RDS of PrematurityPhase 2/3NIVNCT02259400
NIV Strategies for RDS in Preterm Infants. NIV (Non Invasive Ventilation), RDS (Respiratory Distress Syndrome)
A Phase 2/3 study testing NSIPPV and BiPAP in people with RDS of Prematurity, run by Azienda Ospedaliera Universitaria Policlinico "G. Martino".
Trial summary
The purpose of this study is to determine whether two different strategies of Non Invasive Ventilation (NIV) have different effect on length and failure of NIV support in preterm infants with respiratory distress syndrome (RDS). Read more about this study
- Who is it for?
- Ages Up to 2 hours
- Conditions the study is for
- RDS of Prematurity
- What is being tested?
- NSIPPV and BiPAP
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 280 participants
- Where
- No sites listed yet
- Study dates
- Jan 2010to Dec 2012
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 2 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- All inborn VLBW infants (birthweight less than 1500 g and Gestational Age < 32 wks) with signs of RDS, spontaneously breathing and only supported by N-CPAP, will be randomized within the first 2 hours of life to receive two different Non Invasive Ventilation (NIV) strategies.
Who cannot join
- Apneic or severely depressed newborns requiring invasive ventilation, within two hours from birth
- Newborns with genetic disease and/or with major congenital malformations
- Newborns for whom it was not obtained informed consent within two hours from birth
About this study
Official title: Noninvasive Ventilation Strategies for Early Treatment of RDS in Preterm Infants: An RCT
The purpose of this study is to determine whether two different strategies of Non Invasive Ventilation (NIV) have different effect on length and failure of NIV support in preterm infants with respiratory distress syndrome (RDS).
Read the detailed description
A Randomized Control Trial (RCT) conducted in two tertiary level Neonatal Intensive Care Unit (NICU). Ethical approval is needed. Informed and written consent will be obtained prior the delivery from the parents of the babies before the inclusion in the study. All inborn Very Low Birth Weight (VLBW) infants (Birthweight less than 1500 g and Gestational Age < 32 weeks) with signs of RDS, spontaneously breathing and only supported by nasal-Continuous Positive Airway Pressure (NCPAP) in NICU, will be randomized within the first 2 hours of life to receive two different Non Invasive Ventilation (NIV) strategies: Nasal Synchronized Intermittent Positive Pressure Ventilation (N-SIPPV) or Bilevel Continuous Positive Airway Pressure (BiPAP).
- Conditions
- RDS of Prematurity
- Being tested
- NSIPPV, BiPAP
- Keywords
- NIV, NSIPPV, BiPAP
- Medical subject headings
- Respiratory Distress Syndrome In Premature Infants
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NSIPPVDevice
In N-SIPPV, the physician will set : an initial PEEP of 4-6 cmH20; a peak inspiratory pressure (PIP) of 15-20 cmH2O ; an inspiratory time (IT) of 0.3-0.4 seconds; a flow rate of 6-10 L/min and a respiratory rate (RR) of 40 bpm with the lowest FiO2 to maintain a oxygen saturation (SpO2) of 88-93%. Weaning from N-SIPPV will be performed with a reduction of the RR to 15 bpm with a PIP of 10-15 cmH2O and PEEP of 4 cmH2O and will be stopped when the baby will not show signs of RDS and with a fraction of inspired oxygen (FiO2)< 0.3.
BiPAPDevice
In BiPAP, the physician will set : an initial low CPAP-level of 4-6 cmH20 and high CPAP-level of 8-9 cmH20; a time high of 1 second and a pressure exchange rate of 20 bpm, with the lowest FiO2 to maintain a SpO2 of 88-93%. Weaning will start with a progressive reduction of the set pressure exchange rate ( minimum 15 pressures exchange/min), followed by the reduction of the higher level-CPAP down to 6 cmH20 and lower level-CPAP down to 4 cmH20. BiPAP will be stopped when the baby will not show signs of RDS and with a FiO2 < 0.3.
| Study group | Role | What they receive |
|---|---|---|
| NSIPPV group | Active comparator | The NSIPPV is a conventional modality of mechanical ventilation delivered by the nasal ventilator device Giulia (Ginevri, Rome, Italy), that in noninvasive modality detects the inspiratory effort by means of a pneumotachograph, equipped with a fixed orifice (2 mm in diameter for LBW infants), positioned proximally to the nasal interface. Short bi-nasal prongs (NIV set, Ginevri, Rome, Italy), with different size according to infants'weight, will be used as interface. Receives: Device: NSIPPV |
| BiPAP group | Active comparator | The BiPAP is a modality of noninvasive respiratory support that provides two alternate different levels of CPAP in which the babies can breath spontaneously. The BiPAP will be delivered by the Infant Flow-driver device (Infant Flow System, Vyasis Corp,Yorba Linda, California (CA),USA) and bi-nasal prongs as interface (Vyasis Corp,Yorba Linda, CA,USA) with different size according to infants' weight. Receives: Device: BiPAP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of NIV Support
DURATION OF NON INVASIVE VENTILATION SUPPORT FOR RDS TREATMENT
Measured: 10 days
Failure of NIV Support
NUMBER OF NEWBORNS WHO FAILED WITH NON INVASIVE VENTILATION SUPPORT AND NEEDED INTUBATION AND INVASIVE MECHANICAL VENTILATION.
Measured: 10 days
Secondary outcomes (12)
Death
Measured: 2 month
Bronchopulmonary Dysplasia (BPD)
Measured: 36 weeks of postconceptional age or time of discharge
Pneumothorax (PNX)
Measured: 10 days
Intraventricular Hemorrhage (IVH)
Measured: 1 month of life
Periventricular Leukomalacia (PVL)
Measured: 3 month of life
Retinopathy of Prematurity (ROP)
Measured: 3 month of life
Patent Ductus Arteriosus Requiring Pharmacological Treatment (PDA)
Measured: first week of life
Necrotizing Enterocolitis (NEC)
Measured: 1 month
Newborns Who Received Multiple Surfactant Doses
Measured: 10 days
Early Onset Sepsis
Measured: 5days from birth
Late Onset Sepsis
Measured: after fifth days of life up 2 month of life
Death
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2014 (estimated)
- Study startJan 2010
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for RDS of PrematurityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 280 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliera Universitaria Policlinico "G. Martino"
- Sponsor type
- University, hospital or other
- Collaborators
- Vittore Buzzi Children's Hospital, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
- Responsible party
- Principal investigator, Vincenzo Salvo, MD, Azienda Ospedaliera Universitaria Policlinico
- Investigators
- Vincenzo V Salvo, MD, Principal investigator, Azienda Ospedaliera Universitaria Policlinico "G Martino" Messina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02259400
- Sponsor's protocol ID
- NIV/RDS-01
- Acronym
- NIV
- Status last verified
- Jan 2015
- First submitted
- 2 Oct 2014
- Last updated
- 18 Feb 2015
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Committee on Fetus and Newborn; American Academy of Pediatrics. Respiratory support in preterm infants at birth. Pediatrics. 2014 Jan;133(1):171-4. doi: 10.1542/peds.2013-3442. Epub 2013 Dec 30.
PubMed 24379228Stevens TP, Harrington EW, Blennow M, Soll RF. Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome. Cochrane Database Syst Rev. 2007 Oct 17;2007(4):CD003063. doi: 10.1002/14651858.CD003063.pub3.
PubMed 17943779Bhandari V. Nasal intermittent positive pressure ventilation in the newborn: review of literature and evidence-based guidelines. J Perinatol. 2010 Aug;30(8):505-12. doi: 10.1038/jp.2009.165. Epub 2009 Oct 22.
PubMed 19847188Kirpalani H, Millar D, Lemyre B, Yoder BA, Chiu A, Roberts RS; NIPPV Study Group. A trial comparing noninvasive ventilation strategies in preterm infants. N Engl J Med. 2013 Aug 15;369(7):611-20. doi: 10.1056/NEJMoa1214533.
PubMed 23944299Meneses J, Bhandari V, Alves JG, Herrmann D. Noninvasive ventilation for respiratory distress syndrome: a randomized controlled trial. Pediatrics. 2011 Feb;127(2):300-7. doi: 10.1542/peds.2010-0922. Epub 2011 Jan 24.
PubMed 21262883Roberts CT, Davis PG, Owen LS. Neonatal non-invasive respiratory support: synchronised NIPPV, non-synchronised NIPPV or bi-level CPAP: what is the evidence in 2013? Neonatology. 2013;104(3):203-9. doi: 10.1159/000353448. Epub 2013 Aug 28.
PubMed 23989138Ricotti A, Salvo V, Zimmermann LJ, Gavilanes AW, Barberi I, Lista G, Colivicchi M, Temporini F, Gazzolo D. N-SIPPV versus bi-level N-CPAP for early treatment of respiratory distress syndrome in preterm infants. J Matern Fetal Neonatal Med. 2013 Sep;26(13):1346-51. doi: 10.3109/14767058.2013.784255. Epub 2013 Apr 17.
PubMed 23488612Salvo V, Lista G, Lupo E, Ricotti A, Zimmermann LJ, Gavilanes AW, Barberi I, Colivicchi M, Temporini F, Gazzolo D. Noninvasive ventilation strategies for early treatment of RDS in preterm infants: an RCT. Pediatrics. 2015 Mar;135(3):444-51. doi: 10.1542/peds.2014-0895. Epub 2015 Feb 9.
PubMed 25667244
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Noninvasive Ventilation Strategies for Early Treatment of RDS in Preterm Infants: An RCT
- ClinicalTrials.gov ID
- NCT02259400
- Acronym / sponsor ID
- NIV / NIV/RDS-01
- Conditions
- RDS of Prematurity
- Keywords
- NIV, NSIPPV, BiPAP
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 280 participants (actual)
- Lead sponsor
- Azienda Ospedaliera Universitaria Policlinico "G. Martino"University, hospital or other
- Collaborators
- Vittore Buzzi Children's Hospital, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
- Study start
- Jan 2010
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 8 Oct 2014 (estimated)
- Results
- Posted 28 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether two different strategies of Non Invasive Ventilation (NIV) have different effect on length and failure of NIV support in preterm infants with respiratory distress syndrome (RDS).
Detailed description
A Randomized Control Trial (RCT) conducted in two tertiary level Neonatal Intensive Care Unit (NICU). Ethical approval is needed. Informed and written consent will be obtained prior the delivery from the parents of the babies before the inclusion in the study. All inborn Very Low Birth Weight (VLBW) infants (Birthweight less than 1500 g and Gestational Age < 32 weeks) with signs of RDS, spontaneously breathing and only supported by nasal-Continuous Positive Airway Pressure (NCPAP) in NICU, will be randomized within the first 2 hours of life to receive two different Non Invasive Ventilation (NIV) strategies: Nasal Synchronized Intermittent Positive Pressure Ventilation (N-SIPPV) or Bilevel Continuous Positive Airway Pressure (BiPAP).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NSIPPV group | Active comparator | Device: NSIPPVThe NSIPPV is a conventional modality of mechanical ventilation delivered by the nasal ventilator device Giulia (Ginevri, Rome, Italy), that in noninvasive modality detects the inspiratory effort by means of a pneumotachograph, equipped with a fixed orifice (2 mm in diameter for LBW infants), positioned proximally to the nasal interface. Short bi-nasal prongs (NIV set, Ginevri, Rome, Italy), with different size according to infants'weight, will be used as interface. |
| BiPAP group | Active comparator | Device: BiPAPThe BiPAP is a modality of noninvasive respiratory support that provides two alternate different levels of CPAP in which the babies can breath spontaneously. The BiPAP will be delivered by the Infant Flow-driver device (Infant Flow System, Vyasis Corp,Yorba Linda, California (CA),USA) and bi-nasal prongs as interface (Vyasis Corp,Yorba Linda, CA,USA) with different size according to infants' weight. |
Who may qualify
- Ages
- Up to 2 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- All inborn VLBW infants (birthweight less than 1500 g and Gestational Age < 32 wks) with signs of RDS, spontaneously breathing and only supported by N-CPAP, will be randomized within the first 2 hours of life to receive two different Non Invasive Ventilation (NIV) strategies.
Key exclusion criteria (3 listed)
- Apneic or severely depressed newborns requiring invasive ventilation, within two hours from birth
- Newborns with genetic disease and/or with major congenital malformations
- Newborns for whom it was not obtained informed consent within two hours from birth
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NSIPPVIn N-SIPPV, the physician will set : an initial PEEP of 4-6 cmH20; a peak inspiratory pressure (PIP) of 15-20 cmH2O ; an inspiratory time (IT) of 0.3-0.4 seconds; a flow rate of 6-10 L/min and a respiratory rate (RR) of 40 bpm with the lowest FiO2 to maintain a oxygen saturation (SpO2) of 88-93%. Weaning from N-SIPPV will be performed with a reduction of the RR to 15 bpm with a PIP of 10-15 cmH2O and PEEP of 4 cmH2O and will be stopped when the baby will not show signs of RDS and with a fraction of inspired oxygen (FiO2)< 0.3. | Device | NSIPPV group |
| BiPAPIn BiPAP, the physician will set : an initial low CPAP-level of 4-6 cmH20 and high CPAP-level of 8-9 cmH20; a time high of 1 second and a pressure exchange rate of 20 bpm, with the lowest FiO2 to maintain a SpO2 of 88-93%. Weaning will start with a progressive reduction of the set pressure exchange rate ( minimum 15 pressures exchange/min), followed by the reduction of the higher level-CPAP down to 6 cmH20 and lower level-CPAP down to 4 cmH20. BiPAP will be stopped when the baby will not show signs of RDS and with a FiO2 < 0.3. | Device | BiPAP group |
Primary outcome
Duration of NIV Support
Time frame: 10 days
DURATION OF NON INVASIVE VENTILATION SUPPORT FOR RDS TREATMENT
Failure of NIV Support
Time frame: 10 days
NUMBER OF NEWBORNS WHO FAILED WITH NON INVASIVE VENTILATION SUPPORT AND NEEDED INTUBATION AND INVASIVE MECHANICAL VENTILATION.
12 secondary outcomes
Death
Time frame: 2 month
Bronchopulmonary Dysplasia (BPD)
Time frame: 36 weeks of postconceptional age or time of discharge
Pneumothorax (PNX)
Time frame: 10 days
Intraventricular Hemorrhage (IVH)
Time frame: 1 month of life
Periventricular Leukomalacia (PVL)
Time frame: 3 month of life
Retinopathy of Prematurity (ROP)
Time frame: 3 month of life
Patent Ductus Arteriosus Requiring Pharmacological Treatment (PDA)
Time frame: first week of life
Necrotizing Enterocolitis (NEC)
Time frame: 1 month
Newborns Who Received Multiple Surfactant Doses
Time frame: 10 days
Early Onset Sepsis
Time frame: 5days from birth
Late Onset Sepsis
Time frame: after fifth days of life up 2 month of life
Death
Time frame: 1 month
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24379228Committee on Fetus and Newborn; American Academy of Pediatrics. Respiratory support in preterm infants at birth. Pediatrics. 2014 Jan;133(1):171-4. doi: 10.1542/peds.2013-3442. Epub 2013 Dec 30.
- Background: PubMed 17943779Stevens TP, Harrington EW, Blennow M, Soll RF. Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome. Cochrane Database Syst Rev. 2007 Oct 17;2007(4):CD003063. doi: 10.1002/14651858.CD003063.pub3.
- Background: PubMed 19847188Bhandari V. Nasal intermittent positive pressure ventilation in the newborn: review of literature and evidence-based guidelines. J Perinatol. 2010 Aug;30(8):505-12. doi: 10.1038/jp.2009.165. Epub 2009 Oct 22.
- Background: PubMed 23944299Kirpalani H, Millar D, Lemyre B, Yoder BA, Chiu A, Roberts RS; NIPPV Study Group. A trial comparing noninvasive ventilation strategies in preterm infants. N Engl J Med. 2013 Aug 15;369(7):611-20. doi: 10.1056/NEJMoa1214533.
- Background: PubMed 21262883Meneses J, Bhandari V, Alves JG, Herrmann D. Noninvasive ventilation for respiratory distress syndrome: a randomized controlled trial. Pediatrics. 2011 Feb;127(2):300-7. doi: 10.1542/peds.2010-0922. Epub 2011 Jan 24.
- Background: PubMed 23989138Roberts CT, Davis PG, Owen LS. Neonatal non-invasive respiratory support: synchronised NIPPV, non-synchronised NIPPV or bi-level CPAP: what is the evidence in 2013? Neonatology. 2013;104(3):203-9. doi: 10.1159/000353448. Epub 2013 Aug 28.
- Background: PubMed 23488612Ricotti A, Salvo V, Zimmermann LJ, Gavilanes AW, Barberi I, Lista G, Colivicchi M, Temporini F, Gazzolo D. N-SIPPV versus bi-level N-CPAP for early treatment of respiratory distress syndrome in preterm infants. J Matern Fetal Neonatal Med. 2013 Sep;26(13):1346-51. doi: 10.3109/14767058.2013.784255. Epub 2013 Apr 17.
- Derived from this study: PubMed 25667244Salvo V, Lista G, Lupo E, Ricotti A, Zimmermann LJ, Gavilanes AW, Barberi I, Colivicchi M, Temporini F, Gazzolo D. Noninvasive ventilation strategies for early treatment of RDS in preterm infants: an RCT. Pediatrics. 2015 Mar;135(3):444-51. doi: 10.1542/peds.2014-0895. Epub 2015 Feb 9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vincenzo V Salvo, MD principal investigator
Azienda Ospedaliera Universitaria Policlinico "G Martino" Messina
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing NSIPPV and BiPAP in people with RDS of Prematurity, run by Azienda Ospedaliera Universitaria Policlinico "G. Martino".
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Duration of NIV Support (time frame: 10 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02259400, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2015.