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Trial registered on ANZCTR


Registration number
ACTRN12618001638224p
Ethics application status
Submitted, not yet approved
Date submitted
25/09/2018
Date registered
3/10/2018
Date last updated
3/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
In extremely preterm infants less than 28 weeks gestation who are receiving invasive mechanical ventilation, does extubation to a higher level of continuous positive airway pressure compared to standard practice prevent deterioration and return to mechanical ventilation.
Scientific title
A multicentre randomised control trial comparing high (9-11 cmH2O) vs. standard (6-8 cmH2O) Continuous Positive Airway Pressures after Extubation in Extremely Preterm Infants to reduce extubation failure.
Secondary ID [1] 295961 0
None
Universal Trial Number (UTN)
U1111-1219-7280
Trial acronym
Extubation CPAP Level Assessment trial (ÉCLAT).
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Extreme Prematurity 309468 0
Respiratory Distress Syndrome 309469 0
Extubation Failure 309470 0
Condition category
Condition code
Reproductive Health and Childbirth 308305 308305 0 0
Complications of newborn
Respiratory 308663 308663 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Infants will be extubated to a set Continuous Positive Airway Pressure (CPAP) level of 10 cm H2O. Whilst receiving CPAP, infants will remain within the set CPAP levels range of 9 cm H2O – 11 cm H2O for at least 24 hours, with changes to the set CPAP levels within this range at the discretion of the treating team. After 24 hours, infants may have their set CPAP level weaned at the discretion of the treating team, but must remain within a set CPAP level range 5 cm H2O – 11 cm H2O for at least 7 days after extubation if receiving CPAP. Infants will be re-intubated if they satisfy extubation failure criteria within 7 days after extubation, defined as: FiO2 requirement >0.20 above the pre-extubation FiO2, Two or more apnoeic episodes within any 24-hour period requiring intermittent positive pressure ventilation, or six or more apneoic events requiring stimulation in any 6-hour period, Respiratory acidosis with pH <7.2 and CO2 >60 mm Hg or urgent intubation for an acute deterioration. The fraction of inspired oxygen will be titrated to keep oxygen saturations in the standard target ranges of the enrolling hospital. Adherence to the study protocol will be monitored both by direct observation by study personnel as well as auditing of the individual medical records.
Intervention code [1] 312287 0
Treatment: Other
Comparator / control treatment
Control arm:
Infants will be extubated to a set CPAP pressure of 7 cm H2O. Whilst receiving CPAP, infants will remain within a set CPAP pressure range of 6 cm H2O – 8 cm H2O for at least 24 hours, with changes to the set CPAP pressure within this range at the discretion of the treating team. After 24 hours, infants may have their set CPAP pressure weaned at the discretion of the treating team, but must remain within a set CPAP pressure range 5 cm H2O – 8 cm H2O for at least 7 days after extubation if receiving CPAP. Infants will be re-intubated if they satisfy the extubation failure criteria described below within 7 days after extubation. The FiO2 will be titrated to keep SpO2 in the standard target ranges of the enrolling hospital.
Control group
Active

Outcomes
Primary outcome [1] 307279 0
Extubation failure defined as:
1. Fraction of inspired oxygen requirement >0.20 above the pre-extubation fraction of inspired oxygen,
2. Two or more apnoeic episodes within any 24-hour period requiring intermittent positive pressure ventilation, or six or more apneoic events requiring stimulation in any 6-hour period,
3. Respiratory acidosis with pH <7.2 and CO2 >60 mm Hg
4. Urgent intubation for an acute deterioration with the reason for re-intubation documented.
Timepoint [1] 307279 0
7 days POST extubation.
Secondary outcome [1] 351353 0
Death before hospital discharge: Assessed by data-linkage of medical records,
Timepoint [1] 351353 0
Death or discharge from hospital
Secondary outcome [2] 352397 0
Duration of mechanical ventilation in days after randomisation in survivors: Assessed by data-linkage of medical records,
Timepoint [2] 352397 0
Death or discharge from hospital
Secondary outcome [3] 352398 0
Total duration of hospitalisation in days in survivors: Assessed by data-linkage of medical records,
Timepoint [3] 352398 0
Discharge from hospital
Secondary outcome [4] 352399 0
Incidence of re-intubation within 72 hours and within 96 hours: Assessed by data-linkage of medical records.
Timepoint [4] 352399 0
Assessed at 72 hours and 96 hours.
Secondary outcome [5] 352400 0
Timing of extubation failure (if applicable) in hours after extubation: Assessed by data-linkage to medical records
Timepoint [5] 352400 0
Up to 7 days post extubation
Secondary outcome [6] 352401 0
Reason for re-intubation(s) (if applicable): Assessed by data-linkage to medical records
Timepoint [6] 352401 0
At time of re-intubation
Secondary outcome [7] 352402 0
Postmenstrual age at last supplemental oxygen : Assessed by data-linkage to medical records
Timepoint [7] 352402 0
Death or discharge from hospital
Secondary outcome [8] 352403 0
Incidence of treatment with postnatal corticosteroids for lung disease after randomisation: ASsessed by data-linkage to medical records
Timepoint [8] 352403 0
Death or discharge from hospital
Secondary outcome [9] 352404 0
Incidence of air leaks from the lung requiring drainage with thoracocentesis or intercostal catheter insertion: Assessed by data-linkage to medical records
Timepoint [9] 352404 0
Death or discharge from hospital
Secondary outcome [10] 352405 0
Incidence of radiologically-diagnosed pulmonary interstitial emphysema after randomisation: Assessed by data-linkage to medical records
Timepoint [10] 352405 0
Death or discharge from hospital
Secondary outcome [11] 352406 0
Incidence of bronchopulmonary dysplasia (BPD), defined as a requirement for supplemental oxygen and/or respiratory support at 36 weeks’ post-menstrual age: Assessed by data-linkage to medical records
Timepoint [11] 352406 0
Death, discharge from hospital or 36 weeks’ postmenstrual age if still an inpatient in hospital.
Secondary outcome [12] 352407 0
Incidence of necrotising enterocolitis Bell’s stage 2 or above after randomisation: Assessed by data-linkage to medical records
Timepoint [12] 352407 0
Death or discharge from hospital
Secondary outcome [13] 352408 0
Incidence of spontaneous intestinal perforation after randomisation: Assessed by data-linkage to medical records
Timepoint [13] 352408 0
Death or discharge from hospital
Secondary outcome [14] 352409 0
Incidence of retinopathy of prematurity requiring treatment with laser therapy or medication in one or both eyes after randomisation: Assessed by data-linkage to medical records
Timepoint [14] 352409 0
Death or discharge from hospital
Secondary outcome [15] 352410 0
Incidence of new diagnosis of grade 3 or 4 intraventricular haemorrhage after randomisation: Assessed by data-linkage to medical records
Timepoint [15] 352410 0
Death or discharge from hospital
Secondary outcome [16] 352441 0
Postmenstrual age at last positive pressure ventilation (any or Mechanica Ventilation/CPAP/Highflow): Assessed by data-linkage to medical records
Timepoint [16] 352441 0
Death or hospital discharge

Eligibility
Key inclusion criteria
1. are born less than 28 weeks’ gestation
2. are being extubated for the first time from mechanical ventilation to nasal CPAP
3. have received enteral or intravenous caffeine within 24 hours prior to the planned extubation
4. have received surfactant
Minimum age
No limit
Maximum age
36 Weeks
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Are being extubated to any other mode of non-invasive respiratory support other than CPAP, or to no respiratory support
2. Have a major congenital anomaly or condition that might have an adverse effect on breathing or ventilation: known upper airway obstruction or major airway abnormality, or major congenital heart disease
3. Are 36 weeks or greater corrected age at time of extubation
4. Are not receiving full intensive care after extubation

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Infants will be randomised using sequentially numbered, sealed, opaque envelopes. These will be prepared by the study statistician using variable block sizes. Only the first extubation will be randomised. Multiple births will be randomised individually. Randomisation will occur after the clinical decision to extubate has been made and shortly before extubation.

Stratification will be by centre and gestational age at birth (less than 26 weeks; greater than or equal to 26 weeks).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Statistical analysis will be performed on an intention-to-treat basis. Continuous variables will be compared using t-tests or Mann Whitney U-tests as appropriate; categorical variables will be compared using chi-squared or Fisher’s Exact tests. A subgroup analyses by gestational age at birth is planned for the primary outcome. A Kaplan Meier analysis of the timing of extubation failure in both groups will be performed.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 11753 0
The Royal Women's Hospital - Parkville
Recruitment hospital [2] 11754 0
Monash Children’s Hospital - Clayton
Recruitment postcode(s) [1] 23839 0
3052 - Parkville
Recruitment postcode(s) [2] 23840 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 300559 0
Self funded/Unfunded
Name [1] 300559 0
unfunded
Address [1] 300559 0
unfunded
Country [1] 300559 0
Primary sponsor type
Individual
Name
Anna M Kidman
Address
University of Melbourne
Faculty of Medicine
Department of Obstetrics and Gynaecology
Newborn Research – Level 7 Royal Women’s Hospital
Grattan St & Flemington Rd
Parkville VIC 3052 AUSTRALIA
Country
Australia
Secondary sponsor category [1] 300360 0
None
Name [1] 300360 0
Address [1] 300360 0
Country [1] 300360 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 301351 0
The Monash Health Human Research Ethics Committee (HREC)
Ethics committee address [1] 301351 0
Research Support Services
Level 2, i Block,
Monash Medical Centre
246 Clayton Road
CLAYTON VIC 3168
T: 613 9594 4611
F: 613 9594 6306
Ethics committee country [1] 301351 0
Australia
Date submitted for ethics approval [1] 301351 0
19/09/2018
Approval date [1] 301351 0
Ethics approval number [1] 301351 0

Summary
Brief summary
Does extubation to a higher CPAP pressure decrease risk of extubation failure following the first extubation attempt within the first 3 weeks of birth compared with CPAP pressure currently used?
This study will explore the effects of higher nCPAP pressure versus standard CPAP pressure on the need for re-intubation through a randomised clinical trial. This study will involve 200 extremely preterm infants born less than 28 weeks’ gestation who are being extubated. They will be extubated to either the high group of CPAP (10 cm H2O) compared with a standard practice. The hypothesis is that higher levels of nCPAP will reduce extubation failure in the extreme preterm infant.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 86706 0
Miss Anna Kidman
Address 86706 0
University of Melbourne
Faculty of Medicine
Department of Obstetrics and Gynaecology
Newborn Research – Level 7 Royal Women’s Hospital
Grattan St & Flemington Rd
Parkville VIC 3052 AUSTRALIA
Country 86706 0
Australia
Phone 86706 0
+61 4 238 161 97
Fax 86706 0
Email 86706 0
a.kidman@student.unimelb.edu.au
Contact person for public queries
Name 86707 0
Miss Anna Kidman
Address 86707 0
University of Melbourne
Faculty of Medicine
Department of Obstetrics and Gynaecology
Newborn Research – Level 7 Royal Women’s Hospital
Grattan St & Flemington Rd
Parkville VIC 3052 AUSTRALIA
Country 86707 0
Australia
Phone 86707 0
+61 4 238 161 97
Fax 86707 0
Email 86707 0
a.kidman@student.unimelb.edu.au
Contact person for scientific queries
Name 86708 0
Miss Anna Kidman
Address 86708 0
University of Melbourne
Faculty of Medicine
Department of Obstetrics and Gynaecology
Newborn Research – Level 7 Royal Women’s Hospital
Grattan St & Flemington Rd
Parkville VIC 3052 AUSTRALIA
Country 86708 0
Australia
Phone 86708 0
+61 4 238 161 97
Fax 86708 0
Email 86708 0
a.kidman@student.unimelb.edu.au

No data has been provided for results reporting
Summary results
Not applicable