Sustained Lung Inflation in the Delivery Room in Preterm Infants at High Risk of Respiratory Distress Syndrome

Respiratory Distress Syndrome Clinical Trial

— SLIS  

Official title:

SLI STUDY: Sustained Lung Inflation in the Delivery Room in Preterm Infants at High Risk of Respiratory Distress Syndrome. A RCT Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01440868
• Other study ID #: 02-2011
• Status: Not yet recruiting
• Phase: N/A
• First received: September 16, 2011
• Last updated: September 26, 2011
• Start date: October 2011
• Est. completion date: September 2012

Study information

• Verified date: September 2011
• Source: University of Florence
• Contact: Carlo Dani, MD
• Phone: +39 055 7947428
• Email: cdani[@]unifi.it
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

BACKGROUND. Sustained lung inflation (SLI) associated to an adequate PEEP may help the efficacy of the respiratory effort in lung of preterm infants at risk for respiratory distress syndrome (RDS) and reduce need of mechanical ventilation (MV).

The investigators aim will be to demonstrate the hypothesis that the introduction of SLI in the delivery room protocol may reduce the need of MV in preterm infants.

STUDY DESIGN: Multicenter prospective randomized controlled trial. The study will be carried out at the neonatal care units of the Careggi Infants with a gestational age between 25 and 28 weeks will be eligible and randomized at birth to receive SLI or not. Peak inflation pressure (PIP) of 25 cm H2O will be delivered for 15 seconds and then reduced to a positive end expiratory pressure (PEEP) of 5 cm H2O.

Primary endpoint will be the need of MV within the first 72 hrs of life (excluding the transient tracheal intubation for surfactant replacement: e.g. INSURE). Population size: hypothesizing that SLI maneuver might decrease the need of MV during the first 72 hours of life from 35 to 20% the investigators calculated that 138 newborns must be enrolled in each groups to detect this difference statistically significant with 80% power at 0.05 level.

Description:

BACKGROUND Sustained lung inflation (SLI) applied at birth in the delivery room has been demonstrated to lead to clearance of lung fluid and achievement of a precocious functional residual capacity (FRC) both in animal and human studies. SLI associated to an adequate positive end expiratory pressure (PEEP) may help the efficacy of the respiratory effort in lung of preterm infants at risk for respiratory distress syndrome (RDS) and reduce need of mechanical ventilation (MV).

OBJECTIVES Our aim will be to demonstrate the hypothesis that the introduction of SLI in the delivery room protocol may reduce the need of MV in the first 72 hours of life in preterm infants at risk for RDS improving their respiratory outcome.

STUDY DESIGN This is a multicenter prospective randomized controlled trial. The study will be carried out at the neonatal care units of the Careggi University Hospital of Florence, the "V. Buzzi" Children Hospital of Milan, IRCCS Ospedale Maggiore Policlinico of Milan,the Catholic University of the Sacred Heart of Rome, the "S. Giovanni" Hospital of Rome, the Regional Hospital of Bozen, the Hospital of Varese, the the Sant'Anna University Hospital of Pisa, the "Maggiore" Hospital of Bologna, the "Di Venere" Hospital of Bari, the University Hospital of Foggia.

Inborn infants with a gestational age between 25 and 28 weeks will be eligible and randomized at birth in two groups. Group A: (SLI group) in this group the preterm infants will receive SLI with mask for initial alveolar recruitment using a pressure control system (Neopuff, Fisher & Paykel, Inc) in addition to American Academy of Pediatrics (AAP) guidelines for neonatal resuscitation. Peak inflation pressure (PIP) of 25 cm H2O will be delivered for 15 seconds and then reduced to a PEEP of 5 cm H2O. A second SLI manoeuvre will be repeated in case of persistent hearth failure (HR <100 bpm.Group B (control group: in this group the preterm infants will be resuscitated at birth according to AAP guidelines without SLI manoeuvre.

Infants in both the groups who will not be able to reach a good respiratory and/or cardiac effort, they will undergo tracheal intubation to start MV. Then, in neonatal intensive care unit (NICU), infants who will continue to breath spontaneously will be supported by nasal continuous positive airway pressure (NCPAP), bi-level positive airway pressure (BiPAP) or nasal intermittent mandatory ventilation (N-IMV) (PEEP at 5-7 cmH2O). Surfactant (Curosurf ®, Chiesi, Parma, Italia) will be administered (200 mg/kg) to newborns with FiO2 >0.40 or mechanically ventilated. MV will be started if blood pH <7.20, PCO2 >65 mm Hg, pO2 <50 mm Hg with a fraction of inspired oxygen (FiO2) >0.50 or in case of severe apnea; the objective of MV will be to maintain a PaCO2 45-65 mmHg and a PaO2 50-75 mmHg. Preterm infants will be extubated from MV when airway pressure will be <7 cmH2O, FiO2 <0.30, and in absence of severe apnea after caffeine therapy. After extubation it will be allowed to support infant with oxygen-therapy, NCPAP, BiPAP or N-IMV.

ENDPOINTS. Primary endpoint will be the need of MV within the first 72 hrs of life [(excluding the transient tracheal intubation for surfactant replacement: e.g. Intubation-SURfactant-Extubation (INSURE)]. Success criteria will be the lack of MV in the first 72 hrs of life. Secondary endpoints will be the occurrence of MV >3 hrs of life, length of MV and other non invasive respiratory supports (NCPAP/BiPAP/N-IMV), need of surfactant and number of doses, mortality, occurrence of bronchopulmonary dysplasia (BPD:oxygen-therapy at 36 post- conceptional age), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), retinopahty of prematurity (ROP) and necrotizing enterocolitis (NEC), sepsis, and length of NICU and hospital stay.

STATISTICAL ANALYSIS. Failure of treatment will be considered the need of MV during the first 72 hrs of life in both groups.

Population size: hypothesizing that SLI maneuver might decrease the need of MV during the first 72 hours of life from 35 to 20% we calculated that 138 newborns must be enrolled in each groups to detect this difference statistically significant with 80% power at 0.05 level.

Clinical characteristics of the two groups will be described by mean values and standard deviation, or median values and range, or by rate and percentage. The t-test, Wilcoxon rank-sum test, and Fisher's exact test will be used to compare continuous normally distributed data, nonparametric continuous data, and categorical data, respectively.

Multiple regression analysis will be performed to assess the possible influence of confounding variables (i.e.: gestational age, birth weight, etc.) on the primary endpoint predictive factors. Effect estimates will be expressed as relative risk (RR) with profile likelihood-based 95% confidence limits.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 276
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 15 Minutes

Eligibility

Inclusion Criteria:

• parental informed consent

• gestational age 25-28 weeks

Exclusion Criteria:

• fetal hydrops

• major congenital malformation

• inherited metabolic diseases

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Procedure:
• Sustained lung inflation
Sustained lung inflation (SLI) will be performed with mask using a pressure control system (Neopuff, Fisher & Paykel, Inc). Peak inflation pressure (PIP) of 25 cm H2O will be delivered for 15 seconds and then reduced to a PEEP of 5 cm H2O. A second SLI manoeuvre will be repeated in case of persistent hearth failure (HR <100 bpm ).

Locations

Country	Name	City	State
Italy	Department of Surgical and Medical Critical Care, Unversity of Florence	Florence

Sponsors (1)

Lead Sponsor	Collaborator
University of Florence

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Need of mechanical ventilation	Preterm infants are at risk of developing respiratory distress syndrome requiring mechanical ventilation. Sustained lung inflation in the delivery room might contribute to decrease the need of mechanical ventilation during the first 72 hrs of life because later other factors (i.e.: sepsis)than prematurity itself could induce this need.	First 72 hrs of life	No
Secondary	Complication rate	We will evaluate the occurrence of mechanical ventilation (MV) >3 hrs of life, length of MV and other non invasive respiratory supports, need of surfactant, mortality, the occurrence of the main prematurity complication such as bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) , periventricular leukomalacia (PVL), retinopathy of prematurity (ROP) and necrotizing enterocolitis (NEC), sepsis, and length of neonata intensive care (NICU) and hospital stay.	Participants will be followed for the duration of hospital stay, an expected average of 13 weeks	Yes