Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611000916943
Ethics application status
Approved
Date submitted
25/08/2011
Date registered
26/08/2011
Date last updated
2/12/2022
Date data sharing statement initially provided
17/09/2020
Date results information initially provided
17/09/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Multicentre randomised controlled trial of minimally-invasive surfactant therapy in preterm infants 25-28 weeks gestation on continuous positive airway pressure
Scientific title
Multicentre randomised controlled trial in preterm infants 25-28 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 incidence of the composite outcome of death or physiological BPD.
Secondary ID [1] 259787 0
Nil
Universal Trial Number (UTN)
Trial acronym
OPTIMIST-A
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neonatal respiratory distress syndrome 261372 0
Bronchopulmonary dysplasia 261373 0
Condition category
Condition code
Respiratory 259529 259529 0 0
Other respiratory disorders / diseases
Reproductive Health and Childbirth 270823 270823 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 poractant surfactant dose will be 200 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 6 hours of life.

This intervention will be given throughout the course of the trial, which is expected to last 5 years.
Intervention code [1] 264224 0
Treatment: Drugs
Intervention code [2] 269278 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 intubation equipment, screening the baby, testing suction unit, repositioning of the baby and changing the baby's monitoring.
Control group
Placebo

Outcomes
Primary outcome [1] 262337 0
Composite outcome of death by 36 weeks or physiological bronchopulmonary dysplasia (BPD). Physiological BPD is assessed at 36 weeks post-menstrual age, and is defined as either need for respiratory support (intubation / CPAP / high flow nasal cannula > 2 L/min) or need for FiO2 >=0.3 or failure of a room air trial conducted at 36 weeks post-menstrual age. This will be assessed by the research nurse at each centre.
Timepoint [1] 262337 0
36 weeks post-menstrual age
Secondary outcome [1] 273563 0
Mortality
Timepoint [1] 273563 0
By 36 weeks post-menstrual age and throughout hospitalisation.
Secondary outcome [2] 273564 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] 273564 0
During first hospitalisation
Secondary outcome [3] 273565 0
Pneumothorax, as documented in medical record.
Timepoint [3] 273565 0
During first hospitalisation
Secondary outcome [4] 273566 0
Duration of respiratory support, defined as cumulative hours of all episodes of intubation, nasal CPAP and high flow nasal cannula oxygen (flow rate >= 2 litres/min). This information will be derived from medical record or unit database.
Timepoint [4] 273566 0
During first hospitalisation

Eligibility
Key inclusion criteria
1. Gestational age 25-28 completed weeks 2. Requiring CPAP with signs of early respiratory distress. 3. CPAP pressure of 5-8 cm H2O and FiO2 >=0.30. 4. Less than 6 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
6 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 25 weeks 0 days - 28 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. There will be two gestational age strata; 25-26 weeks and 27-28 weeks.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
OPTIMIST-A statistical analysis plan uploaded on 3rd November 2020.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
Other reasons/comments
Other reasons
COVID-19 forced many of our sites to cease recruitment for foreseeable future. Funding to cease from end of 2020.
Date of first participant enrolment
Anticipated
21/11/2011
Actual
16/12/2011
Date of last participant enrolment
Anticipated
Actual
20/03/2020
Date of last data collection
Anticipated
31/08/2022
Actual
Sample size
Target
606
Accrual to date
Final
486
Recruitment in Australia
Recruitment state(s)
ACT,QLD,TAS,VIC
Recruitment hospital [1] 4591 0
Royal Hobart Hospital - Hobart
Recruitment hospital [2] 4592 0
The Royal Women's Hospital - Parkville
Recruitment hospital [3] 4593 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [4] 4594 0
Mercy Hospital for Women - Heidelberg
Recruitment hospital [5] 17551 0
The Canberra Hospital - Garran
Recruitment hospital [6] 17552 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 31286 0
2605 - Garran
Recruitment postcode(s) [2] 12198 0
3052 - Parkville
Recruitment postcode(s) [3] 12200 0
3081 - Heidelberg Rgh
Recruitment postcode(s) [4] 12199 0
3168 - Clayton
Recruitment postcode(s) [5] 31287 0
4029 - Herston
Recruitment postcode(s) [6] 12197 0
7000 - Hobart
Recruitment outside Australia
Country [1] 7302 0
United States of America
State/province [1] 7302 0
Illinois
Country [2] 7303 0
New Zealand
State/province [2] 7303 0
Auckland
Country [3] 7304 0
United States of America
State/province [3] 7304 0
Connecticut
Country [4] 7305 0
United States of America
State/province [4] 7305 0
Hawaii
Country [5] 7306 0
United States of America
State/province [5] 7306 0
California
Country [6] 7307 0
United States of America
State/province [6] 7307 0
New Jersey
Country [7] 7308 0
United States of America
State/province [7] 7308 0
West Virginia
Country [8] 7309 0
Turkey
State/province [8] 7309 0
Ankara
Country [9] 7310 0
Turkey
State/province [9] 7310 0
Bursa
Country [10] 7311 0
Israel
State/province [10] 7311 0
Tsfat
Country [11] 7312 0
Slovenia
State/province [11] 7312 0
Country [12] 7313 0
New Zealand
State/province [12] 7313 0
Otago
Country [13] 22994 0
Canada
State/province [13] 22994 0
Edmonton
Country [14] 22995 0
Qatar
State/province [14] 22995 0
Doha

Funding & Sponsors
Funding source category [1] 264670 0
Charities/Societies/Foundations
Name [1] 264670 0
Royal Hobart Hospital Research Foundation
Country [1] 264670 0
Australia
Funding source category [2] 286253 0
Government body
Name [2] 286253 0
National Health and Medical Research Council
Country [2] 286253 0
Australia
Primary sponsor type
University
Name
Menzies Institute of Medical Research University of Tasamania
Address
Liverpool St
Hobart
TAS 7000
Country
Australia
Secondary sponsor category [1] 266570 0
University
Name [1] 266570 0
University of Tasmania
Address [1] 266570 0
Sandy Bay
TAS 7005
Country [1] 266570 0
Australia
Other collaborator category [1] 251875 0
Hospital
Name [1] 251875 0
Royal Hobart Hospital
Address [1] 251875 0
Liverpool St
Hobart
TAS 7000
Country [1] 251875 0
Australia
Other collaborator category [2] 252137 0
Hospital
Name [2] 252137 0
Royal Women's Hospital
Address [2] 252137 0
Flemington Rd
Parkville
VIC 3052
Country [2] 252137 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269555 0
Tasmanian Human Research Ethics Committee
Ethics committee address [1] 269555 0
Office of Research Services
University of Tasmania
Private Bag 1
Hobart
Tasmania
7001
Ethics committee country [1] 269555 0
Australia
Date submitted for ethics approval [1] 269555 0
Approval date [1] 269555 0
06/06/2011
Ethics approval number [1] 269555 0
H11615
Ethics committee name [2] 293819 0
Royal Women's Hospital Research Committee
Ethics committee address [2] 293819 0
Flemington Road
Parkville
Victoria 3052
Ethics committee country [2] 293819 0
Australia
Date submitted for ethics approval [2] 293819 0
Approval date [2] 293819 0
17/08/2011
Ethics approval number [2] 293819 0
11/39
Ethics committee name [3] 293820 0
Monash Health HREC B
Ethics committee address [3] 293820 0
Monash Health
Monash Medical Centre
246 Clayton Road
Clayton
Victoria 3168
Ethics committee country [3] 293820 0
Australia
Date submitted for ethics approval [3] 293820 0
17/10/2013
Approval date [3] 293820 0
23/12/2013
Ethics approval number [3] 293820 0
13362B
Ethics committee name [4] 293821 0
Mercy Health Human Research Ethics Committee
Ethics committee address [4] 293821 0
Mercy Health
Level 2, 12 Shelley St.,
Richmond
Victoria 3121
Ethics committee country [4] 293821 0
Australia
Date submitted for ethics approval [4] 293821 0
01/03/2013
Approval date [4] 293821 0
31/03/2013
Ethics approval number [4] 293821 0
R13/10
Ethics committee name [5] 293822 0
Auckland District Health Board Research Review Committee
Ethics committee address [5] 293822 0
Auckland City Hospital
PB 92024
Grafton
Auckland
Ethics committee country [5] 293822 0
New Zealand
Date submitted for ethics approval [5] 293822 0
Approval date [5] 293822 0
04/04/2014
Ethics approval number [5] 293822 0
13/NTB/126
Ethics committee name [6] 293823 0
NorthShore University HealthSystem First Friday Institutional Review Board
Ethics committee address [6] 293823 0
1001 University Place
Evanston
IL 60201
Ethics committee country [6] 293823 0
United States of America
Date submitted for ethics approval [6] 293823 0
12/07/2012
Approval date [6] 293823 0
12/06/2013
Ethics approval number [6] 293823 0
EH 13-047
Ethics committee name [7] 293824 0
The Cooper Health System Institutional Review Board
Ethics committee address [7] 293824 0
E&R Building rooms 128 and 288
401 Haddon Ave.,
Camden
New Jersey 08103
Ethics committee country [7] 293824 0
United States of America
Date submitted for ethics approval [7] 293824 0
Approval date [7] 293824 0
04/04/2015
Ethics approval number [7] 293824 0
RP# 13-033
Ethics committee name [8] 293825 0
Western Institutional Review Board
Ethics committee address [8] 293825 0
1019 39th Ave., SE Suite 120
Puyallup
WA 98374-2115
Ethics committee country [8] 293825 0
United States of America
Date submitted for ethics approval [8] 293825 0
Approval date [8] 293825 0
06/10/2014
Ethics approval number [8] 293825 0
1147151
Ethics committee name [9] 293826 0
Clinical Trials Department Ministry of Health
Ethics committee address [9] 293826 0
PO B1176
Jerusalem 9101002
Ethics committee country [9] 293826 0
Israel
Date submitted for ethics approval [9] 293826 0
Approval date [9] 293826 0
20/11/2014
Ethics approval number [9] 293826 0
20140110

Summary
Brief summary
Does administration of exogenous surfactant using a minimally-invasive technique improve outcome in preterm infants 25-28 weeks gestation treated with continuous positive airway pressure (CPAP)? A multicentre, randomised, masked, controlled trial will be conducted in inborn preterm infants 25-28 weeks gestation, aged less than 6 hours, requiring CPAP because of respiratory distress, with an FiO2 of >=0.3 and CPAP pressure 5-8. Infants randomised to surfactant treatment will receive 200 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 incidence of death or BPD. Secondary outcomes will include incidence of death, major neonatal morbidities (BPD, intraventricular haemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotising enterocolitis), pneumothorax and patent ductus arteriosus; need for intubation and surfactant therapy; durations of mechanical respiratory support, intubation, CPAP, intubation and CPAP, high flow nasal cannula (HFNC), oxygen therapy, intensive care stay and hospitalisation; hospitalisation cost; applicability and safety of the MIST procedure; and outcome at 2 years. The sample size will be 303/group, allowing detection of a 33% difference in the primary outcome with 90% power. The trial commenced at Royal Hobart Hospital December 2011 and Royal Women's Hospital during 2012, and will ultimately be conducted over 7 years in multiple centres nationally and overseas. Followup: at 2 years corrected age, parents of each infant will complete a brief health assessment and a validated child development assessment (PARCA-R, Dev Med Child Neurol 2004;46:389–97) administered as a web-based questionnaire located on a secure server. No identifying details will be revealed in the completion of the questionnaire. Health information to be collected will include duration of oxygen therapy at home, details of hospitalisations in the first 2 years (age, duration and classification of illness [respiratory/non-respiratory]), whether immunized against respiratory syncytial virus and influenza, family history of asthma, details of respiratory symptoms (respiratory distress and wheezing) and medications, details of feeding, vision and hearing capabilities, and presence and severity of motor problems. The PARCA-R questionnaire will seek information on the child’s development and speech.
Trial website
http://www.menzies.utas.edu.au/optimist-trials
Trial related presentations / publications
Dargaville PA, Aiyappan A, De Paoli AG, et al. Minimally-invasive surfactant therapy in preterm infants on continuous positive airway pressure. Arch Dis Child Fetal Neonatal Ed 2012; doi: 10.1136/archdischild-2011-301314

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-F248.

Dargaville PA, Aiyappan A, De Paoli AG, et al. CPAP failure in preterm infants defines a group at high risk of adverse outcome. PAS abstract 2011; 752879

Dargaville PA. Innovation in Surfactant Therapy I: Surfactant Lavage and Surfactant Administration by Fluid Bolus Using Minimally Invasive Techniques. Neonatology 2012;101: 326-336
Public notes

Contacts
Principal investigator
Name 32346 0
Prof Peter Dargaville
Address 32346 0
Royal Hobart Hospital
Liverpool Street
Hobart
Tasmania
7000
Country 32346 0
Australia
Phone 32346 0
+61 3 61667546
Fax 32346 0
Email 32346 0
peter.dargaville@dhhs.tas.gov.au
Contact person for public queries
Name 15593 0
Prof Peter Dargaville
Address 15593 0
Royal Hobart Hospital
Liverpool St
Hobart
TAS 7000
Country 15593 0
Australia
Phone 15593 0
+61 3 61667546
Fax 15593 0
Email 15593 0
peter.dargaville@dhhs.tas.gov.au
Contact person for scientific queries
Name 6521 0
Prof Peter Dargaville
Address 6521 0
Royal Hobart Hospital
Liverpool St
Hobart
TAS 7000
Country 6521 0
Australia
Phone 6521 0
+61 3 61667546
Fax 6521 0
Email 6521 0
peter.dargaville@dhhs.tas.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not yet agreed by Trial Steering Committee


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
11937Statistical analysis plan    336668-(Uploaded-03-11-2020-20-31-08)-Study-related document.pdf
11938Study protocol https://bmcpediatr.biomedcentral.com/track/pdf/10.1186/1471-2431-14-213.pdf 
17771Statistical analysis plan    Statistical analysis plan for the OPTIMIST-2 study... [More Details] 336668-(Uploaded-25-11-2022-11-04-44)-Study-related document.pdf


Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Dargaville PA, Kamlin COF, Orsini F, Wang X, De Pa... [More Details] 336668-(Uploaded-25-11-2022-11-01-28)-Journal results publication.pdf

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEffect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants with Respiratory Distress Syndrome: The OPTIMIST-A Randomized Clinical Trial.2021https://dx.doi.org/10.1001/jama.2021.21892
EmbaseSuccess of blinding a procedural intervention in a randomised controlled trial in preterm infants receiving respiratory support.2023https://dx.doi.org/10.1177/17407745231171647
Dimensions AIThe OPTIMIST-A trial: evaluation of minimally-invasive surfactant therapy in preterm infants 25–28 weeks gestation2014https://doi.org/10.1186/1471-2431-14-213
Dimensions AITwo-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants2023https://doi.org/10.1001/jama.2023.15694
N.B. These documents automatically identified may not have been verified by the study sponsor.