Oseltamivir Randomised Controlled Efficacy Trial

NCT00707941 | Completed Phase 3 DMC

• 2 other identifiers: 2008-0071U01IP000127-01
• Study Type: interventional
• Target: 1,190
• Locations: 1 country
• Sites: 1

Brief Summary

Background In preparation for a global influenza pandemic, there is an urgent need for representative data from populations and settings where the pandemic is most likely to arise. There are no data on oseltamivir efficacy from Asian urban slum populations concerning duration of illness and viral shedding, nor whether efficacy depends on starting treatment \< 48 hours or ≥ 48 hours after illness onset. Finally, there are no data on the capacity of the drug, in such settings, to affect household and community transmission rates. Aims and Objectives This proposal aims to compare the duration of clinical illness among patients treated with oseltamivir vs placebo \< 48 hours and ≥ 48 hours after illness onset. It will compare the duration of viral shedding among all treatment groups vs placebo, risk of transmission to household contacts by treatment group and whether neuraminidase inhibitor use creates resistance. Secondarily it aims to measure the effect on influenza. Design and Methods A double-blind placebo controlled clinical trial design among a population in an urban slum under current influenza disease burden surveillance will be enrolled. Infection status will be confirmed by rRT-PCR. Patients ≥ 1 year old will be randomised to \< 48 hour and ≥ 48 hour treatment arms. Family members and neighbours will also be assessed by PCR and a basic reproductive number calculated (R0). Relevance These findings will address whether oseltamivir can affect illness duration and severity, affect transmission, incidence and resistance in high risk urban Asian settings where a pandemic is most likely to arise.

Conditions

Influenza; Pneumonia; Lower Respiratory Tract Infection; Upper Respiratory Tract Infection; Viral Shedding

Keywords

Influenza like illness; Pneumonia; Bronchiolitis; Upper respiratory tract illness; Otitis media; Viral shedding; Nasopharyngeal wash; Viral culture; PCR

Outcome Measures

Primary Outcomes (5)

• Duration of clinical illness among patients treated with oseltamivir vs placebo < 48 hours as well as ≥48 hours after illness onset

  18 months

• Duration of viral shedding among all treatment groups vs placebo

  18 months

• Compare the risk of transmission to household contacts by treatment group vs placebo

  18 months

• The effect of neuraminidase inhibitor use on the emergence of resistance

  18 months

• Clinical complications associated with influenza among all treatment groups vs placebo

  18 months

Secondary Outcomes (3)

• Effect of acute neuraminidase inhibitor treatment on influenza incidence in the population

  18 months

• Transmission of resistant mutations within households

  18 months

• Viral shedding in stool and effect of oseltamivir on stool shedding if present

  18 months

Study Arms (4)

1

EXPERIMENTAL

Oseltamivir for 5 days for patients with illness duration \< 48 hours

Drug: Oseltamivir

2

PLACEBO COMPARATOR

Placebo for 5 days for patients with illness duration \< 48 hours

Drug: Placebo

3

EXPERIMENTAL

Oseltamivir for 5 days for patients with illness duration ≥ 48 hours

Drug: Oseltamivir

4

PLACEBO COMPARATOR

Placebo for 5 days for patients with illness duration ≥ 48 hours

Drug: Placebo

Interventions

Oseltamivir DRUG

Children ≤12 years: Suspension by Weight (Kg) as follows: Dose X 5 days Volume (ml) \< 15kg = 30 mg PO BID (2.5 ml) 15kg - 22kg = 45 mg PO BID (3.75 ml) 23kg - 39kg = 60 mg PO BID (5 ml) Patients≥12 years: 75 mg capsules as follows: 1 cap (75 mg) PO BID X 5 days ≥ 40 75 mg PO BID 6.25

1; 3

Placebo DRUG

Children \< 12 years, suspension by weight (kg) as follows: Dose X 5 days Volume (ml) \< 15kg = 30 mg PO BID (2.5 ml) 15kg - 22kg = 45 mg PO BID (3.75 ml) 23kg - 39kg = 60 mg PO BID (5 ml) Patients≥12 years: 75 mg capsules as follows 1 cap (75 mg) PO BID X 5 days ≥ 40 75 mg PO BID 6.25

2; 4

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Persons at least one year old residing in randomly selected households with at least one major illness sign, or if absent at least two minor illness signs who are rapid test positive for either influenza A or influenza B.

You may not qualify if:

• Persons with a history of non-febrile convulsions or
• Persons who are taking anticonvulsive agents, or
• Persons who have a nonrespiratory comorbid condition requiring immediate medical intervention, or
• Persons who are pregnant.

Sponsors & Collaborators

• International Centre for Diarrhoeal Disease Research, Bangladesh: lead
• Centers for Disease Control and Prevention: collaborator

Study Sites (1)

Kamalapur Urban Site, ICDDR,B

Dhaka, 1000, Bangladesh

Location

Related Publications (5)

• Abdullah Brooks W, Terebuh P, Bridges C, Klimov A, Goswami D, Sharmeen AT, Azim T, Erdman D, Hall H, Luby S, Breiman RF. Influenza A and B infection in children in urban slum, Bangladesh. Emerg Infect Dis. 2007 Oct;13(10):1507-8. doi: 10.3201/eid1310.070368. No abstract available.

  PMID: 18257997 BACKGROUND

• Abdullah Brooks W, Erdman D, Terebuh P, Klimov A, Goswami D, Sharmeen AT, Azim T, Luby S, Bridges C, Breiman R. Human metapneumovirus infection among children, Bangladesh. Emerg Infect Dis. 2007 Oct;13(10):1611-3. doi: 10.3201/eid1310.070337.

  PMID: 18258022 BACKGROUND

• Brooks WA, Breiman RF, Goswami D, Hossain A, Alam K, Saha SK, Nahar K, Nasrin D, Ahmed N, El Arifeen S, Naheed A, Sack DA, Luby S. Invasive pneumococcal disease burden and implications for vaccine policy in urban Bangladesh. Am J Trop Med Hyg. 2007 Nov;77(5):795-801.

  PMID: 17984328 BACKGROUND

• Fry AM, Goswami D, Nahar K, Sharmin AT, Rahman M, Gubareva L, Trujillo A, Barnes J, Azim T, Bresee J, Luby SP, Brooks WA. Effects of oseltamivir treatment of index patients with influenza on secondary household illness in an urban setting in Bangladesh: secondary analysis of a randomised, placebo-controlled trial. Lancet Infect Dis. 2015 Jun;15(6):654-62. doi: 10.1016/S1473-3099(15)70041-1. Epub 2015 Mar 16.

  PMID: 25788164 DERIVED

• Fry AM, Goswami D, Nahar K, Sharmin AT, Rahman M, Gubareva L, Azim T, Bresee J, Luby SP, Brooks WA. Efficacy of oseltamivir treatment started within 5 days of symptom onset to reduce influenza illness duration and virus shedding in an urban setting in Bangladesh: a randomised placebo-controlled trial. Lancet Infect Dis. 2014 Feb;14(2):109-18. doi: 10.1016/S1473-3099(13)70267-6. Epub 2013 Nov 22.

  PMID: 24268590 DERIVED

Related Links

• Click here for more information about ICDDR,B
• Click here for more information about seasonal and pandemic influenza

MeSH Terms

Conditions

Influenza, Human; Pneumonia; Respiratory Tract Infections; Bronchiolitis; Otitis Media

Interventions

Oseltamivir

Condition Hierarchy (Ancestors)

Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchitis; Bronchial Diseases; Lung Diseases, Obstructive; Otitis; Ear Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• W. Abdullah Brooks, MD, MPH

  International Centre for Diarrhoeal Disease Research, Bangladesh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2008
• First Posted: July 1, 2008
• Study Start: May 1, 2008
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: June 6, 2018

Record last verified: 2008-06

Locations

BA (1)