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

NCT ID: NCT02140580

Last Updated: 2020-05-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 486 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2022-06-30

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.

Detailed Description

1. OPTIMIST-A TRIAL SUMMARY RESEARCH 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)?

BACKGROUND Nasal CPAP is often very effective in preterm infants as the initial means of respiratory support, but a sub-group of infants, most with features of respiratory distress syndrome, fail on CPAP and require intubation and ventilation in the first 72 hours. When compared to those in whom CPAP is successful, infants failing CPAP have a substantially longer duration of respiratory support, and a higher risk of adverse outcomes. Decreasing the risk of CPAP failure would thus seem advantageous, and may be achievable with minimally invasive surfactant therapy (MIST), in which surfactant is administered to a spontaneously breathing infant who then remains on CPAP. A technique of MIST (the "Hobart method") using a semi-rigid surfactant instillation catheter has been shown to be feasible in preterm infants on CPAP, and appears to have the potential to alter respiratory course and outcome. This method of MIST now requires evaluation in randomised controlled trials.

RESEARCH DESIGN Multicentre, randomised, masked, controlled trial.

RECRUITMENT Entry criteria Inborn preterm infants 25-28 weeks gestation, aged less than 6 hours, who were not intubated at birth but require CPAP or NIPPV because of respiratory distress, with a CPAP pressure of 5-8 cm H2O and FiO2 ≥0.30.

Exclusion criteria Infants will be excluded if in imminent need of intubation, or if there is a congenital anomaly or alternative cause for respiratory distress.

RANDOMISATION With parental consent, eligible infants will be randomly allocated using a web-based randomisation server, with stratification by study centre, to receive exogenous surfactant via the Hobart MIST technique, or to continue on CPAP.

INTERVENTION Infants randomised to surfactant treatment will receive a dose of poractant alfa (Curosurf) administered under direct laryngoscopy using a surfactant instillation catheter, at a dosage of 200 mg/kg. CPAP will thereafter be reinstituted. Controls will continue on CPAP. The intervention will be masked from the clinical team.

POST-INTERVENTION MANAGEMENT Other than the requirement to adhere to intubation criteria in the first week, and in some cases perform a room air trial at 36 weeks corrected gestation, management after intervention will be at the discretion of the clinical team. Titration of CPAP pressure is encouraged, with a permitted maximum of 8 cm H2O. Nasal IPPV (bi-level CPAP) is allowable. Early caffeine therapy is expected.

Criteria for intubation: Enrolled infants on CPAP will be intubated if FiO2 ≥0.45, or if there is unremitting apnoea or persistent acidosis. These criteria apply during the first week of life, and to the first episode of intubation only.

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. The infant-specific link to the questionnaire, and reminders where necessary, will be sent electronically to the parents by research personnel at each Site, thus maintaining confidentiality. No identifying details will be revealed in the completion of the questionnaire.

OUTCOMES Primary outcome: Incidence of composite outcome of death or physiological bronchopulmonary dysplasia (BPD).

Secondary outcomes: 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.

SAMPLE SIZE 606 infants (303 per group), giving 90% power to detect a 33% reduction in death or BPD from the anticipated rate of 38% in the control arm, α = 0.05.

TRIAL PLAN The OPTIMIST trials will commence at RHH Hobart and RWH Melbourne during 2011. All Australasian neonatal units, and selected international centres including those in the Vermont- Oxford Network, will be invited to join the trials. A full complement of participating centres is expected by early 2014. Recruitment will thereafter proceed at full rate until completion, which is estimated to take up to 4 years.

Conditions

Bronchopulmonary Dysplasia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Minimally invasive surfactant therapy

Intervention Type: DEVICE

Active 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.

Group Type: SHAM_COMPARATOR

Continuation on CPAP

Intervention Type: OTHER

Sham Comparator

Interventions

Minimally invasive surfactant therapy

Active Comparator

Intervention Type: DEVICE

Continuation on CPAP

Sham Comparator

Intervention Type: OTHER

Other Intervention Names

16G Angiocath, Product No. 382259, BD, Sandy, UT, USA; Standard care - continuation of CPAP

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 1 Minute
• Maximum Eligible Age: 6 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Royal Hobart Hospital

OTHER_GOV

Sponsor Role: collaborator

Royal Women's Hospital, Melbourne, Australia

UNKNOWN

Sponsor Role: collaborator

Endeavor Health

OTHER

Sponsor Role: collaborator

Monash Medical Centre

OTHER

Sponsor Role: collaborator

Mercy Hospital for Women, Australia

OTHER

Sponsor Role: collaborator

Auckland City Hospital

OTHER_GOV

Sponsor Role: collaborator

Middlemore Hospital, New Zealand

OTHER

Sponsor Role: collaborator

Zekai Tahir Burak Women's Health Research and Education Hospital

OTHER

Sponsor Role: collaborator

Kapiolani Medical Center For Women & Children

OTHER

Sponsor Role: collaborator

The Cooper Health System

OTHER

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: collaborator

West Virginia University Hospital

UNKNOWN

Sponsor Role: collaborator

Uludag University Hospital

UNKNOWN

Sponsor Role: collaborator

Ziv Medical Center

OTHER

Sponsor Role: collaborator

Bnai Zion Medical Center

OTHER_GOV

Sponsor Role: collaborator

University Medical Centre Ljubljana

OTHER

Sponsor Role: collaborator

Dunedin Hospital

OTHER

Sponsor Role: collaborator

Kanuni Sultan Suleyman Training and Research Hospital

OTHER

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: collaborator

University of Southern California

OTHER

Sponsor Role: collaborator

Menzies Institute for Medical Research

OTHER

Sponsor Role: lead

Responsible Party

Professor Peter Dargaville

Consultant Neonatologist, Paediatric and Neonatal Intensive Care Unit, Royal Hobart Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peter A Dargaville, MD

Role: PRINCIPAL_INVESTIGATOR

Menzies Institute of Medical Research, University of Tasmania

Locations

Yale-New Haven Children's Hospital

New Haven, Connecticut, United States

Kapi'olani Medical Center for Women and Children

Honolulu, Hawaii, United States

NorthShore Health University HealthSystem Evanston Hospital

Evanston, Illinois, United States

Cooper University Hospital

Camden, New Jersey, United States

West Virginia University Hospital

Morgantown, West Virginia, United States

Royal Hobart Hospital

Hobart, Tasmania, Australia

Royal Womens Hospital

Melbourne, Victoria, Australia

Mercy Hospital for Women

Melbourne, Victoria, Australia

Monash Medical Centre

Melbourne, Victoria, Australia

Bnai Zion Medical Center

Haifa, , Israel

Ziv Medical Center

Safed, , Israel

Auckland City Hospital

Auckland, , New Zealand

Middlemore Hospital

Auckland, , New Zealand

University Medical Center, Ljubljana

Zaloska, Ljubljana, Slovenia

Uludag University Hospital

Görükle, Bursa, Turkey (Türkiye)

Zekai Tahir Burak Hospital

Ankara, , Turkey (Türkiye)

Countries

United States; Australia; Israel; New Zealand; Slovenia; Turkey (Türkiye)

References

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.

Reference Type: BACKGROUND

PMID: 22684154 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20971722 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22940622 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26053233 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25164872 (View on PubMed)

Other Identifiers

4.3, 6th June 2013

Identifier Type: -

Identifier Source: org_study_id