Protocol Number: 06-I-0106

Title:

High Dose Versus Standard-Dose Oseltamivir for the Treatment of Severe Influenza and Avian Influenza: A Phase II Double-Blind, Randomized Clinical Trial

Number:

06-I-0106

Summary:

This study will compare the standard dose of the anti-influenza drug Tamiflu with a higher dose of the drug to see if the higher dose is more effective in treating severe influenza or avian influenza (bird flu) infections. The National Institutes of Health (NIH) is one of several international sites for this study.

People 18 years of age and older with severe influenza infection requiring hospitalization or with avian influenza infections may be eligible for this study. Candidates are screened with a nasal swab, throat swab and nasal wash to look for virus. For the nasal wash, a small amount of salt water is squirted in the nose and removed by suction.

Participants are randomly assigned to receive either the standard dose or higher dose of Tamiflu. They take the medication twice a day for 5 days. Patients who are still very ill at 5 days and meet certain conditions are given the medicine for another 5 days. Patients are admitted to the hospital, in isolation, for the duration of treatment. In addition to treatment, patients have the following tests and procedures:

-Nose and throat swabs, nasal wash, rectal swab, blood and urine tests and chest x-ray before starting treatment

-Blood draws on study days 1, 3, 5 and 7

-Nose and throat swabs every day for the first 5 days and on days 10, 14 and 28

-Rectal swabs days every day for the first 5 days and on days 10, 14 and 28

Patients with bird flu are seen in the clinic at 2 and 6 months. A repeat blood test is done at 6 months.

Sponsoring Institute:

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

1. Age greater than or equal to 1 year

AND

2. At least one respiratory symptom:

- Cough

- Dyspnea (shortness of breath)

- Sore throat

AND

3. Have evidence of severe influenza and avian influenza as defined below (A or B)

A. Evidence of severe influenza infection:

- 1. Need for hospitalization (as determined by investigator or clinician)

AND

- 2. One of the following: (all criteria as judged by the investigator)

- New infiltrate on chest X-ray (or any infiltrate if no prior chest X-ray or not known)

- Severe tachypnea (respiratory rate greater than or equal to 30 for ages greater than or equal to 12 years, rate greater than or equal to 40 for ages 6 to 12 years, rate greater than or equal to 45 for ages 3 to 6 years, rate greater than or equal to 50 for ages 1 to 3 years)

- Severe dyspnea (unable to speak full sentences, or use of accessory respiratory muscles)

- Arterial oxygen saturation less than or equal to 92% on room air by trans-cutaneous method

AND

- 3. Positive diagnostic testing for influenza defined as (one of the following)

- Rapid influenza antigen (Ag) positive (A or B)

- Qualitative RT-PCR positive for influenza (any)

AND

- 4. Illness (onset of fever, respiratory symptoms, or constitutional symptoms) began within the 10 days prior to enrollment

B. Evidence of avian influenza infection

1. Nasal wash, nasopharyngeal aspirate, endotracheal aspirate, nasal swab, or throat swab that is RT-PCR positive influenza for H5 influenza

AND

2. Illness (onset of fever, respiratory symptoms, or constitutional symptoms) began within the 14 days prior to enrollment

EXCLUSION CRITERIA (any of the following):

1. Pregnancy or urine beta-hCG positive.

2. Females who are actively breast feeding.

3. Receipt of more than 72 hours of oseltamivir (six doses) within the last 14 days.

4. Receipt of oseltamivir at higher than standard doses (75 mg bid, or equivalent dose adjusted for age, weight and creatinine clearance) within the last 14 days or during this acute illness, whichever is longer.

5. History of allergy or severe intolerance of oseltamivir as determined by the investigator.

6. Alternate explanation for the clinical findings as determined by the investigator with the information immediately available.

7. Creatinine Clearance (estimated by serum Cr) less than 10 ml/min.

Special Instructions:

NIH Site Specific: recruitment age greater than or equal to 18 years.

Keywords:

Antibody Response

Antiviral Efficacy

Bird Flu

Severe Respiratory Distress

Viral Replication and Shedding

Recruitment Keyword(s):

Influenza

Avian Influenza

Bird Flu

Condition(s):

Avian Influenza

Severe Influenza

Investigational Drug(s):

Oseltamivir

Investigational Device(s):

None

Intervention(s):

Drug: Oseltamivir

Supporting Site:

National Institute of Allergy and Infectious Diseases

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Morse SS. Factors in the emergence of infectious diseases. Emerg Infect Dis. 1995 Jan-Mar;1(1):7-15. Review.

Colman PM. Influenza virus neuraminidase: structure, antibodies, and inhibitors. Protein Sci. 1994 Oct;3(10):1687-96. Review.

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.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home

National Institutes of Health Clinical Center Bethesda, Maryland 20892. Last update: 09/15/2008