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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02140580




Registration number
NCT02140580
Ethics application status
Date submitted
13/05/2014
Date registered
16/05/2014
Date last updated
1/05/2020

Titles & IDs
Public title
OPTIMIST-A Trial: Minimally-invasive Surfactant Therapy in Preterm Infants 25-28 Weeks Gestation on CPAP
Scientific title
Multicentre Randomised Controlled Trial of Minimally-invasive Surfactant Therapy in Preterm Infants 25-28 Weeks Gestation on Continuous Positive Airways Pressure
Secondary ID [1] 0 0
4.3, 6th June 2013
Universal Trial Number (UTN)
Trial acronym
OPTIMIST-A
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bronchopulmonary Dysplasia 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Reproductive Health and Childbirth 0 0 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - Minimally invasive surfactant therapy
Other interventions - Continuation on CPAP

Active Comparator: Minimally invasive surfactant therapy - 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. Poractant alfa (Curosurf) at a dosage of 200 mg/kg will be administered over 15 - 30 seconds. Total duration of the procedure will be less than 5 minutes, followed by reinstitution of CPAP.

Sham Comparator: Continuation on CPAP - 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. CPAP will thereafter continue.


Treatment: Devices: Minimally invasive surfactant therapy
Active Comparator

Other interventions: Continuation on CPAP
Sham Comparator

Intervention code [1] 0 0
Treatment: Devices
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Death or physiological bronchopulmonary dysplasia - 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] 0 0
36 weeks post menstrual age
Secondary outcome [1] 0 0
Mortality
Timepoint [1] 0 0
36 weeks post menstrual age
Secondary outcome [2] 0 0
Major morbidity - Major morbidity, defined as one or more of BPD, grade III or IV intraventricular haemorrhage, periventricular leukomalacia or retinopathy of prematurity > stage 2, occurring at any time up to 36 weeks post menstrual age. 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] 0 0
36 weeks post menstrual age
Secondary outcome [3] 0 0
Pneumothorax - Pneumothorax at any time up to 36 weeks post menstrual age, as documented in medical record.
Timepoint [3] 0 0
36 weeks post menstrual age
Secondary outcome [4] 0 0
Duration of respiratory support - 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] 0 0
During first hospitalisation (average assessment period 14 weeks)
Secondary outcome [5] 0 0
Bronchopulmonary dysplasia - Bronchopulmonary dysplasia (BPD) will be assessed both clinically (need for mechanical respiratory support and/or an oxygen requirement at 36 weeks corrected gestation), and by a physiological definition. 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 [5] 0 0
36 weeks post menstrual age
Secondary outcome [6] 0 0
Duration of bradycardia and hypoxaemia during intervention - Heart rate and oxygen saturation will be monitored continuously during the intervention. The severity and duration of bradycardia and hypoxia will thus be documented during delivery of exogenous surfactant via brief tracheal catheterisation.
Timepoint [6] 0 0
During intervention
Secondary outcome [7] 0 0
Discomfort during intervention - The incidence of apparent discomfort, as judged by the nurse assisting in the surfactant delivery procedure, will be ascertained in the group randomised to receive surfactant via brief tracheal catheterisation.
Timepoint [7] 0 0
During intervention

Eligibility
Key inclusion criteria
- Gestational age 25-28 completed weeks

- Requiring CPAP or non-invasive positive pressure ventilation with signs of early
respiratory distress.

- CPAP pressure of 5-8 cm H2O and FiO2 >=0.30.

- Less than 6 hours of age.

- Agreement of the Treating Physician in charge of the infant's care.

- Signed parental consent.
Minimum age
No limit
Maximum age
6 Hours
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Previously intubated, or in imminent need of intubation

- Congenital anomaly or condition that might adversely affect breathing.

- Identifiable alternative cause for respiratory distress (e.g. congenital pneumonia or
pulmonary hypoplasia).

- Lack of availability of an OPTIMIST treatment team.

Study design
Purpose of the study
Supportive Care
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
TAS,VIC
Recruitment hospital [1] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [2] 0 0
Royal Womens Hospital - Melbourne
Recruitment hospital [3] 0 0
Mercy Hospital for Women - Melbourne
Recruitment hospital [4] 0 0
Monash Medical Centre - Melbourne
Recruitment postcode(s) [1] 0 0
7000 - Hobart
Recruitment postcode(s) [2] 0 0
3052 - Melbourne
Recruitment postcode(s) [3] 0 0
3084 - Melbourne
Recruitment postcode(s) [4] 0 0
3168 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Connecticut
Country [2] 0 0
United States of America
State/province [2] 0 0
Hawaii
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
New Jersey
Country [5] 0 0
United States of America
State/province [5] 0 0
West Virginia
Country [6] 0 0
Israel
State/province [6] 0 0
Haifa
Country [7] 0 0
Israel
State/province [7] 0 0
Tsefat
Country [8] 0 0
New Zealand
State/province [8] 0 0
Auckland
Country [9] 0 0
Slovenia
State/province [9] 0 0
Ljubljana
Country [10] 0 0
Turkey
State/province [10] 0 0
Bursa
Country [11] 0 0
Turkey
State/province [11] 0 0
Ankara

Funding & Sponsors
Primary sponsor type
Other
Name
Menzies Institute for Medical Research
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Royal Hobart Hospital
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Royal Women's Hospital, Melbourne, Australia
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
NorthShore University HealthSystem
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Monash Medical Centre
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Mercy Hospital for Women, Australia
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Auckland City Hospital
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
Middlemore Hospital, New Zealand
Address [7] 0 0
Country [7] 0 0
Other collaborator category [8] 0 0
Other
Name [8] 0 0
Zekai Tahir Burak Women's Health Research and Education Hospital
Address [8] 0 0
Country [8] 0 0
Other collaborator category [9] 0 0
Other
Name [9] 0 0
Kapiolani Medical Center For Women & Children
Address [9] 0 0
Country [9] 0 0
Other collaborator category [10] 0 0
Other
Name [10] 0 0
The Cooper Health System
Address [10] 0 0
Country [10] 0 0
Other collaborator category [11] 0 0
Other
Name [11] 0 0
Yale University
Address [11] 0 0
Country [11] 0 0
Other collaborator category [12] 0 0
Other
Name [12] 0 0
West Virginia University Hospital
Address [12] 0 0
Country [12] 0 0
Other collaborator category [13] 0 0
Other
Name [13] 0 0
Uludag University Hospital
Address [13] 0 0
Country [13] 0 0
Other collaborator category [14] 0 0
Other
Name [14] 0 0
Ziv Medical Center
Address [14] 0 0
Country [14] 0 0
Other collaborator category [15] 0 0
Other
Name [15] 0 0
Bnai Zion Medical Center
Address [15] 0 0
Country [15] 0 0
Other collaborator category [16] 0 0
Other
Name [16] 0 0
University Medical Centre Ljubljana
Address [16] 0 0
Country [16] 0 0
Other collaborator category [17] 0 0
Other
Name [17] 0 0
Dunedin Hospital
Address [17] 0 0
Country [17] 0 0
Other collaborator category [18] 0 0
Other
Name [18] 0 0
Kanuni Sultan Suleyman Training and Research Hospital
Address [18] 0 0
Country [18] 0 0
Other collaborator category [19] 0 0
Other
Name [19] 0 0
University Medical Center Groningen
Address [19] 0 0
Country [19] 0 0
Other collaborator category [20] 0 0
Other
Name [20] 0 0
University of Southern California
Address [20] 0 0
Country [20] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial question: 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)? Trial hypothesis: That early surfactant administration via a
minimally-invasive technique to preterm infants on CPAP will result in a lesser duration of
mechanical respiratory support, and a higher incidence of survival without bronchopulmonary
dysplasia. Trial design: Multicentre, randomised, masked, controlled trial 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 receive 200 mg/kg of poractant alfa (Curosurf) administered under direct
laryngoscopy using a surfactant instillation catheter, followed by reinstitution of CPAP.
Controls continue on CPAP. The intervention is masked from the clinical team. Care thereafter
is as per usual in both groups, other than the requirement to adhere to intubation criteria.
The primary outcome is incidence of death or BPD. Secondary outcomes 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 is 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 5 years in multiple centres internationally.
Trial website
https://clinicaltrials.gov/show/NCT02140580
Trial related presentations / publications
Dargaville PA, Aiyappan A, De Paoli AG, Kuschel CA, Kamlin CO, Carlin JB, Davis PG. Minimally-invasive surfactant therapy in preterm infants on continuous positive airway pressure. Arch Dis Child Fetal Neonatal Ed. 2013 Mar;98(2):F122-6. doi: 10.1136/archdischild-2011-301314. Epub 2012 Jun 9.
Dargaville PA, Aiyappan A, Cornelius A, Williams C, De Paoli AG. Preliminary evaluation of a new technique of minimally invasive surfactant therapy. Arch Dis Child Fetal Neonatal Ed. 2011 Jul;96(4):F243-8. doi: 10.1136/adc.2010.192518. Epub 2010 Oct 21.
Dargaville PA. Innovation in surfactant therapy I: surfactant lavage and surfactant administration by fluid bolus using minimally invasive techniques. Neonatology. 2012;101(4):326-36. doi: 10.1159/000337346. Epub 2012 Jun 1. Review.
Public notes

Contacts
Principal investigator
Name 0 0
Peter A Dargaville, MD
Address 0 0
Menzies Institute of Medical Research, University of Tasmania
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications