Respiratory Virus Hospitalization Study (FLU 003 Plus)

Influenza Clinical Trial

Official title:

An International Observational Study to Characterize Adults Who Are Hospitalized With Influenza or Other Targeted Respiratory Viruses

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01056185
• Other study ID #: 0603M83587 FLU 003
• Status: Recruiting
• Start date: August 2009
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: University of Minnesota
• Contact: Eileen Denning, MPH
• Phone: 612-626-8049
• Email: edenning[@]umn.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Coronavirus Infections
• Influenza
• Influenza, Human
• Novel Respiratory Virus-1 Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV)
• Novel Respiratory Virus-2 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)
• Severe Acute Respiratory Syndrome
• Syndrome
• Virus Diseases

Locations

Country	Name	City	State
Argentina	CEMIC	Buenos Aires
Argentina	Hospital General de Agudos JM Ramos Mejia	Buenos Aires
Argentina	Hospital Interzonal General de Agudos Dr. Diego Paroissien	Buenos Aires
Argentina	Hospital Italiano de Buenos Aires	Buenos Aires
Argentina	Hospital Privado Centro Medico de Cordoba	Cordoba
Argentina	Hospital Rawson	Cordoba
Argentina	Hospital Nacional Profesor Alejandro Posadas	El Palomar	Buenos Aires
Argentina	Instituto Medico Platense	La Plata	Buenos Aires
Argentina	Hospital Universitario Austral	Pilar	Buenos Aires
Argentina	Sanatorio Britanico	Rosario	Santa Fe
Argentina	Hospital Profesor Bernardo Houssay	Vicente Lopez	Buenos Aires
Australia	St. Vincent's Hospital	Darlinghurst	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Westmead Hospital	Westmead	New South Wales
Belgium	Centre Hospitalier Universitaire St. Pierre (C.H.U. St. Pierre)	Brussels
Chile	Clinica Alemana	Santiago
Chile	Fundacion Arriaran	Santiago
Denmark	Arhus Universitetshospital, Skejby	Aarhus
Denmark	CHIP	Copenhagen
Denmark	Hvidovre University Hospital, Department of Infectious Diseases	Hvidovre
Denmark	Odense University Hospital	Odense
Germany	Medizinische Universitatsklinik - Bonn, Immunologische Ambulanz CRS	Bonn
Germany	Klinik I fur Innere Medizin der Universitat zu Koln, Studienburo fur Infektiologie u. HIV	Cologne
Germany	Johann Wolfgang Goethe - University Hospital, Infektionsambulanz CRS	Frankfurt
Greece	1st Dept of Critical Care Medicine and Pulmonary Services, Evangelismos Hospital	Athens
Greece	1st Respiratory Medicine Dept, Athens Hosp for Diseases of the Chest "Sotiria Hospital"	Athens
Greece	Evangelismos General Hospital	Athens
Greece	Hippokration University General Hospital of Athens	Athens
Peru	Hospital Nacional Arzobispo Loayza	Lima
Peru	Hospital Nacional Guillermo Almenara Irigoyen	Lima
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital La Paz	Madrid
Spain	Hospital Universitario Gregorio Mara?on	Madrid
Spain	Hospital Universitario Infanta Leonor	Madrid
Spain	Hospital Txagorritxu	Vitoria-Gasteiz
Thailand	Chulalongkorn University Hospital	Bangkok
Thailand	Khon Kaen University, Srinagarind Hospital	Khon Kaen
Thailand	Bamrasnaradura Institute	Nonthaburi
United Kingdom	Bradford Teaching Hospitals NHS Foundation Trust	Bradford	West Yorkshire
United Kingdom	Brighton and Sussex University Hospitals NHS Trust	Brighton	East Sussex
United Kingdom	Churchill Hospital	Headington	Oxford
United Kingdom	St James's University Hospital	Leeds	West Yorkshire
United Kingdom	Newcastle General Hospital	Newcastle upon Tyne
United Kingdom	Sheffield Teaching Hospital NHS Foundation Trust	Sheffield	South Yorkshire
United Kingdom	Heatherwood and Wexham Park Hospitals NHS Foundation Trust	Slough	Berkshire
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Cooper University Hospital	Camden	New Jersey
United States	University of Tennessee College of Medicine	Chattanooga	Tennessee
United States	University of Illinois at Chicago	Chicago	Illinois
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Cornell ID-CRU	New York	New York
United States	New Jersey Medical School Adult Clinical Research Center	Newark	New Jersey
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	UCSD Antiviral Research Center	San Diego	California
United States	Baystate Infectious Diseases Clinical Research	Springfield	Massachusetts
United States	George Washington Medical Faculty Associates	Washington	District of Columbia
United States	Washington DC VA Medical Center	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
University of Minnesota	National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)

Countries where clinical trial is conducted

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

References & Publications (5)

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. — View 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. Erratum In: Lancet. 2013 Jun 29;381(9885):2254. — View 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. Erratum In: N Engl J Med. 2009 Jul 2;361(1):102. — View Citation

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

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death		60-day period following enrollment
Secondary	Recovery from influenza illness (including days lost from normal activities) duration of hospitalization, days in intensive care, days of mechanical ventilation, days of dialysis, pregnancy outcome		approximately 60 days

External Links

•   INSIGHT website