NCT00298233

Brief Summary

Influenza, also known as the flu, is a contagious respiratory illness caused by influenza viruses. The illness can range in severity, from mild to severe to even death, and it causes an estimated 500,000 to 1,000,000 deaths worldwide each year. In the last several years, there have been increasing numbers of human cases of avian influenza, or bird flu. This trend may pose a threat of a future pandemic--worldwide outbreak of disease--with an avian influenza virus that can easily spread from person to person. Oseltamivir is an antiviral medication that is used to treat people with uncomplicated human influenza, and it may be effective in treating people with either severe human influenza or avian influenza. The purpose of this international study is to compare standard-dose oseltamivir versus high-dose oseltamivir for treating people who are hospitalized with severe human influenza or avian influenza.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
326

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Feb 2006

Typical duration for phase_2

Geographic Reach
3 countries

12 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2006

Completed
28 days until next milestone

First Submitted

Initial submission to the registry

March 1, 2006

Completed
Same day until next milestone

First Posted

Study publicly available on registry

March 1, 2006

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2010

Completed
4.4 years until next milestone

Results Posted

Study results publicly available

May 22, 2014

Completed
Last Updated

June 6, 2014

Status Verified

May 1, 2014

Enrollment Period

3.9 years

First QC Date

March 1, 2006

Results QC Date

January 17, 2014

Last Update Submit

May 26, 2014

Conditions

InfluenzaAvian InfluenzaSevere Influenza

Keywords

Antibody ResponseAntiviral EfficacyBird FluSevere Respiratory DistressViral Replication and Shedding

Outcome Measures

Primary Outcomes (1)

  • Proportion of All Participants Negative for Viral RNA on Day 5

    Proportion of all participants with no detectable viral RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) in a combined nasal and throat swab sample on day 5.

    After 5 days of treatment

Secondary Outcomes (5)

  • Participants Meeting Criteria for Day 5 Clinical Failure

    After 5 days of treatment

  • In-hospital Mortality Rates

    After up to 10 days of treatment

  • Median Time (Days) Receipt of Oxygen

    Throughout study, 14 days

  • Median Time (Days) in ICU

    Throughout study, 14 days

  • Median Time (Days) on Ventilation

    Throughout study, 14 days

Study Arms (4)

Standard Dose oseltamivir adult cohort

ACTIVE COMPARATOR

All participants \>= 15 years will receive standard-dose oseltamivir (75 mg twice daily orally or equivalent dose adjusted for age, weight, and kidney function) for 5 to 10 days.

Drug: Oseltamivir

Double Dose oseltamivir Adult cohort

ACTIVE COMPARATOR

All participants \>= 15 years will receive high-dose oseltamivir (150 mg twice daily orally or equivalent dose adjusted for age, weight, and kidney function) for 5 to 10 days.

Drug: Oseltamivir

Standard Dose Oseltamivir child cohort

ACTIVE COMPARATOR

All participants \<15 years will receive standard-dose oseltamivir (75 mg twice daily orally or equivalent dose adjusted for age, weight, and kidney function) for 5 to 10 days.

Drug: Oseltamivir

Double Dose Oseltamivir child cohort

ACTIVE COMPARATOR

All Participants \<15 years will receive high-dose oseltamivir (150 mg twice daily orally or equivalent dose adjusted for age, weight, and kidney function) for 5 to 10 days.

Drug: Oseltamivir

Interventions

OseltamivirDRUG

Oseltamivir is a sialic acid analogue that potently and specifically inhibits the viral neuraminidases by competitively and reversibly interacting with the active enzyme site of influenza A and B viruses. Oseltamivir will be administered orally in standard formulations (capsules for adults and children at least 15 years of age; suspension for children younger than 15 years).

Also known as: Tamiflu
Double Dose Oseltamivir child cohortDouble Dose oseltamivir Adult cohortStandard Dose Oseltamivir child cohortStandard Dose oseltamivir adult cohort

Eligibility Criteria

Age1 Year+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • At least one of the following respiratory symptoms: cough, dyspnea, sore throat
  • Evidence of severe influenza or avian influenza, as defined below
  • Severe influenza infection criteria:
  • Need for hospitalization
  • One of the following:
  • New infiltrate on chest x-ray (or any infiltrate if no prior chest x-ray or not known)
  • Severe tachypnea (more information on this criterion can be found in the protocol)
  • Severe dyspnea
  • Arterial oxygen saturation of 92% or less on room air by trans-cutaneous method
  • Positive diagnostic testing for influenza, as defined by either rapid influenza antigen (Ag) positive (A or B) or qualitative reverse transcriptase-polymerase chain reaction (RT-PCR) positive for any influenza
  • Illness (defined by onset of fever, respiratory symptoms, or constitutional symptoms) began within 10 days before study enrollment
  • Avian influenza infection criteria:
  • Nasal wash, nasopharyngeal aspirate, endotracheal aspirate, nasal swab, or throat swab that is RT-PCR positive influenza for H5 influenza
  • Illness (defined by onset of fever, respiratory symptoms, or constitutional symptoms) began within 14 days before study enrollment

You may not qualify if:

  • Received more than 72 hours of oseltamivir (six doses) within 14 days
  • Received oseltamivir at higher than standard doses within the last 14 days or during current acute illness, whichever is longer
  • History of allergy or severe intolerance of oseltamivir, as determined by the investigator
  • Alternate explanation for the clinical findings, as determined by the investigator and with the information immediately available
  • Creatine clearance less than 10 ml/minute
  • Pregnant or breastfeeding

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

Changi General Hospital

Singapore, Singapore

Location

National University Hospital, National University of Singapore

Singapore, Singapore

Location

Tan Tock Seng Hospital

Singapore, Singapore

Location

Queen Sirikit National Institute of Child Health

Bangkok, Thailand

Location

Siriraj Hospital Mahidol University

Bangkok, Thailand

Location

Bamrasnaradura Infectious Disease Institute

Nonthaburi, Thailand

Location

Chest Disease Institute

Nonthaburi, Thailand

Location

National Hospital of Pediatrics

Hanoi, Vietnam

Location

National Institute fof Infectious and Tropical Diseases

Hanoi, Vietnam

Location

Children's Hospital #1

Ho Chi Minh City, Vietnam

Location

Hospital for Tropical Diseases

Ho Chi Minh City, Vietnam

Location

Pediatric Hospital #2

Ho Chi Minh City, Vietnam

Location

Related Publications (4)

  • Morse SS. Factors in the emergence of infectious diseases. Emerg Infect Dis. 1995 Jan-Mar;1(1):7-15. doi: 10.3201/eid0101.950102.

    PMID: 8903148BACKGROUND

  • Colman PM. Influenza virus neuraminidase: structure, antibodies, and inhibitors. Protein Sci. 1994 Oct;3(10):1687-96. doi: 10.1002/pro.5560031007.

    PMID: 7849585BACKGROUND

  • de Jong MD, Bach VC, Phan TQ, Vo MH, Tran TT, Nguyen BH, Beld M, Le TP, Truong HK, Nguyen VV, Tran TH, Do QH, Farrar J. Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. N Engl J Med. 2005 Feb 17;352(7):686-91. doi: 10.1056/NEJMoa044307.

    PMID: 15716562BACKGROUND

  • South East Asia Infectious Disease Clinical Research Network. Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial. BMJ. 2013 May 30;346:f3039. doi: 10.1136/bmj.f3039.

    PMID: 23723457RESULT

MeSH Terms

Conditions

Influenza, HumanInfluenza in BirdsDyspnea

Interventions

Oseltamivir

Condition Hierarchy (Ancestors)

Respiratory Tract InfectionsInfectionsOrthomyxoviridae InfectionsRNA Virus InfectionsVirus DiseasesRespiratory Tract DiseasesBird DiseasesAnimal DiseasesRespiration DisordersSigns and Symptoms, RespiratorySigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

AcetamidesAmidesOrganic ChemicalsCyclohexenesCyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbons

Results Point of Contact

Title
Dr. Jeremy Farrar
Organization
Oxford University Clinical Research Unit
info@oucru.org
+84 839237954

Study Officials

  • Tawee Chotpitayasunohdh, MD

    Queen Sirikit National Institute of Child Health, Bangkok, Thailand

    PRINCIPAL INVESTIGATOR

  • Tran Tinh Hien, MD

    Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director, Oxford University Clinical Research Unit

Study Record Dates

First Submitted

March 1, 2006

First Posted

March 1, 2006

Study Start

February 1, 2006

Primary Completion

January 1, 2010

Study Completion

January 1, 2010

Last Updated

June 6, 2014

Results First Posted

May 22, 2014

Record last verified: 2014-05

Locations

TH(4)VN(5)SG(3)