Clinical trial NCT02442427: "Palivizumab Therapy for RSV-bronchiolitis"
Official title: Treatment of Respiratory Syncytial Virus Bronchiolitis in Young Infants With Humanized Monoclonal Antibody: A Randomized Clinical Trial (Palivizumab Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Respiratory Syncytial Virus-bronchiolitis
Keywords: Respiratory syncytial virus
Palivizumab
Bronchiolitis
Treatment
Lead sponsor: Hamad Medical Corporation
Sponsor class: INDUSTRY
First posted: 2015-05-13
Enrollment: 420
Sex: ALL
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: There is a growing body of literature suggesting that monoclonal antibody could be efficacious in infants with RSV-bronchiolitis, well tolerated with no or clinically insignificant adverse effects.

"The investigators hypothesize that a single dose of iv palivizumab 15 mg/kg in diagnosed infants \<3 months old with RSV bronchiolitis will result in fewer infants with readmissions to infirmary/observation or hospital for relapse during 3 weeks of follow-up after discharge".

Detailed description: Setting:

The study will be conducted between September 2014 and April 2018 in the short stay unit of the Pediatric Emergency Center (PEC) of Hamad General Hospital, the only pediatric emergency facility in the State of Qatar. The PEC serves an average of 280 000 patients annually and manages 42 beds in a short stay infirmary unit, to which patients are admitted if they are too ill to be sent home but do not need the intensive care unit. Patients admitted to the unit are assessed at least every 6 hours by a pediatrician to determine readiness for discharge. The length of stay in the unit for bronchiolitis ranges from 6 to 168 hours. In 2012, the investigators saw 8718 infants and young children in 10 666 visits for bronchiolitis. Infants aged ≤3 months presenting to the unit for treatment of viral bronchiolitis will be eligible for the study. Consecutive patients will be recruited except when a study nurse is unavailable or the unit is too busy to recruit.

Procedure:

Patients will be examined on presentation, and those needing additional treatment or observation will be admitted to the short stay infirmary unit. Consecutive patients with bronchiolitis will be assessed for study eligibility within 2 hours. Eligible patients will be enrolled after obtaining written consent. For those who consent, plain chest radiography, and nasopharyngeal swabs will be taken for RSV detection. If the patient has a positive RSV rapid antigen test, patients will be randomized to receive one of the study arms. Bronchiolitis severity score will be measured initially at the start of treatment and then at 12-hour, 24-hour, 36-hour and 48-hour thereafter. The medical team in addition to the parents and patients will be blinded to the medication delivered. Adverse effects in each group will be carefully monitored and documented. Patients will be sent home with salbutamol metered-dose inhalers with an appropriately sized Aerochamber with mask attachment. Daily follow-up by study nurse by telephone is mandatory for 1 week after discharge and then once a week for 2 weeks thereafter. The patient could return to the pediatric emergency center earlier if needed. At all revisits for the same illness, nasopharyngeal swabs will be taken for RSV rapid antigen test and the result recorded.

Study Intervention:

* Active arm: A single dose of IV palivizumab 15 mg per kilogram body weight (maximum dose =100 mg).
* Control arm: Placebo (an equivalent volume of 0.9% normal saline).

Eligibility criteria: Inclusion Criteria:

* Infants ≤ 3 months-old, presenting to the main pediatric ER with acute bronchiolitis associated with positive RSV rapid antigen test.

Exclusion Criteria:

* Patients will be excluded from the study if they had 1 or more of the following characteristics:

  * Received monoclonal antibody or IVIG within the last 3 months prior to randomization.
  * Receipt of steroids within 2 days before randomization.
  * Hypersensitivity to monoclonal antibodies or immunoglobulin products.
  * Immunodeficiency.
  * Suspected sepsis.
  * Seizure disorders.
  * Neuromuscular disorders.
  * Congenital heart disease.
  * Major congenital anomalies of respiratory tract.

Primary outcomes:
measure: Readmission to either infirmary/observation or hospital or PICU during 3 weeks of follow-up after discharge
timeFrame: 3 weeks
Secondary outcomes:
measure: Time to medical readiness for discharge
timeFrame: 4 weeks
measure: Revisit to any medical facility for the same illness
timeFrame: 4 weeks
measure: Admission to PICU during initial admission
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Doha
country: Qatar
facility: Hamad Medical Corporation
Study officials:
affiliation: Hamad Medical Corporation, Doha, Qatar
name: Dr. Khalid Alansari
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alansari K, Toaimah FH, Almatar DH, El Tatawy LA, Davidson BL, Qusad MIM. Monoclonal Antibody Treatment of RSV Bronchiolitis in Young Infants: A Randomized Trial. Pediatrics. 2019 Mar;143(3):e20182308. doi: 10.1542/peds.2018-2308. Epub 2019 Feb 13.