Safety and Efficacy of Oseltamivir in Children Younger Than One Year of Age

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01037634
First received: December 18, 2009
Last updated: August 5, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Influenza
Drug: Oseltamivir
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Viral clearance of human influenza on a nose and throat swab, assessed by reverse transcriptase polymerase chain reaction (RT PCR) [ Time Frame: Measured on Day 5 ] [ Designated as safety issue: Yes ]
  • Viral clearance of H1N1 swine influenza, version found in Vietnam only, on a nose and throat swab, assessed by RT PCR [ Time Frame: Measured on Day 7 ] [ Designated as safety issue: Yes ]
  • Viral clearance of avian influenza on a nose and throat swab, assessed by RT PCR [ Time Frame: Measured on Day 10 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to viral clearance on a throat and nose swab, assessed by RT PCR [ Time Frame: Measured over 14 days ] [ Designated as safety issue: Yes ]
  • The time to no detectable influenza virus by culture for the throat and nose swabs [ Time Frame: Measured over 14 days ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Measured over 14 days ] [ Designated as safety issue: Yes ]
  • Viral susceptibility of cultured influenza virus to antiviral drugs, assessed by genotypical and phenotypical analyses [ Time Frame: Measured at baseline and post-treatment ] [ Designated as safety issue: No ]
  • Time to fever clearance [ Time Frame: Measured over 14 days ] [ Designated as safety issue: Yes ]
  • In-hospital mortality and mortality by follow-up [ Time Frame: Measured over one year ] [ Designated as safety issue: Yes ]
  • Time to death [ Time Frame: Measured at study completion ] [ Designated as safety issue: Yes ]
  • Time to trans-cutaneous O2 saturation of greater than or equal to 95% on room air [ Time Frame: Measured at study completion ] [ Designated as safety issue: No ]
  • Clinical course: pneumothorax, encephalitis/encephalopathy [ Time Frame: Measured at study completion ] [ Designated as safety issue: No ]
  • Number of days in hospital [ Time Frame: Measured at study completion ] [ Designated as safety issue: Yes ]
  • Number of days ventilated [ Time Frame: Measured at study completion ] [ Designated as safety issue: Yes ]
  • Documented serious adverse events (SAEs) and relationships to oseltamivir [ Time Frame: Measured at study completion ] [ Designated as safety issue: Yes ]
  • Adverse events (AEs) leading to drug withdrawal [ Time Frame: Measured at study completion ] [ Designated as safety issue: Yes ]
  • Grade 3 and 4 clinical and laboratory AEs that are probably or definitely related to oseltamivir [ Time Frame: Measured at study completion ] [ Designated as safety issue: Yes ]
  • Skin rashes of any grade [ Time Frame: Measured at study completion ] [ Designated as safety issue: Yes ]
  • Changes in hematological and biochemical parameters over time [ Time Frame: Measured at study completion ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic endpoints, including maximum concentration (Cmax), time of Cmax (Tmax), steady state minimum concentration (Cmin), area under the curve (AUC), and volume of distribution [ Time Frame: Measured at baseline, Days 1 to 4, Day 7, and Day 9 ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: March 2010
Estimated Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oseltamivir
Participants will receive Oseltamivir to treat influenza.
Drug: Oseltamivir
3 mg/kg given orally for 5 days for seasonal influenza, 7 days for 2009 H1N1 influenza (in Vietnam only), or 10 days for avian influenza, for children whose renal function is greater than or equal to 30 mL/min/1.73m2
Other Name: Tamiflu

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

Ages Eligible for Study:   1 Month to 12 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01037634

Sponsors and Collaborators
Investigators
Principal Investigator: Bob Taylor, MD Mahidol Oxford University Research
  More Information

Publications:
Responsible Party: John Tierney, RN, MPM, RCHSPB
ClinicalTrials.gov Identifier: NCT01037634     History of Changes
Other Study ID Numbers: SEA 022
Study First Received: December 18, 2009
Last Updated: August 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Avian Influenza
H1N1 Influenza
Seasonal Influenza

Additional relevant MeSH terms:
Influenza, Human
Respiratory Tract Infections
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Diseases
Infection
Oseltamivir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 16, 2014