Clinical trial NCT00138294: Control of Epidemic Influenza Through a School-based Influenza Vaccination Program
Official title: Phase 4, School-based, Open-labeled Research Trial for Control of Epidemic Influenza Through a School-based Influenza Vaccination Program in Central Texas.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Influenza
Keywords: influenza vaccine
live attenuated influenza vaccine (LAIV or FluMist)
inactivated influenza vaccine (IIV)
School-based influenza vaccination program
children
herd protection
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: Scott and White Hospital & Clinic
name: Novartis
name: Sanofi Pasteur, a Sanofi Company
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2005-08-30
Enrollment: 29255
Sex: ALL
Minimum age (years): 4
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The main purpose of this study is to learn if influenza vaccines (live attenuated and inactivated influenza vaccines), when given to school-aged children 4 to 18 years of age, can stop or lessen the influenza (flu) outbreak in the community. Another purpose is to show that vaccination of these children will significantly reduce breathing problems (in the vaccinated children and unvaccinated people they come in contact with in the community) that require a visit to the doctor for treatment. Another purpose is to continue to collect safety and flu protection information on live attenuated influenza vaccine (LAIV or FluMist) given to children. The study investigators believe that vaccination of healthy school-aged children is an effective plan for preventing many people in the community from catching the flu. Children will take part in the study for 5 to 10 months.

Detailed description: This study was conducted in three phases. The first phase spanned from 1998-2003 (PubMed ID:14706961; PubMed ID: 12915495) and the second phase spanned from 2003-2007 (PubMedID: 18401289; PubMed ID: 17698577). The final phase of the study spanned 2007-2011 and is the scope of this submission.

The goal of the final phase is to control epidemic influenza through active immunization of healthy school-aged children with the cold-adapted, trivalent, live, attenuated influenza vaccine (LAIV) and at-risk children with the inactivated influenza vaccine (IIV) through a school-based vaccination program.

The hypothesis is that universal vaccination of healthy school-aged children is an alternative and effective strategy for the control of epidemic influenza, and will serve as a model for the control of pandemic influenza and biodefense. The specific aims of the study are: to control the spread of influenza to susceptible adults 35 years of age or older by vaccination of school-aged children 4-18 years of age; to control the spread of influenza to susceptible children and young adults less than 35 years of age by vaccination of school-aged children 4-18 years of age; to develop a school-based vaccination program for rapid and timely delivery of LAIV and IIV to children 4-18 years of age; to demonstrate in school-aged children the direct and total effectiveness of influenza vaccines to reduce the rates of medically attended acute respiratory illness (MAARI) in LAIV and IIV recipients during influenza epidemics; and to capture safety information on LAIV post-licensure.

This is an open-label, up to four year community-based study. In each of the first three study years, school-aged children (4 through 18 years of age) who receive medical care at the Scott \& White Clinics (SWCs), Temple-Belton area, Texas, will be asked to participate in this study. Study participants will receive LAIV or IIV according to their health status. Other children from Temple-Belton area who do not receive medical care at the SWC will be invited to participate in the study and may receive LAIV or IIV. A comparable population enrolled in the SWCs in Waco/McLennan County area and Bryan/College Station will serve as comparison groups.

In the fourth and final year of the study, LAIV will not be provided through the study. However, influenza surveillance will continue and MAARI data will be collected to assess continued protective benefit of influenza vaccines. The final year will also be devoted to completion of data analysis and preparation of manuscripts.

Children 4 years through 8 years who have not previously been vaccinated with an influenza vaccine will be offered a second dose 4 to 6 weeks after the first dose. The influenza vaccines will contain the three influenza virus strains chosen by the FDA. Each subject will receive by nasal spray a 0.2 ml dose (0.1 ml in each nostril) of the LAIV or 0.5 ml intramuscularly.

The duration of each study year is approximately five to ten months, from the time of enrollment (August to January, at the discretion of the investigators) depending on vaccine availability and the timing of influenza activity, to the end of the influenza season (May).

Eligibility criteria: Inclusion Criteria:

* signed informed consent form by adult participant or parent/ legal guardian who are able to understand and comply with the protocol and assent when appropriate (usually age greater than or equal to 7 years)
* healthy subject, 4 through 18 years of age and none of the exclusion criteria

Exclusion Criteria:

* history of hypersensitivity, especially anaphylactic reaction, to any components of FluMist™, including eggs or egg products
* on aspirin therapy or aspirin-containing therapy
* history of Guillain-Barré syndrome
* known or suspected immune deficiency diseases such as combined immunodeficiency, agammaglobulinemia, and thymic abnormalities and conditions such as human immunodeficiency virus infection, malignancy, leukemia or lymphoma
* on immunosuppressive therapies such as systemic corticosteroids, alkylating drugs, antimetabolites, or radiation
* close contact within 21 days after vaccination with immunocompromised individuals
* history of asthma or reactive airway disease
* history of chronic or underlying diseases for which the licensed inactivated flu vaccine (IIV-T) is recommended such as chronic disorders of the cardiovascular and pulmonary systems, or chronic conditions such as metabolic diseases, renal dysfunction or hemoglobinopathies that required medical follow-up or hospitalization during the preceding year
* concurrent use with an anti-influenza compound
* pregnant or plans to become pregnant within 42 days after vaccination
* nursing mother and
* any condition which, in the opinion of the investigator, interferes with evaluation of the vaccine

Primary outcomes:
measure: MAARI Rate During the Epidemic Period (2007-2008)
timeFrame: 12/16/2007 to 3/29/2008 (15 weeks)
measure: MAARI Rate During the Epidemic Period (2008-2009)
timeFrame: 1/4/2009 to 3/21/2009 (11 weeks)
measure: MAARI Rate During the Epidemic and Pandemic Period (2009-2010)
timeFrame: 8/25/09 to 4/3/10 (32 weeks)
Secondary outcomes:
measure: Proportion of SAEs Detected in LAIV Recipients
timeFrame: pre-, post- influenza vaccination
Other outcomes:
Locations:
city: Temple
country: United States
facility: Scott & White Hospital and Clinic
state: Texas
city: Waco
country: United States
facility: Scott & White Hospital and Clinic
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Pedro A Piedra, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gaglani MJ, Piedra PA, Riggs M, Herschler G, Fewlass C, Glezen WP. Safety of the intranasal, trivalent, live attenuated influenza vaccine (LAIV) in children with intermittent wheezing in an open-label field trial. Pediatr Infect Dis J. 2008 May;27(5):444-52. doi: 10.1097/INF.0b013e3181660c2e.
citation: Piedra PA, Gaglani MJ, Kozinetz CA, Herschler GB, Fewlass C, Harvey D, Zimmerman N, Glezen WP. Trivalent live attenuated intranasal influenza vaccine administered during the 2003-2004 influenza type A (H3N2) outbreak provided immediate, direct, and indirect protection in children. Pediatrics. 2007 Sep;120(3):e553-64. doi: 10.1542/peds.2006-2836. Epub 2007 Aug 13.
citation: Halloran ME, Piedra PA, Longini IM Jr, Gaglani MJ, Schmotzer B, Fewlass C, Herschler GB, Glezen WP. Efficacy of trivalent, cold-adapted, influenza virus vaccine against influenza A (Fujian), a drift variant, during 2003-2004. Vaccine. 2007 May 16;25(20):4038-45. doi: 10.1016/j.vaccine.2007.02.060. Epub 2007 Mar 12.
citation: Piedra PA, Gaglani MJ, Riggs M, Herschler G, Fewlass C, Watts M, Kozinetz C, Hessel C, Glezen WP. Live attenuated influenza vaccine, trivalent, is safe in healthy children 18 months to 4 years, 5 to 9 years, and 10 to 18 years of age in a community-based, nonrandomized, open-label trial. Pediatrics. 2005 Sep;116(3):e397-407. doi: 10.1542/peds.2004-2258.
citation: Piedra PA, Gaglani MJ, Kozinetz CA, Herschler G, Riggs M, Griffith M, Fewlass C, Watts M, Hessel C, Cordova J, Glezen WP. Herd immunity in adults against influenza-related illnesses with use of the trivalent-live attenuated influenza vaccine (CAIV-T) in children. Vaccine. 2005 Feb 18;23(13):1540-8. doi: 10.1016/j.vaccine.2004.09.025.
citation: Gaglani MJ, Piedra PA, Herschler GB, Griffith ME, Kozinetz CA, Riggs MW, Fewlass C, Halloran ME, Longini IM Jr, Glezen WP. Direct and total effectiveness of the intranasal, live-attenuated, trivalent cold-adapted influenza virus vaccine against the 2000-2001 influenza A(H1N1) and B epidemic in healthy children. Arch Pediatr Adolesc Med. 2004 Jan;158(1):65-73. doi: 10.1001/archpedi.158.1.65.
citation: Halloran ME, Longini IM Jr, Gaglani MJ, Piedra PA, Chu H, Herschler GB, Glezen WP. Estimating efficacy of trivalent, cold-adapted, influenza virus vaccine (CAIV-T) against influenza A (H1N1) and B using surveillance cultures. Am J Epidemiol. 2003 Aug 15;158(4):305-11. doi: 10.1093/aje/kwg163.
citation: Glezen WP, Gaglani MJ, Kozinetz CA, Piedra PA. Direct and indirect effectiveness of influenza vaccination delivered to children at school preceding an epidemic caused by 3 new influenza virus variants. J Infect Dis. 2010 Dec 1;202(11):1626-33. doi: 10.1086/657089. Epub 2010 Oct 28.