Clinical trial NCT01056354: Respiratory Virus Outpatient Study (FLU 002 Plus)
Official title: An International Observational Study to Characterize Adults With Influenza or Other Targeted Respiratory Viruses
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Influenza and Other Novel Respiratory Viruses
Keywords: Influenza
respiratory virus
pandemic
swine flu
infection
MERS-CoV
SARS-CoV
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: National Institutes of Health (NIH)
First posted: 2010-01-26
Enrollment: 11719
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Persons who seek medical care and are suspected of having influenza or a targeted novel respiratory virus\* of major public health concern will be enrolled at numerous participating clinical sites on several continents.

\*The current list of other targeted novel respiratory viruses includes MERS-CoV and SARS-CoV.

Brief summary: Following the sudden and unexpected emergence of influenza A(H1N1)pdm09 (2009 H1N1) virus, this observational study was initiated to describe participants seeking medical care in geographically diverse locations with 2009 H1N1 infection and their clinical course over a 14-day period following enrollment. In 2011, as surveillance indicated that 2009 H1N1 virus was co-circulating with other seasonal influenza A and B viruses worldwide, the protocol was expanded to include other influenza A subtypes and influenza B viruses. This version of the protocol further broadens the scope of this observational study. With the recognition that novel respiratory viruses other than novel influenza A viruses, e.g., Middle East Respiratory Syndrome Coronavirus (MERS-CoV), could become prevalent and of major public health importance, the objectives of this protocol have been expanded

Detailed description: The purpose of this observational study is to describe participants in geographically diverse locations with influenza virus infection and other viral respiratory diseases of public health importance and their clinical course over a 14-day period following enrollment.

Specific objectives related to influenza virus infection are to estimate the percentage of participants who go on to develop severe disease or complications that require hospitalization; to obtain information on risk factors for disease severity; and to establish a central repository of specimens for use in virus characterization, including subtyping, antigenic and genetic analyses, identification of signature mutations associated with antiviral drug resistance, mutational evolution, and additional reassortment.

Specific objectives related to novel non-influenza respiratory viruses of potential major public health importance are to characterize initial cases and their outcomes in order to develop more specific protocols that could inform the prevention and treatment of these new infections

Sample size is open-ended for this observational study. Based on experience to date, it is estimated that 75 sites will participate and will enroll approximately 1,700 patients with influenza each year, about one-half in the Northern Hemisphere and one-half in the Southern Hemisphere. Sites in diverse geographic locations on several continents will participate.

Study Plan:

* Participants who meet the eligibility criteria will be enrolled at participating clinical sites.
* At enrollment, consent is signed and information (demographics, medical history (including prior influenza and pneumococcal vaccination), medications (including antivirals) and treatments prescribed will be recorded. A blood sample for serum and plasma will be obtained at enrollment, as well as an upper respiratory tract specimen. The respiratory specimen will be sent for central reverse transcriptase polymerase chain reaction (RT-PCR) testing for influenza.
* Status will be re-assessed at approximately 14 days after enrollment and another blood sample for serum and plasma will be obtained. For participants with a confirmed novel respiratory virus of public health importance, attempts will be made to obtain a sample of the local specimen used to diagnose the infection.

In February 2012, the FLU 004 Genomics protocol v 1.0 was released to the field.

In August 2013 v 2.0 of the protocol was released as INSIGHT Genomics. The protocol was expanded beyond the FLU 002 and FLU 003 studies to include all qualifying INSIGHT studies (list posted on the INSIGHT website, www.insight-trials.org. The purpose of this substudy is to obtain a whole blood sample from which DNA will be extracted to study polymorphisms in immune response genes and other genetic variants that may be associated with an increased risk of disease progression among individuals with infectious diseases of public health importance who are enrolled in qualifying INSIGHT studies.

Participating FLU 002 Plus sites are given the option to also participate in INSIGHT Genomics, which requires a separate protocol registration. Participants, once consented to FLU 002 Plus, will be offered the option to also consent to INSIGHT Genomics, which includes a single whole blood sample collection. Participation in FLU 002 Plus will not be compromised if a participant opts not to participate in INSIGHT Genomics.

Eligibility criteria: Inclusion Criteria:

* Be ≥ 18 years of age
* Have a signed informed consent by participant
* Have a fever (37.8 degrees C (100 degrees F) or higher on examination or patient-reported fever (37.8 degrees C (100 degrees F) or higher, or feverishness (felt febrile but did not take temperature) in the past 24 hours.
* Have a cough and/or sore throat
* Have suspected influenza or a suspected targeted non-influenza viral respiratory infection

Exclusion Criteria:

- Current imprisonment, or compulsory detention (involuntary incarceration) for treatment of a psychiatric or physical illness.

Primary outcomes:
measure: Death or Hospitalization
timeFrame: 14-day period following enrollment
Secondary outcomes:
measure: Days of work/school lost, duration of symptoms, use of antivirals
timeFrame: 14 days
Other outcomes:
Locations:
city: San Diego
country: United States
facility: UCSD Antiviral Research Center
state: California
city: Denver
country: United States
facility: Denver Public Health
state: Colorado
city: Washington, D.C.
country: United States
facility: George Washington Medical Faculty Associates
state: District of Columbia
city: Washington, D.C.
country: United States
facility: Washington DC VA Medical Center
state: District of Columbia
city: Pensacola
country: United States
facility: Infectious Diseases Associates NW FL, PA
state: Florida
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Southfield
country: United States
facility: Newland Immunology Center of Excellence (NICE)
state: Michigan
city: Newark
country: United States
facility: New Jersey Medical School Adult Clinical Research Center
state: New Jersey
city: New York
country: United States
facility: Cornell CRS
state: New York
city: The Bronx
country: United States
facility: Bronx-Lebanon Hospital Center
state: New York
city: Chapel Hill
country: United States
facility: UNC AIDS Clinical Trials Unit
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Chattanooga
country: United States
facility: University of Tennessee College of Medicine
state: Tennessee
city: Fort Worth
country: United States
facility: University of North Texas Health Science Center
state: Texas
city: Houston
country: United States
facility: Houston AIDS Research Team
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: El Palomar
country: Argentina
facility: Hospital Nacional Profesor Alejandro Posadas
state: Buenos Aires
city: La Matanza
country: Argentina
facility: Hospital Interzonal General de Agudos Dr. Diego Paroissien
state: Buenos Aires
city: La Plata
country: Argentina
facility: Instituto Medico Platense
state: Buenos Aires
city: Vicente Lopez
country: Argentina
facility: Hospital Profesor Bernardo Houssay
state: Buenos Aires
city: Rosario
country: Argentina
facility: CAICI (Instituto Centralizado de Assistencia e Investigacion Clinica Integral)
state: Santa Fe
city: Rosario
country: Argentina
facility: Sanatorio Britanico
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: CEMIC
city: Buenos Aires
country: Argentina
facility: FUNCEI
city: Buenos Aires
country: Argentina
facility: Hospital General de Agudos JM Ramos Mejia
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Cordoba
country: Argentina
facility: Hospital Privado Centro Medico de Cordoba
city: Cordoba
country: Argentina
facility: Hospital Rawson
city: Canberra
country: Australia
facility: Interchange General Practice
state: Australian Capital Territory
city: Darlinghurst
country: Australia
facility: Holdsworth House Medical Practice
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: Prahran Market Clinic
state: Victoria
city: North Fitzroy
country: Australia
facility: Northside Clinic
state: Victoria
city: Brussels
country: Belgium
facility: Centre Hospitalier Universitaire St. Pierre (C.H.U. St. Pierre)
city: Tessenderlo
country: Belgium
facility: Practimed Medisch Centrum Tessenderlo
city: Santiago
country: Chile
facility: Clinica Alemana
city: Santiago
country: Chile
facility: Fundacion Arriaran
city: Santiago
country: Chile
facility: Pontificia Universidad Catolica de Chile
city: Aarhus
country: Denmark
facility: Arhus Universitetshospital, Skejby
city: Copenhagen
country: Denmark
facility: CHIP
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Infektionsmedicinsk ambulatorium 8622
city: Copenhagen
country: Denmark
facility: University Clinic of General Practice
city: Tallinn
country: Estonia
facility: West Tallinn Central Hospital Infectious Diseases
city: Bonn
country: Germany
facility: Medizinische Universitatsklinik - Bonn, Immunologische Ambulanz CRS
city: Cologne
country: Germany
facility: Klinik I fur Innere Medizin der Universitat zu Koln, Studienburo fur Infektiologie u. HIV
city: Frankfurt
country: Germany
facility: Johann Wolfgang Goethe - University Hospital, Infektionsambulanz CRS
city: Hamburg
country: Germany
facility: Ifi - Studien und Projekte GmbH
city: Athens
country: Greece
facility: 1st Dept of Critical Care Medicine and Pulmonary Services, Evangelismos Hospital
city: Athens
country: Greece
facility: 1st Respiratory Medicine Dept, Athens Hosp for Diseases of the Chest "Sotiria Hospital"
city: Athens
country: Greece
facility: Evangelismos General Hospital
city: Athens
country: Greece
facility: Hippokration University General Hospital of Athens
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center
city: Lima
country: Peru
facility: Hospital Nacional Arzobispo Loayza
city: Lima
country: Peru
facility: Asociacion Civil IMPACTA Salud y Educacion
city: Lima
country: Peru
facility: Hospital Nacional Edgardo Rebagliati Martins
city: Lima
country: Peru
facility: Hospital Nacional Guillermo Almenara Irigoyen
city: Warsaw
country: Poland
facility: Wojewodzki Szpital Zakazny
city: Wroclaw
country: Poland
facility: EMC Instytut Medyczny SA
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: Vitoria-Gasteiz
country: Spain
facility: Hospital Txagorritxu
city: Bangkok
country: Thailand
facility: Chulalongkorn University Hospital
city: Khon Kaen
country: Thailand
facility: Khon Kaen University, Srinagarind Hospital
city: Nonthaburi
country: Thailand
facility: Bamrasnaradura Institute
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
state: Norfolk
city: Headington
country: United Kingdom
facility: Churchill Hospital
state: Oxford
city: Bradford
country: United Kingdom
facility: Bradford Teaching Hospitals NHS Foundation Trust
state: West Yorkshire
city: Leeds
country: United Kingdom
facility: St James's University Hospital
state: West Yorkshire
Study officials:
affiliation: University of Minnesota - Dept Biostatistics
name: James Neaton, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team; Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ, Gubareva LV, Xu X, Bridges CB, Uyeki TM. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med. 2009 Jun 18;360(25):2605-15. doi: 10.1056/NEJMoa0903810. Epub 2009 May 7.
citation: World Health Organization (WHO), www.who.int/, accessed 26 August 2013
citation: Guery B, Poissy J, el Mansouf L, Sejourne C, Ettahar N, Lemaire X, Vuotto F, Goffard A, Behillil S, Enouf V, Caro V, Mailles A, Che D, Manuguerra JC, Mathieu D, Fontanet A, van der Werf S; MERS-CoV study group. Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission. Lancet. 2013 Jun 29;381(9885):2265-72. doi: 10.1016/S0140-6736(13)60982-4. Epub 2013 May 30.
citation: Drosten C, Seilmaier M, Corman VM, Hartmann W, Scheible G, Sack S, Guggemos W, Kallies R, Muth D, Junglen S, Muller MA, Haas W, Guberina H, Rohnisch T, Schmid-Wendtner M, Aldabbagh S, Dittmer U, Gold H, Graf P, Bonin F, Rambaut A, Wendtner CM. Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection. Lancet Infect Dis. 2013 Sep;13(9):745-51. doi: 10.1016/S1473-3099(13)70154-3. Epub 2013 Jun 17.
citation: World Health Organization (WHO), Severe Acute Respiratory Syndrome (SARS), www.who.int/csr/sars/, accessed 26 August 2013
citation: Simonsen L, Higgs E, Taylor RJ, Wentworth D, Cozzi-Lepri A, Pett S, Dwyer DE, Davey R, Lynfield R, Losso M, Morales K, Glesby MJ, Weckx J, Carey D, Lane C, Lundgren J; INSIGHT FLU002 and FLU003 Study Groups. Using Clinical Research Networks to Assess Severity of an Emerging Influenza Pandemic. Clin Infect Dis. 2018 Jul 18;67(3):341-349. doi: 10.1093/cid/ciy088.
citation: Lynfield R, Davey R, Dwyer DE, Losso MH, Wentworth D, Cozzi-Lepri A, Herman-Lamin K, Cholewinska G, David D, Kuetter S, Ternesgen Z, Uyeki TM, Lane HC, Lundgren J, Neaton JD; INSIGHT Influenza Study Group. Outcomes of influenza A(H1N1)pdm09 virus infection: results from two international cohort studies. PLoS One. 2014 Jul 8;9(7):e101785. doi: 10.1371/journal.pone.0101785. eCollection 2014.