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Trial registered on ANZCTR


Trial ID
ACTRN12610000361000
Ethics application status
Approved
Date submitted
24/03/2010
Date registered
6/05/2010
Date last updated
6/05/2010
Type of registration
Retrospectively registered

Titles & IDs
Public title
An unblinded randomized study of influenza A/H1N1 2009 (swine flu)resistance under standard and extended duration Oseltamivir treatment
Scientific title
An unblinded randomised study to evaluate viral resistance (viral shredding) following standard and extended duration Oseltamivir treatment in patients with influenza A/H1N1 2009
Secondary ID [1] 1548 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
influenza A/H1N1 2009 243489 0
Condition category
Condition code
Infection 239789 239789 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Adults or subjects >40 kg will be randomised in a ratio of 1:1 to a standard 75mg twice a day for 5 days or an extended 75mg tiwice a day for 10 days. The mode of adminstration is an oral capsule
Children will be randomised in a ratio of 1:1 to a standard dose for 5 days or an extended dose for 10 days powder for oral suspension, which when reconstituted with water to a concentration of 1.2% contains 12 mg/mL oseltamivir. The dose is calculated by weight.
15 kg or less 60 mg per day divided into 2 doses
15–23 kg 90 mg per day divided into 2 doses
24–40 kg 120 mg per day divided into 2 doses
Intervention code [1] 237108 0
Treatment: drugs
Comparator / control treatment
Adults and subjects >40kg in the standard (control) group will receive Oseltamivir as an oral capsule 75mg twice per day for 5 days.
Subjects 40kg or less in the standard (control) will receive a powder for oral suspension, which when reconstituted with water to a concentration of 1.2% contains 12 mg/mL oseltamivir. The dose is calculated by weight.
15 kg or less 60 mg per day divided into 2 doses
15–23 kg 90 mg per day divided into 2 doses
24–40 kg 120 mg per day divided into 2 doses
Control group
Dose comparison

Outcomes
Primary outcome [1] 240558 0
The difference in the proportion of patients shedding virus with each duration and the proportion which exhibit resistance. Nasopharyngeal swabs will be obtained from both nostrils. The specimens will be analyzed for influenza viruses by polymerase chain reaction (PCR) methods within 48 hrs.
Timepoint [1] 240558 0
9 days (window +1 days) post screening/randomisation visit which is day 0
Secondary outcome [1] 257148 0
Differences in reduction of viral load, measured at days 5 and 10, in subjects given standard and extended duration oseltamivir. For subjects that are PCR positive, phenotypic viral sensitivity to oseltamivir will be determined by means of the NA Star neuraminidase chemilumiscent assay. In instances where resistance is detected, sequencing of the viral genome will be undertaken to identify the relevant resistance mutations.
Timepoint [1] 257148 0
At 5 days and 9 days (window +1 days) screening/randomisation visit which is day 0

Eligibility
Key inclusion criteria
1. Male and non-pregnant female subjects age greater than or equal to 5 years:

2. A positive Influenza A Rapid Antigen Test (RAT) performed on an adequate nasopharyngeal specimen, in accordance with the manufacturer’s instructions. If the RAT is negative but, in the investigator’s opinion, there is strong clinical suspicion of any type of influenza then the subject may be enrolled.
3. Presence of fever at the time of screening of greater or equal to 37.8 degrees celius (greater or equal to 100.04 degrees F) taken orally. A subject self-report of a history of a fever or feverishness within the 24 hours prior to screening will also qualify for enrolment in the absence of documented fever at the time of screening.
4. Presence of at least one respiratory symptom (cough, sore throat, or nasal symptoms).
5. Onset of symptoms no more than 48 hours before presentation for screening.
6. Female of non-childbearing potential, either surgically sterilised or at least one year post-menopausal. If a female is of childbearing potential, she must be abstinent or using adequate contraceptive precautions, including but not limited to the following: barrier methods (condom or diaphragm), intrauterine contraceptive device (IUCD), oral contraceptive, or equivalent hormonal contraceptive (e.g. progesterone-only implant, cutaneous hormonal patch, injectable contraceptives) and agree to continue such precautions for the duration of the study.
7. Written informed consent.
Minimum age
5 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Women who are pregnant or breast-feeding.
2. Presence of clinically significant signs of acute respiratory distress
3. History of severe chronic obstructive pulmonary disease (COPD).
4. History of heart failure of angina requiring daily pharmacotherapy with symptoms consistent with New York Heart Association Class III or IV functional status within the past 12 months.
5. History of chronic renal impairment requiring hemodialysis and/or known or suspected to have moderate or severe renal impairment (actual or estimated creatinine clearance <50mL/min).
6. Clinical evidence of worsening of any chronic medical condition (temporarily associated with the onset of symptoms of influenza) which, in the investigator’s opinion, indicated that such finding(s) could represent complications of influenza.
7. Current clinical evidence, including clinical signs and/or symptoms consistent with otitis, bronchitis, sinusitis and/or pneumonia, or active bacterial infection at any body site that requires therapy with oral or systemic antibiotics.
8. Presence of immunocompromised status due to chronic illness, previous organ transplant, or use of immunosuppressive medical therapy which would include oral or systemic treatment with >10 mg prednisone or equivalent on a daily basis within 30 days of screening.
9. Currently receiving treatment for viral hepatitis B or viral hepatitis C.
10. Presence of known Human immunodeficiency virus (HIV).
11. History of alcohol abuse or drug addiction within 1 year prior to admission in the study.
12. Current participation in a study of any investigational drug.
13. Any other medical condition which, in the opinion of the investigator, would preclude safe participation in the clinical trial.
14. Known hypersensitivity to Oseltamivir.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomisation table created by a computer software (i.e., computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Current
Final
Recruitment outside Australia
Country [1] 1944 0
New Zealand
State/province [1] 1944 0

Funding & Sponsors
Funding source category [1] 237481 0
Commercial sector/Industry
Name [1] 237481 0
Roche Products NZ Ltd
Address [1] 237481 0
8 Henderson Place
Te Papapa
Auckland 1061
Country [1] 237481 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Roche Products NZ Ltd
Address
8 Henderson Place
Te Papapa
Auckland 1061
Country
New Zealand
Secondary sponsor category [1] 236965 0
Commercial sector/Industry
Name [1] 236965 0
Southern Clinical Trials Ltd
Address [1] 236965 0
3 Strickland Street
Beckenham
Christchurch 8024
Country [1] 236965 0
New Zealand
Other collaborator category [1] 814 0
Hospital
Name [1] 814 0
Canterbury Health Laboratories
Address [1] 814 0
Corner Hagley Ave and Tuam Street,
P O Box 151,
Christchurch, 8140,
Country [1] 814 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258714 0
Upper South A Regional Ethics Committee
Ethics committee address [1] 258714 0
Ministry of Health
4th Floor, 250 Oxford Tce
PO Box 3877
Christchurch 8140
Ethics committee country [1] 258714 0
New Zealand
Date submitted for ethics approval [1] 258714 0
08/06/2009
Approval date [1] 258714 0
23/07/2009
Ethics approval number [1] 258714 0
URA/09/06/046

Summary
Brief summary
The study will show whether the influenza virus is more likely to develop resistance to Tamiflu during treatment while using a standard 5 day course compared with an extended 10 day course.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30032 0
Address 30032 0
Country 30032 0
Phone 30032 0
Fax 30032 0
Email 30032 0
Contact person for public queries
Name 13279 0
Dr Simon Carson
Address 13279 0
Southern Clinical Trials Ltd
PO Box 33227
Barrington
Christchurch 8244
Country 13279 0
New Zealand
Phone 13279 0
+64 3 337 1979
Fax 13279 0
+64 3 337 1974
Email 13279 0
simon@sctrials.co.nz
Contact person for scientific queries
Name 4207 0
Dr Lance Jennings
Address 4207 0
Canterbury Health Laboratories
PO Box 151
Cnr Hagley Ave and Tuam St
Christchurch 8140
Country 4207 0
New Zealand
Phone 4207 0
+64 3 364-0075
Fax 4207 0
+64 3 364-0750
Email 4207 0
lance.jennings@cdhb.govt.nz