Efficacy and Safety of Curosurf® in Patients Invasively Ventilated for Severe Bronchiolitis Under 12 Months of Age

NCT03959384 | Terminated Phase 3 DMC

• 1 other identifier: SURFABRON
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Background. Viral bronchiolitis is a common cause of hospitalization for acute respiratory insufficiency in young infants. Despite several RCT have tested the effectiveness of various agents, currently there is no proven specific therapy for bronchiolitis, treatment remaining mostly supportive. Based on available studies, exogenous surfactant replacement in bronchiolitis is likely to have a promising safety and efficacy profile. Primary objective. To evaluate whether Curosurf treatment is effective compared to placebo (air) in reducing the duration of invasive mechanical ventilation in the first 14 days of hospitalization, in infants less than 12 months suffering from acute hypoxemic bronchiolitis. Methods. a multicenter, double-blind, placebo-controlled, randomized trial. 19 Italian PICUs will enroll children less than12 months with hypoxemic acute bronchiolitis, with need for invasive mechanical ventilation. Once the patient has been recruited, randomization should occur as quickly as possible. The first dose of Curosurf or placebo should be administered within 60 minutes of randomization. The treatment may be repeated once, not before 12 hours and not later than 24 hours after the initial dose. The assignment of the type of treatment will be communicated by the Coordinator center to the researcher attending the patient's bed. The same medical researcher will then take care of administering the assigned treatment, masking the procedure with appropriate precautions, for example with screens or closing the patient's room whenever possible. The preparation and administration of treatment, medication or placebo, can be done by a nurse who must not disclose the assigned treatment and will not be involved in the patient's care until the conclusion of the study. Patient evaluation will be carried out by other physicians and/or nurses who will not be aware of the assigned treatment. Regardless the received treatment, all patients will be assisted according to standard practice of the Unit. For the purposes of the study, several parameters will be collected 15 minutes before, and 2, 6, 12, 24, 36, 48 hours after administration of the drug: oxygenation indexes such as OI, OSI, PaO2 and SatO2; Invasive ventilation parameters, i.e. current volume, positive end expiratory pressure, peak pressure, respiratory rate, FiO2 and mean airway pressure; and ventilation indexes such as PaCO2 and End Tidal CO2. If it is necessary to repeat the treatment, the above parameters will be re-collected with the same timepoints. During the study all the AE/ADR will be recorded.

Conditions

Bronchiolitis, Viral

Outcome Measures

Primary Outcomes (1)

• Number of days free from invasive mechanical ventilation

  Number of days free from invasive mechanical ventilation within the first 14 days of hospitalization. Ventilation-free days will start after the first successful extubation (at least 48 hours without the need for re-intubation)

  day 14

Secondary Outcomes (11)

• Number of days free from non-invasive mechanical ventilation in the post-extubation phase

  day 14

• Number of cases requiring new intubation

  day 14

• Number of days of patients in PICU

  day 14

• Number of days of hospitalization

  day 14

• Number of days free from oxygen supplementation

  day 14

Study Arms (2)

Surfactant replacement (Curosurf)

EXPERIMENTAL

1. Broncho-alveolar lavage (BAL) with 25 mg / kg of Curosurf, diluted 1:10 with physiological solution, divided in two aliquots administered with a endotracheal tube in two different postures (1st BAL on right decubitus, 2nd BAL on left decubitus). 2. Following supplementation of a dose of 25 mg / kg of Curosurf, diluted with physiological solution 1: 2 (1 ml = 40 mg of surfactant), given in two aliquots with endotracheal tube in two different postures (1st on right decubitus, 2nd on left decubitus). The treatment assigned may be repeated at least 12 hours later and in any case within 24 hours from the first treatment, at the same dosage and with the same method of administration

Drug: Curosurf 80Mg/Ml Intratracheal Suspension

Ambient Air

PLACEBO COMPARATOR

1. Broncho-alveolar lavage (BAL) with air, administered with a endotracheal tube in two different postures (1st BAL on right decubitus, 2nd BAL on left decubitus). 2. Following supplementation of air given with endotracheal tube in two different postures (1st on right decubitus, 2nd on left decubitus). The treatment assigned may be repeated at least 12 hours later and in any case within 24 hours from the first treatment, at the same dosage and with the same method of administration

Other: Ambient Air

Interventions

Curosurf 80Mg/Ml Intratracheal Suspension DRUG

CUROSURF is a natural surfactant obtained from swine lungs containing almost exclusively phospholipids, in particular phosphatidylcholine (about 70% of the total phospholipid content) and about 1% of low molecular weight hydrophobic proteins, specific for surfactant, SP-B and SP -C. CUROSURF will be administered via endotracheopulmunary.

Also known as: phospholipid fraction from porcine lung

Surfactant replacement (Curosurf)

Ambient Air OTHER

Ambient air aspirated in sterile syringes

Ambient Air

Eligibility Criteria

• Age: 40 Weeks - 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Aged \> 40 weeks (correct gestational age) and \< 12 months.
• Patient intubated and mechanically ventilated for at least 6 hours, with expected requirement of ventilatory support of at least 24 hours.
• Clinical picture strongly suggestive for acute bronchiolitis (fever of probable viral origin, fine crackles, prolonged expiration, lung hyperexpansion on chest X-ray)
• Moderate or severe pediatric acute respiratory distress syndrome, defined by a Oxygenation Index (OI) \> 8 or an Oxygen Saturation Index (OSI) \> 7.5
• Written informed consent obtained from both parents

You may not qualify if:

• Severe prematurity (gestational age \< 32 weeks). Patients with gestational age less than 32 weeks will be excluded because they are considered at high risk for respiratory pathology following their severe prematurity. This consideration does not apply in successive gestational ages. Therefore patients with mild prematurity, i.e. with gestational age equal to or greater than 32 weeks, are not to be excluded.
• Recent phase of oxygen dependency (need for oxygen supplementation to maintain satO2 \> 94% in the four weeks preceding hospitalization in Pediatric ICU)
• Invasive mechanical ventilation for more than 24 hours.
• Oxygenation index (OI) \> 30
• Cyanotic congenital heart disease
• Untreated pneumothorax
• Neuromuscular diseases
• Severe Neurological Alterations
• Other severe congenital anomalies
• Indication not to attempt resuscitation
• Patient already recruited for other clinical studies

Sponsors & Collaborators

• Azienda Ospedaliera Universitaria Integrata Verona: lead

Study Sites (1)

Azienda Ospedaliera Universitaria Integrata Verona

Verona, 37126, Italy

Location

Related Publications (1)

• Biban P, Conti G, Wolfler AM, Carlassara S, Gitto E, Rulli I, Moscatelli A, Micalizzi C, Savron F, Sagredini R, Genoni G, Binotti M, Caramelli F, Fae M, Pettenazzo A, Stritoni V, D'Amato L, Zito Marinosci G, Calderini E, Scalia Catenacci S, Berardi A, Torcetta F, Bonanomi E, Bonacina D, Ivani G, Santuz P. Efficacy and safety of exogenous surfactant therapy in patients under 12 months of age invasively ventilated for severe bronchiolitis (SURFABRON): protocol for a multicentre, randomised, double-blind, controlled, non-profit trial. BMJ Open. 2020 Oct 19;10(10):e038780. doi: 10.1136/bmjopen-2020-038780.

  PMID: 33077567 DERIVED

MeSH Terms

Conditions

Bronchiolitis, Viral

Interventions

poractant alfa; Particulate Matter

Condition Hierarchy (Ancestors)

Bronchiolitis; Bronchitis; Respiratory Tract Infections; Infections; Virus Diseases; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Intervention Hierarchy (Ancestors)

Complex Mixtures

Study Officials

• Paolo Biban, MD

  AOUI Verona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Patient's parents and the doctors/nurses responsible for the patient's care will be blinded. At each center only a physician and a nurse will know and prepare the drug or placebo, being subsequently not clinically involved in the care of that particular patient. The assignment of the type of treatment will be communicated by the Coordinator centre in an individual way and reserved to the researcher attending the patient's bed. The same medical researcher will then take care of administering the treatment assigned to the patient, masking the procedure with appropriate precautions. The preparation and administration of treatment can be done with the help of a nurse who does not have to disclose the type of treatment assigned. Thereafter, such a nurse will not be involved in the patient's care until the conclusion of the study. The patient evaluation will be carried out by other physicians and/or nurses who will not be aware of the type of treatment carried out.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Department of Neonatal and Pediatric Critical Care

Model Details: multicenter, double-blind, placebo-controlled, randomized trial

Study Record Dates

• First Submitted: April 9, 2019
• First Posted: May 22, 2019
• Study Start: January 9, 2019
• Primary Completion: April 9, 2021
• Study Completion: April 9, 2021
• Last Updated: April 15, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be available within 9 months of study completion, up to five years
• Access Criteria: Data access request will be reviewed by the Steering committee. Requestors wil be required to sign a Data Access Agreement

Locations

IT (1)