Clinical trial NCT01037634: Safety and Efficacy of Oseltamivir in Children Younger Than One Year of Age
Official title: Oseltamivir Treatment in Children Under One Year of Age With Moderate or Severe Influenza Lower Respiratory Tract Infection - a Clinical and Pharmacokinetic Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Influenza
Keywords: Avian Influenza
H1N1 Influenza
Seasonal Influenza
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2009-12-23
Enrollment: 0
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Currently, there is no standard treatment for influenza with related lower respiratory tract infection (LRTI) in children younger than one year of age, even though influenza related LRTI is a potentially fatal illness in these children. This study will test a medicine for influenza in children younger than one year of age to see if it is safe and effective.

Detailed description: Influenza-related lower respiratory tract infection (LRTI) can cause serious illness or death in children younger than a year old. Only four medications are registered to treat influenza, and these do not have detailed recommendations for treating children younger than one year of age. One of these medications, oseltamivir, has no official recommendation for usage in children younger than one year of age, but it may be the best treatment for certain strains of influenza. A small number of children younger than one year of age have received oseltamivir in several countries with good clinical outcomes and apparently good tolerability. This study will test oseltamivir in children younger than one year of age to see if it is safe and effective.

Children younger than one year of age with influenza will be recruited for this study. Participants will receive the usual care for influenza with the addition of oseltamivir. Oseltamivir will be given orally for 5 days to children with human influenza, 7 days to children with H1N1 influenza in Vietnam, and 10 days to children with avian influenza. Participants will need to remain in the hospital between 5 and 12 days, depending on their illnesses.

Study assessments will be performed daily for 14 days with follow-up examinations occurring 1 to 2 weeks, 6 months, and 12 months after study entry. These assessments will include normal tests for children with influenza, such as blood tests and chest x-rays, but additional blood and nose, throat, and mouth samples will be collected for the study. Participants on a breathing machine will give lung samples.

Eligibility criteria: Inclusion Criteria:

* Informed consent signed by a parent or legal guardian
* Younger than 12 months of age when first seen with a lower respiratory tract infection (LRTI)
* LRTI must be moderate or severe and influenza must be virologically proven by a respiratory specimen
* History of fever within 14 days prior to presentation (although fever at presentation is not required) plus any two of the following: cough, difficulty breathing or shortness of breath, increased respiratory rate for current age, intercostal recession, use of accessory muscles, nasal flare or grunting, crepitations with or without wheezing, a consistent abnormal chest x-ray (e.g., new infiltrate, hyperinflation)
* Virological evidence of influenza on any one of the tests specified in the protocol

Exclusion Criteria for Children with Non-Avian Influenza:

* Known allergy to oseltamivir

Additional Exclusion Criteria for Children with Non-Avian Influenza:

* Illness duration greater than 14 days on the day of hospital admission
* Creatinine clearance less than 10 mL/min/1.73m2, including a requirement for dialysis or hemofiltration

Primary outcomes:
measure: Viral clearance of human influenza on a nose and throat swab, assessed by reverse transcriptase polymerase chain reaction (RT PCR)
timeFrame: Measured on Day 5
measure: Viral clearance of H1N1 swine influenza, version found in Vietnam only, on a nose and throat swab, assessed by RT PCR
timeFrame: Measured on Day 7
measure: Viral clearance of avian influenza on a nose and throat swab, assessed by RT PCR
timeFrame: Measured on Day 10
Secondary outcomes:
measure: Time to viral clearance on a throat and nose swab, assessed by RT PCR
timeFrame: Measured over 14 days
measure: The time to no detectable influenza virus by culture for the throat and nose swabs
timeFrame: Measured over 14 days
measure: Change in viral load (by log10 copies/mL) over time for all virological samples, with a lower limit of detection of 1,000 copies/mL
timeFrame: Measured over 14 days
measure: Viral susceptibility of cultured influenza virus to antiviral drugs, assessed by genotypical and phenotypical analyses
timeFrame: Measured at baseline and post-treatment
measure: Time to fever clearance
timeFrame: Measured over 14 days
measure: In-hospital mortality and mortality by follow-up
timeFrame: Measured over one year
measure: Time to death
timeFrame: Measured at study completion
measure: Time to trans-cutaneous O2 saturation of greater than or equal to 95% on room air
timeFrame: Measured at study completion
measure: Clinical course: pneumothorax, encephalitis/encephalopathy
timeFrame: Measured at study completion
measure: Number of days in hospital
timeFrame: Measured at study completion
measure: Number of days ventilated
timeFrame: Measured at study completion
measure: Documented serious adverse events (SAEs) and relationships to oseltamivir
timeFrame: Measured at study completion
measure: Adverse events (AEs) leading to drug withdrawal
timeFrame: Measured at study completion
measure: Grade 3 and 4 clinical and laboratory AEs that are probably or definitely related to oseltamivir
timeFrame: Measured at study completion
measure: Skin rashes of any grade
timeFrame: Measured at study completion
measure: Changes in hematological and biochemical parameters over time
timeFrame: Measured at study completion
measure: Pharmacokinetic endpoints, including maximum concentration (Cmax), time of Cmax (Tmax), steady state minimum concentration (Cmin), area under the curve (AUC), and volume of distribution
timeFrame: Measured at baseline, Days 1 to 4, Day 7, and Day 9
Other outcomes:
Locations:
Study officials:
affiliation: Mahidol Oxford University Research
name: Bob Taylor, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Broor S, Parveen S, Bharaj P, Prasad VS, Srinivasulu KN, Sumanth KM, Kapoor SK, Fowler K, Sullender WM. A prospective three-year cohort study of the epidemiology and virology of acute respiratory infections of children in rural India. PLoS One. 2007 Jun 6;2(6):e491. doi: 10.1371/journal.pone.0000491.
citation: American Academy of Pediatrics Committee on Infectious Diseases. Antiviral therapy and prophylaxis for influenza in children. Pediatrics. 2007 Apr;119(4):852-60. doi: 10.1542/peds.2007-0224.
citation: Ferraris O, Lina B. Mutations of neuraminidase implicated in neuraminidase inhibitors resistance. J Clin Virol. 2008 Jan;41(1):13-9. doi: 10.1016/j.jcv.2007.10.020. Epub 2007 Dec 11.