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

Bronchiolitis, Viral Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03959384
• Other study ID #: SURFABRON
• Status: Terminated
• Phase: Phase 3
• Start date: January 9, 2019
• Est. completion date: April 9, 2021

Study information

• Verified date: April 2021
• Source: Azienda Ospedaliera Universitaria Integrata Verona
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: April 9, 2021
• Est. primary completion date: April 9, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Weeks to 12 Months

Eligibility

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

Related Conditions & MeSH terms

• Bronchiolitis
• Bronchiolitis, Viral

Intervention

Drug:
• Curosurf 80Mg/Ml Intratracheal Suspension
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.

Other:
• Ambient Air
Ambient air aspirated in sterile syringes

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera Universitaria Integrata Verona	Verona

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliera Universitaria Integrata Verona

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of days free from non-invasive mechanical ventilation in the post-extubation phase	Number of days free from non-invasive mechanical ventilation in the post-extubation phase	day 14
Secondary	Number of cases requiring new intubation	Number of cases requiring new intubation after previous extubation in 14 days from randomization.	day 14
Secondary	Number of days of patients in PICU	Number of days of patients in PICU	day 14
Secondary	Number of days of hospitalization	Number of days of hospitalization.	day 14
Secondary	Number of days free from oxygen supplementation	Number of days free from oxygen supplementation	day 14
Secondary	Values of the Oxygen Saturation Index (OSI)	Changes in the Oxygen Saturation Index (OSI)	detected 15 minutes before administration of treatment and at a distance of 2, 6, 12, 24, 36 and 48 hours
Secondary	Values of the mechanical ventilation parameter (MAP) during invasive mechanical respiratory support	Changes in the ventilatory parameter (MAP) during invasive mechanical respiratory support	detected 15 minutes before administration of treatment and at a distance of 2, 6, 12, 24, 36 and 48 hours
Secondary	Number of patients undergoing a repeated treatment (Curosurf or placebo)	Number of patients undergoing a repeated treatment (Curosurf or placebo). The repetition of the assigned treatment may take place at least 12 hours apart and in any case within 24 hours of the first treatment, at the same dosage and with the same method of administration	within 24 hours of the first treatment
Secondary	Number of patients undergoing unconventional or more invasive treatments (HFOV, Nitric Oxide, ECMO)	Number of patients undergoing unconventional or more invasive treatments (HFOV, Nitric Oxide, ECMO)	during the first 14 days
Secondary	Rate of deaths	Rate of deaths before hospital discharge	(1) Mortality during the first 14 days of hospitalization (2) Mortality from the date of the first intervention until the date of hospital discharge
Secondary	Number of serious desaturation episodes, severe bradycardia, extreme bradycardia or cardiac arrest, pulmonary hemorrhage, pneumothorax	Number of serious desaturation episodes (SatO2 < 75%), episodes of severe bradycardia (FC < 80/min) , episodes of extreme bradycardia or cardiac arrest with the need for chest compressions and/or administration of drugs for resuscitation, episodes of pulmonary hemorrhage, episodes of pneumothorax	within the first 48 hours after treatment