Respiratory Virus Hospitalization Study (FLU 003 Plus)

NCT ID: NCT01056185

Last Updated: 2024-10-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

1000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2009-08-31

Study Completion Date

2024-08-30

Brief Summary

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Following the sudden and unexpected emergence of influenza A(H1N1)pdm09 (2009 H1N1) virus, this observational study was initiated to estimate rates of morbidity and mortality and to examine predictors of severity among participants with 2009 H1N1 infection. 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. The current version of the protocol (released in August 2013) 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

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The purpose of this observational study is to describe the characteristics and outcomes over a 60-day follow-up period of participants with influenza virus infection (including influenza A subtypes such as H3N2 and 2009 H1N1, or influenza B), or a targeted non-influenza respiratory virus, who are hospitalized with severe illness and/or complications in geographically diverse locations.

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.

The information used from this study on participants with influenza and novel respiratory virus infections will be rapidly analyzed and shared broadly in order to guide policymakers and to design future studies.

Approximately 500 patients with influenza will be enrolled each year at an estimated 75 sites which are in geographically diverse locations across several continents.

Study Plan:

* Participants who meet the eligibility criteria will be enrolled at participating clinical sites.
* Patients with a diagnosis of influenza (confirmed or suspected), who are hospitalized with complications or severe disease, will be enrolled.
* 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 sample and lower respiratory tract sample, if appropriate. The respiratory specimens will be sent for central reverse transcriptase polymerase chain reaction (RT-PCR) testing for influenza.
* For participants who are still hospitalized, and not intubated, 5 to 7 days after enrollment an additional upper respiratory sample is obtained.
* Status will be re-assessed at approximately 28 days and 60 days after enrollment and another blood sample for serum and plasma will obtained at both time points.
* For participants who are mechanically ventilated additional upper and lower respiratory tract specimens will be obtained at specific timepoints.

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 of qualifying studies is 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 severe influenza.

Participating FLU 003 Plus sites are given the option to also participate in INSIGHT Genomics which requires a separate protocol registration. Participants, once consented to FLU 003 Plus, will be offered the option to also consent to INSIGHT Genomics which includes a single whole blood sample collection. Participation in FLU 003 Plus will not be compromised if a participant opts not to participate in INSIGHT Genomics.

Conditions

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Influenza Novel Respiratory Virus-1 Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) Novel Respiratory Virus-2 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Influenza

Influenza A and subtypes such as H3N2 and 2009 H1N1 or influenza B

No interventions assigned to this group

Novel Respiratory Virus-1

MERS-CoV (Middle East Respiratory Syndrome Coronavirus

No interventions assigned to this group

Novel Respiratory Virus-2

SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus)

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Be ≥ 18 years of age
* Have been admitted to hospital
* Have a signed informed consent by participant or surrogate/representative
* Have a local diagnosis (confirmed or suspected) of influenza, or of a targeted non-influenza viral respiratory infection\*, resulting in (or extending a previous) hospitalization

* A list of targeted non-influenza respiratory viruses is maintained on the INSIGHT website.

Exclusion Criteria

* Current imprisonment, or compulsory detention (involuntary incarceration) for treat of a psychiatric or physical illness.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

Clinical & Translational Science Institute, University of Minnesota

UNKNOWN

Sponsor Role collaborator

University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Cavan Reilly, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota - Dept Biostatistics

Locations

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UCSD Antiviral Research Center

San Diego, California, United States

Site Status

George Washington Medical Faculty Associates

Washington D.C., District of Columbia, United States

Site Status

Washington DC VA Medical Center

Washington D.C., District of Columbia, United States

Site Status

University of Illinois at Chicago

Chicago, Illinois, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Baystate Infectious Diseases Clinical Research

Springfield, Massachusetts, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Cooper University Hospital

Camden, New Jersey, United States

Site Status

New Jersey Medical School Adult Clinical Research Center

Newark, New Jersey, United States

Site Status

Cornell ID-CRU

New York, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

The Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

Miami Valley Hospital

Dayton, Ohio, United States

Site Status

University of Tennessee College of Medicine

Chattanooga, Tennessee, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Hospital Nacional Profesor Alejandro Posadas

El Palomar, Buenos Aires, Argentina

Site Status

Instituto Medico Platense

La Plata, Buenos Aires, Argentina

Site Status

Hospital Universitario Austral

Pilar, Buenos Aires, Argentina

Site Status

Hospital Profesor Bernardo Houssay

Vicente López, Buenos Aires, Argentina

Site Status

Sanatorio Britanico

Rosario, Santa Fe Province, Argentina

Site Status

CEMIC

Buenos Aires, , Argentina

Site Status

Hospital General de Agudos JM Ramos Mejia

Buenos Aires, , Argentina

Site Status

Hospital Interzonal General de Agudos Dr. Diego Paroissien

Buenos Aires, , Argentina

Site Status

Hospital Italiano de Buenos Aires

Buenos Aires, , Argentina

Site Status

Hospital Privado Centro Medico de Cordoba

Córdoba, , Argentina

Site Status

Hospital Rawson

Córdoba, , Argentina

Site Status

St. Vincent's Hospital

Darlinghurst, New South Wales, Australia

Site Status

Westmead Hospital

Westmead, New South Wales, Australia

Site Status

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Centre Hospitalier Universitaire St. Pierre (C.H.U. St. Pierre)

Brussels, , Belgium

Site Status

Clinica Alemana

Santiago, , Chile

Site Status

Fundacion Arriaran

Santiago, , Chile

Site Status

Arhus Universitetshospital, Skejby

Aarhus, , Denmark

Site Status

CHIP

Copenhagen, , Denmark

Site Status

Hvidovre University Hospital, Department of Infectious Diseases

Hvidovre, , Denmark

Site Status

Odense University Hospital

Odense, , Denmark

Site Status

Medizinische Universitatsklinik - Bonn, Immunologische Ambulanz CRS

Bonn, , Germany

Site Status

Klinik I fur Innere Medizin der Universitat zu Koln, Studienburo fur Infektiologie u. HIV

Cologne, , Germany

Site Status

Johann Wolfgang Goethe - University Hospital, Infektionsambulanz CRS

Frankfurt, , Germany

Site Status

1st Dept of Critical Care Medicine and Pulmonary Services, Evangelismos Hospital

Athens, , Greece

Site Status

1st Respiratory Medicine Dept, Athens Hosp for Diseases of the Chest "Sotiria Hospital"

Athens, , Greece

Site Status

Evangelismos General Hospital

Athens, , Greece

Site Status

Hippokration University General Hospital of Athens

Athens, , Greece

Site Status

Hospital Nacional Arzobispo Loayza

Lima, , Peru

Site Status

Hospital Nacional Guillermo Almenara Irigoyen

Lima, , Peru

Site Status

Hospital Clinico San Carlos

Madrid, , Spain

Site Status

Hospital La Paz

Madrid, , Spain

Site Status

Hospital Universitario Gregorio Mara�on

Madrid, , Spain

Site Status

Hospital Universitario Infanta Leonor

Madrid, , Spain

Site Status

Hospital Txagorritxu

Vitoria-Gasteiz, , Spain

Site Status

Chulalongkorn University Hospital

Bangkok, , Thailand

Site Status

Khon Kaen University, Srinagarind Hospital

Khon Kaen, , Thailand

Site Status

Bamrasnaradura Institute

Nonthaburi, , Thailand

Site Status

Heatherwood and Wexham Park Hospitals NHS Foundation Trust

Slough, Berkshire, United Kingdom

Site Status

Brighton and Sussex University Hospitals NHS Trust

Brighton, East Sussex, United Kingdom

Site Status

Churchill Hospital

Headington, Oxford, United Kingdom

Site Status

Sheffield Teaching Hospital NHS Foundation Trust

Sheffield, South Yorkshire, United Kingdom

Site Status

Bradford Teaching Hospitals NHS Foundation Trust

Bradford, West Yorkshire, United Kingdom

Site Status

St James's University Hospital

Leeds, West Yorkshire, United Kingdom

Site Status

Newcastle General Hospital

Newcastle upon Tyne, , United Kingdom

Site Status

Countries

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United States Argentina Australia Belgium Chile Denmark Germany Greece Peru Spain Thailand United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 19423869 (View on PubMed)

World Health Organization (WHO), www.who.int/, accessed 26 August 2013

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 23727167 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23782859 (View on PubMed)

World Health Organization (WHO), Severe Acute Respiratory Syndrome (SARS), www.who.int/csr/sars/, accessed 26 August 2013

Reference Type BACKGROUND

Wendt CH, Castro-Pearson S, Proper J, Pett S, Griffin TJ, Kan V, Carbone J, Koulouris N, Reilly C, Neaton JD; INSIGHT FLU003 Plus Study Group. Metabolite profiles associated with disease progression in influenza infection. PLoS One. 2021 Apr 2;16(4):e0247493. doi: 10.1371/journal.pone.0247493. eCollection 2021.

Reference Type DERIVED
PMID: 33798209 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29746631 (View on PubMed)

Pett SL, Kunisaki KM, Wentworth D, Griffin TJ, Kalomenidis I, Nahra R, Montejano Sanchez R, Hodgson SW, Ruxrungtham K, Dwyer D, Davey RT, Wendt CH; INSIGHT FLU003 Plus Study Group. Increased Indoleamine-2,3-Dioxygenase Activity Is Associated With Poor Clinical Outcome in Adults Hospitalized With Influenza in the INSIGHT FLU003Plus Study. Open Forum Infect Dis. 2017 Oct 25;5(1):ofx228. doi: 10.1093/ofid/ofx228. eCollection 2018 Jan.

Reference Type DERIVED
PMID: 29322062 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25004134 (View on PubMed)

Related Links

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Other Identifiers

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0603M83587 FLU 003

Identifier Type: -

Identifier Source: org_study_id

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