll RF. Clinical trials of natural surfactant extract in respiratory distress syndrome. Clin Perinatol. 1993 Dec;20(4):711-35.

Reference Type RESULT
PMID: 8131364 (View on PubMed)

Berggren E, Liljedahl M, Winbladh B, Andreasson B, Curstedt T, Robertson B, Schollin J. Pilot study of nebulized surfactant therapy for neonatal respiratory distress syndrome. Acta Paediatr. 2000 Apr;89(4):460-4. doi: 10.1080/080352500750028195.

Reference Type RESULT
PMID: 10830460 (View on PubMed)

Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. 1978 Apr;92(4):529-34. doi: 10.1016/s0022-3476(78)80282-0.

Reference Type RESULT
PMID: 305471 (View on PubMed)

Kero PO, Makinen EO. Comparison between clinical and radiological classification of infants with the respiratory distress syndrome (RDS). Eur J Pediatr. 1979 Apr 3;130(4):271-8. doi: 10.1007/BF00441363.

Reference Type RESULT
PMID: 436851 (View on PubMed)

Other Identifiers

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YYU-09

Identifier Type: -

Identifier Source: org_study_id

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