Clinical trial NCT03959384: Efficacy and Safety of Curosurf® in Patients Invasively Ventilated for Severe Bronchiolitis Under 12 Months of Age
Official title: Efficacy and Safety of Curosurf® in Patients Under 12 Months of Age Requiring Invasive Mechanical Ventilation for Acute Respiratory Distress Syndrome in the Course of Bronchiolitis: A Randomized, Double-blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Bronchiolitis, Viral
Lead sponsor: Azienda Ospedaliera Universitaria Integrata Verona
Sponsor class: OTHER
First posted: 2019-05-22
Enrollment: 9
Sex: ALL
Minimum age (years): 40
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: multicenter, double-blind, placebo-controlled, randomized trial
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. 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.
2. Recent phase of oxygen dependency (need for oxygen supplementation to maintain satO2 \> 94% in the four weeks preceding hospitalization in Pediatric ICU)
3. Invasive mechanical ventilation for more than 24 hours.
4. Oxygenation index (OI) \> 30
5. Cyanotic congenital heart disease
6. Untreated pneumothorax
7. Neuromuscular diseases
8. Severe Neurological Alterations
9. Other severe congenital anomalies
10. Indication not to attempt resuscitation
11. Patient already recruited for other clinical studies

Primary outcomes:
measure: Number of days free from invasive mechanical ventilation
timeFrame: day 14
Secondary outcomes:
measure: Number of days free from non-invasive mechanical ventilation in the post-extubation phase
timeFrame: day 14
measure: Number of cases requiring new intubation
timeFrame: day 14
measure: Number of days of patients in PICU
timeFrame: day 14
measure: Number of days of hospitalization
timeFrame: day 14
measure: Number of days free from oxygen supplementation
timeFrame: day 14
measure: Values of the Oxygen Saturation Index (OSI)
timeFrame: detected 15 minutes before administration of treatment and at a distance of 2, 6, 12, 24, 36 and 48 hours
measure: Values of the mechanical ventilation parameter (MAP) during invasive mechanical respiratory support
timeFrame: detected 15 minutes before administration of treatment and at a distance of 2, 6, 12, 24, 36 and 48 hours
measure: Number of patients undergoing a repeated treatment (Curosurf or placebo)
timeFrame: within 24 hours of the first treatment
measure: Number of patients undergoing unconventional or more invasive treatments (HFOV, Nitric Oxide, ECMO)
timeFrame: during the first 14 days
measure: Rate of deaths
timeFrame: (1) Mortality during the first 14 days of hospitalization (2) Mortality from the date of the first intervention until the date of hospital discharge
measure: Number of serious desaturation episodes, severe bradycardia, extreme bradycardia or cardiac arrest, pulmonary hemorrhage, pneumothorax
timeFrame: within the first 48 hours after treatment
Other outcomes:
Locations:
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona
Study officials:
affiliation: AOUI Verona
name: Paolo Biban, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.