OPTIMIST-A Trial: Minimally-invasive Surfactant Therapy in Preterm Infants 25-28 Weeks Gestation on CPAP

NCT02140580 | Unknown Phase 4 DMC

• 1 other identifier: 4.3, 6th June 2013
• Study Type: interventional
• Target: 486
• Locations: 6 countries
• Sites: 16

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.

Conditions

Bronchopulmonary Dysplasia

Keywords

Minimally-invasive surfactant therapy

Outcome Measures

Primary Outcomes (1)

• 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.

  36 weeks post menstrual age

Secondary Outcomes (7)

• Mortality

  36 weeks post menstrual age

• Major morbidity

  36 weeks post menstrual age

• Pneumothorax

  36 weeks post menstrual age

• Duration of respiratory support

  During first hospitalisation (average assessment period 14 weeks)

• Bronchopulmonary dysplasia

  36 weeks post menstrual age

Other Outcomes (1)

• Hospitalisation cost

  First hospitalisation (average assessment period 14 weeks)

Study Arms (2)

Minimally invasive surfactant therapy

ACTIVE COMPARATOR

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.

Device: Minimally invasive surfactant therapy

Continuation on CPAP

SHAM COMPARATOR

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.

Other: Continuation on CPAP

Interventions

Minimally invasive surfactant therapy DEVICE

Active Comparator

Also known as: 16G Angiocath, Product No. 382259, BD, Sandy, UT, USA

Minimally invasive surfactant therapy

Continuation on CPAP OTHER

Sham Comparator

Also known as: Standard care - continuation of CPAP

Continuation on CPAP

Eligibility Criteria

• Age: 1 Minute - 6 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Menzies Institute for Medical Research: lead
• Royal Hobart Hospital: collaborator
• Royal Women's Hospital, Melbourne, Australia: collaborator
• Endeavor Health: collaborator
• Monash Medical Centre: collaborator
• Mercy Hospital for Women, Australia: collaborator
• Auckland City Hospital: collaborator
• Middlemore Hospital, New Zealand: collaborator
• Zekai Tahir Burak Women's Health Research and Education Hospital: collaborator
• Kapiolani Medical Center For Women & Children: collaborator
• The Cooper Health System: collaborator
• Yale University: collaborator
• Uludag University: collaborator
• Ziv Medical Center: collaborator
• Bnai Zion Medical Center: collaborator
• University Medical Centre Ljubljana: collaborator
• Dunedin Hospital: collaborator
• University Medical Center Groningen: collaborator
• University of Southern California: collaborator
• West Virginia University Hospital: collaborator
• Kanuni Sultan Suleyman Training and Research Hospital: collaborator

Study Sites (16)

Yale-New Haven Children's Hospital

New Haven, Connecticut, 06520-8081, United States

Location

Kapi'olani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States

Location

NorthShore Health University HealthSystem Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

West Virginia University Hospital

Morgantown, West Virginia, 26506, United States

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Royal Womens Hospital

Melbourne, Victoria, 3052, Australia

Location

Mercy Hospital for Women

Melbourne, Victoria, 3084, Australia

Location

Monash Medical Centre

Melbourne, Victoria, 3168, Australia

Location

Bnai Zion Medical Center

Haifa, 31048, Israel

Location

Ziv Medical Center

Safed, 13100, Israel

Location

Auckland City Hospital

Auckland, 1142, New Zealand

Location

Middlemore Hospital

Auckland, 1640, New Zealand

Location

University Medical Center, Ljubljana

Zaloska, Ljubljana, SI-1525, Slovenia

Location

Uludag University Hospital

Görükle, Bursa, 16120, Turkey (Türkiye)

Location

Zekai Tahir Burak Hospital

Ankara, 06230, Turkey (Türkiye)

Location

Related Publications (5)

• 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.

  PMID: 22684154 BACKGROUND

• 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.

  PMID: 20971722 BACKGROUND

• 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.

  PMID: 22940622 BACKGROUND

• Dargaville PA. CPAP, Surfactant, or Both for the Preterm Infant: Resolving the Dilemma. JAMA Pediatr. 2015 Aug;169(8):715-7. doi: 10.1001/jamapediatrics.2015.0909. No abstract available.

  PMID: 26053233 DERIVED

• Dargaville PA, Kamlin CO, De Paoli AG, Carlin JB, Orsini F, Soll RF, Davis PG. The OPTIMIST-A trial: evaluation of minimally-invasive surfactant therapy in preterm infants 25-28 weeks gestation. BMC Pediatr. 2014 Aug 27;14:213. doi: 10.1186/1471-2431-14-213.

  PMID: 25164872 DERIVED

MeSH Terms

Conditions

Bronchopulmonary Dysplasia

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Peter A Dargaville, MD

  Menzies Institute of Medical Research, University of Tasmania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Neonatologist, Paediatric and Neonatal Intensive Care Unit, Royal Hobart Hospital

Study Record Dates

• First Submitted: May 13, 2014
• First Posted: May 16, 2014
• Study Start: December 1, 2011
• Primary Completion: May 1, 2020
• Study Completion: June 1, 2022
• Last Updated: May 1, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (2); IL (2); TU (2); SL (1); AU (4); US (5)