Efficacy Study of Early Versus Late Oseltamivir Administration for Treating and Preventing Influenza - Full Text View

Sponsors and Collaborators:	Marshfield Clinic Research Foundation Centers for Disease Control and Prevention
Information provided by:	Marshfield Clinic Research Foundation
ClinicalTrials.gov Identifier:	NCT00555893

Purpose

This study is a randomized, blinded, placebo-controlled clinical efficacy trial to assess the duration and severity of influenza symptoms, duration of viral shedding, and household transmission in influenza patients receiving oseltamivir early and late relative to placebo.

There are four main hypotheses:

The duration of influenza symptoms, severity, and duration of viral shedding are reduced in patients who start oseltamivir treatment late (48 to 119 hours after illness onset) compared to those receiving no antiviral therapy;
Antiviral effectiveness for reducing infectiousness to household contacts is at least 80% for index cases starting therapy early (<48 hours) compared to those receiving no antiviral therapy;
Antiviral effectiveness for reducing infectiousness to household contacts is at least 60% when patients initiate treatment late (48 to 119 hours) compared to those receiving no antiviral therapy;
Prior influenza vaccination during the same season reduces the duration of influenza symptoms and symptom severity in patients receiving oseltamivir after adjusting for age and timing of antiviral therapy (early vs. late).

There are two secondary hypotheses:

The duration of influenza symptoms, severity, and duration of viral shedding are reduced in patients with influenza who start oseltamivir treatment early (within 48 hours) vs. late (48 to 119 hours);
The incidence of secondary complications is lower in patients starting oseltamivir therapy late relative to those receiving no antiviral therapy.

Condition	Intervention
Influenza	Drug: Oseltamivir Drug: Placebo

MedlinePlus related topics: Flu

Drug Information available for: Oseltamivir Tamiflu

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Monitoring Influenza Severity and Transmission on Tamiflu (MISTT)

Further study details as provided by Marshfield Clinic Research Foundation:

Primary Outcome Measures:

Duration of influenza illness [ Time Frame: Interval (in 12 hour blocks) from symptom onset until resolution ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Mean Illness Severity Score [ Time Frame: Calculated from initial enrollment (randomization) up to first period of symptom resolution ] [ Designated as safety issue: No ]
Duration of viral shedding [ Time Frame: Interval (in days) from collection of the first sample yielding a positive influenza test to the last sample yielding a positive culture ] [ Designated as safety issue: No ]
Secondary Attack Rate (number of influenza episodes confirmed by polymerase chain reaction in household members of index cases, divided by the total number of household members at-risk) [ Time Frame: Household members with symptom onset on days 1 through 7 after index case randomization ] [ Designated as safety issue: No ]
Antiviral effectiveness for reducing infectiousness (based on symptomatic, laboratory-confirmed influenza infections in household contacts) [ Time Frame: Days 1 through 7 after index case randomization ] [ Designated as safety issue: No ]
Secondary complications (new clinical diagnosis of acute otitis media, acute sinusitis or pneumonia)documented in medical record, or influenza-related hospital admission [ Time Frame: From 0 to 28 days after randomization ] [ Designated as safety issue: No ]
Mean influenza well-being score (health, ability to perform usual activities and sleep quality) [ Time Frame: Interval from randomization up to and including first day of symptom resolution ] [ Designated as safety issue: No ]

Estimated Enrollment:	400
Study Start Date:	January 2008
Estimated Study Completion Date:	April 2009
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Drug: Experimental	Drug: Oseltamivir Dosing is per manufacturer's recommended dose. Adults and adolescents weighing greater than 88 pounds will receive 75 mg oseltamivir capsule twice daily for 5 days (10 doses). Participants one year of age and older up to a maximum of 88 pounds will receive a liquid form of study medication containing oseltamivir at a concentration of 15 mg/mL. The dose will be based on weight as follows: < 34 pounds,2 mL doses, two times per day; 34 - 51 pounds, 3 mL doses, two times per day; 52-88 pounds, 4 mL doses, two times per day.
Placebo: Placebo Comparator	Drug: Oseltamivir Dosing is per manufacturer's recommended dose. Adults and adolescents weighing greater than 88 pounds will receive 75 mg oseltamivir capsule twice daily for 5 days (10 doses). Participants one year of age and older up to a maximum of 88 pounds will receive a liquid form of study medication containing oseltamivir at a concentration of 15 mg/mL. The dose will be based on weight as follows: < 34 pounds,2 mL doses, two times per day; 34 - 51 pounds, 3 mL doses, two times per day; 52-88 pounds, 4 mL doses, two times per day. Drug: Placebo Identical placebo capsule twice daily for 5 days (10 doses). Participants one year of age and older up to a maximum of 88 pounds will receive a placebo syrup. The dose will be based on weight as follows: < 34 pounds,2 mL doses, two times per day; 34 - 51 pounds, 3 mL doses, two times per day; 52-88 pounds, 4 mL doses, two times per day.

Arms

Assigned Interventions

Active Drug: Experimental

Drug: Oseltamivir

Dosing is per manufacturer's recommended dose. Adults and adolescents weighing greater than 88 pounds will receive 75 mg oseltamivir capsule twice daily for 5 days (10 doses). Participants one year of age and older up to a maximum of 88 pounds will receive a liquid form of study medication containing oseltamivir at a concentration of 15 mg/mL. The dose will be based on weight as follows: < 34 pounds,2 mL doses, two times per day; 34 - 51 pounds, 3 mL doses, two times per day; 52-88 pounds, 4 mL doses, two times per day.

Placebo: Placebo Comparator

Drug: Oseltamivir

Dosing is per manufacturer's recommended dose. Adults and adolescents weighing greater than 88 pounds will receive 75 mg oseltamivir capsule twice daily for 5 days (10 doses). Participants one year of age and older up to a maximum of 88 pounds will receive a liquid form of study medication containing oseltamivir at a concentration of 15 mg/mL. The dose will be based on weight as follows: < 34 pounds,2 mL doses, two times per day; 34 - 51 pounds, 3 mL doses, two times per day; 52-88 pounds, 4 mL doses, two times per day.

Drug: Placebo

Identical placebo capsule twice daily for 5 days (10 doses). Participants one year of age and older up to a maximum of 88 pounds will receive a placebo syrup. The dose will be based on weight as follows: < 34 pounds,2 mL doses, two times per day; 34 - 51 pounds, 3 mL doses, two times per day; 52-88 pounds, 4 mL doses, two times per day.

Detailed Description:

In the past decade influenza has become increasingly recognized as a serious disease and pandemic threat. Elderly persons, young children, and individuals with chronic medical conditions have the greatest risk for complications or death from influenza infection. Neuraminidase inhibitors are currently licensed for the treatment and prevention of influenza if started early in the course of illness, but little is known regarding the effects of oseltamivir (one neuraminidase inhibitor) on illness severity and household transmission when initiated later in the course of illness. Greater knowledge of both the treatment effects and the efficacy for reducing influenza transmission is urgently needed for optimal management of seasonal influenza, and to maximize use of a limited stockpile of antiviral drugs in the event of an influenza pandemic.

Eligibility

Ages Eligible for Study:	1 Year to 79 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Outpatient encounter for acute respiratory illness less than 5 days duration;
Acute respiratory illness with feverishness, chills or cough;
Access to internet or telephone at home;
Residence in Marshfield Epidemiologic Study Area (14 zip code area in central WI).

Exclusion Criteria:

Institutional resident;
Self-reported chronic liver or kidney disease;
Pregnancy or breast-feeding;
Prior hypersensitivity to oseltamivir;
Dementia, impaired communication or other reason for inability to provide informed consent;
Immunocompromised status (HIV infection, neutropenia, systemic corticosteroid use or other immunosuppressive drugs in past 30 days);
Patient received 1 or more doses of influenza antiviral agent or a prescription for one of these drugs prior to enrollment.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00555893

Locations

United States, Wisconsin
Marshfield Clinic Research Foundation
Marshfield, Wisconsin, United States, 54449

Sponsors and Collaborators

Marshfield Clinic Research Foundation

Centers for Disease Control and Prevention

Investigators

Principal Investigator:

Edward Belongia, MD

Marshfield Clinic Research Foundation

More Information

Responsible Party:	Marshfield Clinic Research Foundation ( Edward Belongia, Senior Research Scientist; Director Epidemiology Research Center )
Study ID Numbers:	1 UO1 IP000124-01
Study First Received:	November 7, 2007
Last Updated:	January 13, 2009
ClinicalTrials.gov Identifier:	NCT00555893
Health Authority:	United States: Institutional Review Board

Keywords provided by Marshfield Clinic Research Foundation:

randomized
blinded
controlled
efficacy

Study placed in the following topic categories:

Virus Diseases
Respiratory Tract Diseases
Respiratory Tract Infections

Influenza, Human
Orthomyxoviridae Infections
Oseltamivir

Additional relevant MeSH terms:

Anti-Infective Agents
RNA Virus Infections
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses

Enzyme Inhibitors
Antiviral Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009