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

Influenza Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01037634
• Other study ID #: SEA 022
• Status: Withdrawn
• Phase: Phase 2
• First received: December 18, 2009
• Last updated: August 5, 2014
• Start date: March 2010

Study information

• Verified date: August 2014
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Month to 12 Months

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Influenza
• Influenza, Human
• Respiratory Tract Infections

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

References & Publications (3)

American Academy of Pediatrics Committee on Infectious Diseases. Antiviral therapy and prophylaxis for influenza in children. Pediatrics. 2007 Apr;119(4):852-60. Review. — View 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. — View Citation

Ferraris O, Lina B. Mutations of neuraminidase implicated in neuraminidase inhibitors resistance. J Clin Virol. 2008 Jan;41(1):13-9. Epub 2007 Dec 11. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Viral clearance of human influenza on a nose and throat swab, assessed by reverse transcriptase polymerase chain reaction (RT PCR)		Measured on Day 5	Yes
Primary	Viral clearance of H1N1 swine influenza, version found in Vietnam only, on a nose and throat swab, assessed by RT PCR		Measured on Day 7	Yes
Primary	Viral clearance of avian influenza on a nose and throat swab, assessed by RT PCR		Measured on Day 10	Yes
Secondary	Time to viral clearance on a throat and nose swab, assessed by RT PCR		Measured over 14 days	Yes
Secondary	The time to no detectable influenza virus by culture for the throat and nose swabs		Measured over 14 days	No
Secondary	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		Measured over 14 days	Yes
Secondary	Viral susceptibility of cultured influenza virus to antiviral drugs, assessed by genotypical and phenotypical analyses		Measured at baseline and post-treatment	No
Secondary	Time to fever clearance		Measured over 14 days	Yes
Secondary	In-hospital mortality and mortality by follow-up		Measured over one year	Yes
Secondary	Time to death		Measured at study completion	Yes
Secondary	Time to trans-cutaneous O2 saturation of greater than or equal to 95% on room air		Measured at study completion	No
Secondary	Clinical course: pneumothorax, encephalitis/encephalopathy		Measured at study completion	No
Secondary	Number of days in hospital		Measured at study completion	Yes
Secondary	Number of days ventilated		Measured at study completion	Yes
Secondary	Documented serious adverse events (SAEs) and relationships to oseltamivir		Measured at study completion	Yes
Secondary	Adverse events (AEs) leading to drug withdrawal		Measured at study completion	Yes
Secondary	Grade 3 and 4 clinical and laboratory AEs that are probably or definitely related to oseltamivir		Measured at study completion	Yes
Secondary	Skin rashes of any grade		Measured at study completion	Yes
Secondary	Changes in hematological and biochemical parameters over time		Measured at study completion	Yes
Secondary	Pharmacokinetic endpoints, including maximum concentration (Cmax), time of Cmax (Tmax), steady state minimum concentration (Cmin), area under the curve (AUC), and volume of distribution		Measured at baseline, Days 1 to 4, Day 7, and Day 9	No