Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611000917932
Ethics application status
Approved
Date submitted
25/08/2011
Date registered
26/08/2011
Date last updated
11/11/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Multicentre randomised controlled trial of minimally-invasive surfactant therapy in preterm infants 29-32 weeks gestation on continuous positive airway pressure
Scientific title
Multicentre randomised controlled trial in preterm infants 29-32 weeks gestation on continuous positive airway pressure of the effect of minimally-invasive surfactant therapy in comparison to standard care (continuation of CPAP) on the duration of respiratory support (all hours of intubation, nasal CPAP and high flow nasal cannula).
Secondary ID [1] 262788 0
nil
Universal Trial Number (UTN)
Trial acronym
OPTIMIST-B
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neonatal respiratory distress syndrome 270495 0
Condition category
Condition code
Respiratory 270654 270654 0 0
Other respiratory disorders / diseases
Reproductive Health and Childbirth 270825 270825 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Minimally invasive surfactant therapy - delivery of exogenous surfactant to the lung via brief catheterisation of the trachea with an instillation catheter in a preterm infant who is being supported with continuous positive airway pressure (CPAP) via nasal prongs or mask. The surfactant dose will be 100 mg/kg, administered over 15 - 30 seconds. Total duration of the procedure will be less than 5 minutes, followed by reinstitution of CPAP. Only a single dose will be given within the first 12 hours of life.
Intervention code [1] 269133 0
Treatment: Drugs
Intervention code [2] 269280 0
Treatment: Devices
Comparator / control treatment
Continued treatment with nasal CPAP delivered by prongs or mask. This is the standard control treatment. After randomisation, infants will receive a sham treatment from a treatment team not engaged in clinical care. This will not involve removal of prongs or discontinuation of CPAP but will require setting up equipment, screening baby, repositioning baby, use of suctioning equipment and change of monitoring.
Control group
Placebo

Outcomes
Primary outcome [1] 269374 0
Duration of respiratory support, including all hours of intubation, nasal CPAP and high flow nasal cannula support (flow rate > 2 L/min). This will be assessed by the research nurse at each centre.
Timepoint [1] 269374 0
During first hospitalisation
Secondary outcome [1] 279496 0
Mortality
Timepoint [1] 279496 0
During first hospitalisation
Secondary outcome [2] 279497 0
Major morbidity, defined as one or more of BPD, grade III or IV intraventricular haemorrhage, periventricular leukomalacia or retinopathy of prematurity > stage 2. Screening for intraventricular haemorrhage, periventricular leukomalacia and retinopathy of prematurity will be performed as routine care, and the results taken from the medical record.
Timepoint [2] 279497 0
During first hospitalisation
Secondary outcome [3] 279498 0
Pneumothorax, as documented in medical record
Timepoint [3] 279498 0
During first hospitalisation
Secondary outcome [4] 279499 0
Cost of hospitalisation assessed by computation of length of stay and level of acuity.
Timepoint [4] 279499 0
During first hospitalisation

Eligibility
Key inclusion criteria
1. Gestational age 29-32 completed weeks
2. Requiring CPAP with signs of early respiratory distress.
3. CPAP pressure of 5-6 cm H2O and FiO2 >=0.32, or a CPAP pressure 7-8 cm H2O and FiO2 >=0.28.
4. Less than 12 hours of age.
5. Agreement of the Treating Physician in charge of the infant’s care.
6. Signed parental consent.
Minimum age
0 Hours
Maximum age
12 Hours
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previously intubated, or in imminent need of intubation because of respiratory distress, apnoea or persistent acidosis.
2. Congenital anomaly or condition that might adversely affect breathing.
3. Identifiable alternative cause for respiratory distress (e.g. congenital pneumonia or pulmonary hypoplasia).
4. Lack of availability of an OPTIMIST treatment team.

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)
Preterm infants of gestation 29 weeks 0 days - 32 weeks 6 days who fulfill the entry criteria will be enrolled once written parental consent has been obtained by the treating clinicians. The infant will be randomised by the OPTIMIST Treatment Team, after handover of care from the treating clinicians. A web-based central randomisation program will allocate infants into “surfactant via MIST” and “standard care” groups, with an allocation ratio of 1:1. Twins and higher order multiples will be randomised independently.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation schedule and web-based
service will be provided by the Clinical Epidemiology and Biostatistics Unit at the Murdoch Childrens Research Institute. The randomisation will be in randomly permuted blocks of variable length, stratified by study centre, and by gestational age. For each trial there will be two gestational
age strata 29-30 weeks and 31-32 weeks.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/01/2017
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
454
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 269609 0
Charities/Societies/Foundations
Name [1] 269609 0
Royal Hobart Hospital Research Foundation
Country [1] 269609 0
Australia
Primary sponsor type
University
Name
Menzies Institute of Medical Research, University of Tasmania
Address
17 Liverpool Street
Hobart TAS 7000
Country
Australia
Secondary sponsor category [1] 266642 0
University
Name [1] 266642 0
University of Tasmania
Address [1] 266642 0
Sandy Bay Rd.,
Sandy Bay
Hobart TAS 7005
Country [1] 266642 0
Australia
Other collaborator category [1] 252177 0
Hospital
Name [1] 252177 0
Royal Hobart Hospital
Address [1] 252177 0
Liverpool St
Hobart TAS 7000
Country [1] 252177 0
Australia
Other collaborator category [2] 252178 0
Hospital
Name [2] 252178 0
Royal Women's Hospital
Address [2] 252178 0
Flemington Rd.,
Parkville
VIC 3052
Country [2] 252178 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269557 0
Tasmanian Human Research Ethics Committee
Ethics committee address [1] 269557 0
Office of Research Services
University of Tasmania
Private Bag 1
Hobart
Tasmania
7001
Ethics committee country [1] 269557 0
Australia
Date submitted for ethics approval [1] 269557 0
Approval date [1] 269557 0
06/06/2011
Ethics approval number [1] 269557 0
H11616

Summary
Brief summary
Research question: Does administration of exogenous surfactant using a minimally-invasive technique improve outcome in preterm infants 29-32 weeks gestation treated with continuous positive airway pressure (CPAP)?

A multicentre, randomised, masked, controlled trial will be conducted in preterm infants 29-32 weeks gestation, aged less than 12 hours, requiring CPAP because of respiratory distress, with an FiO2 of >=0.32 (CPAP pressure 5-6) or >=0.28 (CPAP pressure 7-8). Infants randomised to surfactant treatment will receive 100 mg/kg of poractant alfa (Curosurf) administered under direct laryngoscopy using a surfactant instillation catheter, followed by reinstitution of CPAP. Controls will continue on CPAP. The intervention will be masked from the clinical team.

Care thereafter will be as per usual in both groups, other than the requirement to adhere to intubation criteria. The primary outcome will be duration of respiratory support (all hours of intubation, CPAP and high flow nasal cannula). Secondary outcomes will include Need for intubation and surfactant therapy; durations of intubation, CPAP, intubation and CPAP, HFNC, oxygen therapy, intensive care stay and hospitalisation; hospitalisation cost; incidence of death, major neonatal morbidities, pneumothorax and patent ductus arteriosus; and applicability and safety of the MIST procedure.

The sample size will be 227/group, allowing detection of a 25% reduction in duration of respiratory support with 90% power.

The trial will commence at Royal Hobart Hospital and Royal Women's Hospital during 2011, and will ultimately be conducted over 5 years in multiple centres nationally and overseas.
Trial website
Trial related presentations / publications
Dargaville PA, Aiyappan A, De Paoli AG, et al. CPAP failure in preterm infants defines a group at high risk of adverse outcome (abstract). E-PAS 2011: 4529.412.

Dargaville PA, Aiyappan A, De Paoli AG, et al. Minimally invasive surfactant therapy in preterm infants on CPAP (abstract). E-PAS 2011: 4530.430.

Dargaville PA, Aiyappan A, Cornelius A, et al. Preliminary evaluation of a new technique of minimally invasive surfactant therapy. Arch Dis Child Fetal Neonatal Ed 2011; 96: F243-8.
Public notes

Contacts
Principal investigator
Name 32983 0
Prof Peter Dargaville
Address 32983 0
Department of Paediatrics
Royal Hobart Hospital
Liverpool St.,
Hobart
Tasmania 7000
Country 32983 0
Australia
Phone 32983 0
+61 3 62228308
Fax 32983 0
Email 32983 0
[email protected]
Contact person for public queries
Name 16230 0
Prof Peter Dargaville
Address 16230 0
Royal Hobart Hospital
Liverpool St
Hobart
TAS 7000
Country 16230 0
Australia
Phone 16230 0
+61 3 62227546
Fax 16230 0
Email 16230 0
[email protected]
Contact person for scientific queries
Name 7158 0
Prof Peter Dargaville
Address 7158 0
Royal Hobart Hospital
Liverpool St
Hobart
TAS 7000
Country 7158 0
Australia
Phone 7158 0
+61 3 62227546
Fax 7158 0
Email 7158 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
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