Condition category
Neonatal Diseases
Date applied
03/09/2019
Date assigned
06/09/2019
Last edited
06/09/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Hypoxemic respiratory failure (HRF) is a leading cause of illness and death among term and near term newborns. Few studies have tested surfactant treatment in these patients with conflicting results. The aim of this study is to test whether early use of surfactant in combination with inhaled nitric oxide (iNO) will prevent newborns with moderate hypoxemic respiratory failure from developing severe HRF.

Who can participate?
Term and near-term newborns (35 weeks gestational ages and over) with acute HRF

What does the study involve?
Participants are randomly allocated to one of two groups. The surfactant-iNO group receive the combined treatment of surfactant plus inhaled Nitric Oxide (iNO). The control group receive standard treatment with iNO. Infants of both groups receive standard intensive care, which includes high frequency or conventional mechanical ventilation, inotropic support and sedation. ECMO was considered in patients with a persistent OI>40.

What are the possible benefits and risks of participating?
It is expected that the combined treatment of inhaled Nitric Oxide and surfactant will help to improve oxygenation and prevent the progression to severe HRF. This may reduce mortality and the need for ECMO treatment. Surfactant is a usual therapy for preterms with respiratory distress, occasionally its administration is associated with oxygen desaturation and bleeding, but the incidence of these complications is minimized with careful application and monitoring.

Where is the study run from?
Five level III Neonatal Intensive Care Units in five hospitals in Chile

When is the study starting and how long is it expected to run for?
August 2008 to July 2015

Who is funding the study?
Chilean National Fund for Research in Health (FONIS)

Who is the main contact?
Dr Alvaro González
alvgonza@med.puc.cl

Trial website

Contact information

Type

Scientific

Primary contact

Dr Alvaro González

ORCID ID

http://orcid.org/0000-0002-0442-9109

Contact details

Diagonal Paraguay 362
8° piso
Santiago
8330077
Chile
+56 (0)223543887
alvgonza@med.puc.cl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

FONIS SA07I20035

Study information

Scientific title

Randomized controlled trial to assess the early addition of exogenous surfactant to inhaled nitric oxide in the treatment of newborns with respiratory failure and pulmonary hypertension

Acronym

Surfactant plus Nitric Oxide in Neonatal Hypoxic Respiratory Failure

Study hypothesis

The early addition of exogenous surfactant to the treatment with inhaled Nitric Oxide of newborns with respiratory failure (OI>20) and pulmonary hypertension will improve oxygenation and prevent them from developing severe hypoxemic respiratory failure (OI > 40).

Ethics approval

Approved 08/07/2007, Research Ethics Committee of Medicine School Pontificia Universidad Catolica de Chile (Comité Etico Científico Facultad de Medicina, Pontificia Universidad Católica de Chile, Diagonal Paraguay 383, Torre 11, Local 4, Santiago, Chile 8330077; Tel: +56 (0)2 23548173; Email: cecmeduc@med.puc.cl), CE# 027807

Study design

Prospective randomized double-blind placebo-controlled clinical trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contacat details to request a participant information sheet

Condition

Neonatal hypoxic respiratory failure and pulmonary hypertension

Intervention

Enrolled infants were randomized into one of the two study groups using sequential sealed opaque envelopes from a computer-generated randomization list. This allocation sequence was generated centrally by an independent statistician, and sequentially sealed envelopes were sent to each center.

Surfactant-iNO group: received treatment with 20 ppm of inhaled Nitric Oxide (INOmax, INO Therapeutics, USA) with up to 2 doses of 100 mg/kg of poractant alfa (Curocerf; Chiesi Farmaceutici, Italy)

Control group: received treatment with 20 ppm iNO + placebo (air) and standard intensive care, which in both groups includes high frequency or conventional mechanical ventilation with 100% FiO2., inotropic support and sedation

Infants in both groups could receive open-label surfactant if they developed an OI>40 within the first 48 hrs of study. ECMO was considered in patients with a persistent OI>40.

Study surfactant combined with iNitric Oxide treatment were used within first 48 hours after study entry, but infants continue receiving standard intensive care later according to local and physician in charge guidelines. Patients were strictly monitored and followed during their whole hospital stay until discharge home.

Intervention type

Mixed

Phase

Drug names

Primary outcome measure

The proportion of infants developing treatment failure during the first 48 hours of study treatment, defined as an oxygenation index (OI) ≥ 40

Secondary outcome measures

1. Proportion of infants requiring ECMO or death recorded during hospital stay
2. Oxygen and ventilatory requirements recorded during hospital stay

Overall trial start date

01/08/2008

Overall trial end date

31/07/2015

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Near term infants (35 weeks gestation) with birth weights > 2000 g and who are less than 72 hours old
2. Infants requiring mechanical ventilation with hypoxemic respiratory failure with an OI > 20, calculated on two consecutive measurements of post ductal arterial blood gases without acidosis (pH > 7.25) and efforts will be done to adjust ventilatory support to reach a PCO2 < 60
3. A previous echocardiogram will be performed to rule out a cardiac anomaly and evaluate the presence of pulmonary hypertension (a tricuspid insufficiency jet with an estimated systolic pulmonary artery pressure ≥ 2/3 of systemic systolic arterial blood pressure and/or evidence of right-to-left shunting through foramen ovale or ductus arteriosus)

Participant type

Patient

Age group

Neonate

Gender

Both

Target number of participants

100

Participant exclusion criteria

1. Life-threatening congenital anomalies
2. Congenital heart disease
3. Congenital diaphragmatic hernia
4. Other forms of lung hypoplasia syndromes
5. Suspected or confirmed chromosomal abnormality
6. Postnatal age > 72 hours

Recruitment start date

01/03/2009

Recruitment end date

30/04/2014

Locations

Countries of recruitment

Chile

Trial participating centre

Hospital Clinico Pontificia Universidad Catolica de Chile
Marcoleta 367
Santiago
8330077
Chile

Trial participating centre

Hospital Regional Guillermo Grant Benavente, Concepción
San Martin 1436
Concepción
4070038
Chile

Trial participating centre

Hospital Dr Luis Tisné
Avenida Las Torres 5150
Santiago
8640002
Chile

Trial participating centre

Hosptal Dr Sóteo del Río
Avenida Concha y Toro 3459 Puente Alto
Santiago
8207257
Chile

Trial participating centre

Hospital San José
San José 1196 Independencia
Santiago
8380419
Chile

Sponsor information

Organisation

Pontificia Universidad Católica de Chile

Sponsor details

Department of Neonatology
School of Medicine
Diagonal Paraguay 362
8° piso
Santiago
8330077
Chile
+56 (0)23543887
jfabres@med.puc.cl

Sponsor type

University/education

Website

https://medicina.uc.cl

Funders

Funder type

Government

Funder name

Chilean Fund for Health Research (FONIS): SA07I20035

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Results were presented in part at Pediatric Academic Societies meetings in Chile and internationally, and will be published at Pediatric Journal.

IPD sharing statement
Deidentified individual participant data will be made available, in addition to study protocols, the statistical analysis plan, and the informed consent form. The data will be made available upon publication to researchers who provide a methodologically sound proposal for use in achieving the goals of the approved proposal. Proposals should be submitted to alvgonza@med.puc.cl

Intention to publish date

15/11/2019

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

06/09/2019: Trial's existence confirmed by institutional review board and funder.