Respiratory Virus Hospitalization Study (FLU 003 Plus)

Completed

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

• Registration Number: NCT01056185
• Lead Sponsor: University of Minnesota

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2009-08
• Study First Submitted: 2010-01-25
• Study First Submitted QC: 2010-01-25
• Study First Posted: 2010-01-26
• Primary Completion: 2024-08-30
• Study Completion: 2024-08-30
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-17
• Last Update Posted: 2024-10-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1000

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Death	60-day period following enrollment

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (63)

Hospital Nacional Arzobispo Loayza; 🇵🇪 Lima, Peru

Hospital Nacional Guillermo Almenara Irigoyen; 🇵🇪 Lima, Peru

UCSD Antiviral Research Center; 🇺🇸 San Diego, California, United States

George Washington Medical Faculty Associates; 🇺🇸 Washington, District of Columbia, United States

Washington DC VA Medical Center; 🇺🇸 Washington, District of Columbia, United States

University of Illinois at Chicago; 🇺🇸 Chicago, Illinois, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Baystate Infectious Diseases Clinical Research; 🇺🇸 Springfield, Massachusetts, United States

Hospital Clinico San Carlos; 🇪🇸 Madrid, Spain

Henry Ford Health System; 🇺🇸 Detroit, Michigan, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Cooper University Hospital; 🇺🇸 Camden, New Jersey, United States

New Jersey Medical School Adult Clinical Research Center; 🇺🇸 Newark, New Jersey, United States

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States

Cornell ID-CRU; 🇺🇸 New York, New York, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

The Ohio State University Medical Center; 🇺🇸 Columbus, Ohio, United States

Miami Valley Hospital; 🇺🇸 Dayton, Ohio, United States

University of Tennessee College of Medicine; 🇺🇸 Chattanooga, Tennessee, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Hospital La Paz; 🇪🇸 Madrid, Spain

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

Hospital Profesor Bernardo Houssay; 🇦🇷 Vicente Lopez, Buenos Aires, Argentina

Sanatorio Britanico; 🇦🇷 Rosario, Santa Fe, 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 Universitario Gregorio Mara�on; 🇪🇸 Madrid, Spain

Hospital Privado Centro Medico de Cordoba; 🇦🇷 Cordoba, Argentina

Hospital Rawson; 🇦🇷 Cordoba, Argentina

St. Vincent's Hospital; 🇦🇺 Darlinghurst, New South Wales, Australia

Westmead Hospital; 🇦🇺 Westmead, New South Wales, Australia

The Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia

Centre Hospitalier Universitaire St. Pierre (C.H.U. St. Pierre); 🇧🇪 Brussels, Belgium

Clinica Alemana; 🇨🇱 Santiago, Chile

Fundacion Arriaran; 🇨🇱 Santiago, Chile

Arhus Universitetshospital, Skejby; 🇩🇰 Aarhus, Denmark

CHIP; 🇩🇰 Copenhagen, Denmark

Hvidovre University Hospital, Department of Infectious Diseases; 🇩🇰 Hvidovre, Denmark

Odense University Hospital; 🇩🇰 Odense, Denmark

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, Germany

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, Greece

Hospital Universitario Infanta Leonor; 🇪🇸 Madrid, Spain

Hospital Txagorritxu; 🇪🇸 Vitoria-Gasteiz, Spain

Chulalongkorn University Hospital; 🇹🇭 Bangkok, Thailand

Khon Kaen University, Srinagarind Hospital; 🇹🇭 Khon Kaen, Thailand

Bamrasnaradura Institute; 🇹🇭 Nonthaburi, Thailand

Heatherwood and Wexham Park Hospitals NHS Foundation Trust; 🇬🇧 Slough, Berkshire, United Kingdom

Brighton and Sussex University Hospitals NHS Trust; 🇬🇧 Brighton, East Sussex, United Kingdom

Churchill Hospital; 🇬🇧 Headington, Oxford, United Kingdom

Sheffield Teaching Hospital NHS Foundation Trust; 🇬🇧 Sheffield, South Yorkshire, United Kingdom

Bradford Teaching Hospitals NHS Foundation Trust; 🇬🇧 Bradford, West Yorkshire, United Kingdom

St James's University Hospital; 🇬🇧 Leeds, West Yorkshire, United Kingdom

Newcastle General Hospital; 🇬🇧 Newcastle upon Tyne, United Kingdom