Clinical trial NCT00958776: A Study to Evaluate the Efficacy and Safety of IV Peramivir in Addition to Standard of Care Compared to Standard of Care Alone in Adults and Adolescents Who Are Hospitalized Due to Influenza
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Controlled Study to Evaluate the Efficacy and Safety of Peramivir Administered Intravenously in Addition to Standard of Care Compared to Standard of Care Alone in Adults and Adolescents Who Are Hospitalized Due to Serious Influenza
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Cough
Sore Throat
Nasal Congestion
Headache
Fever
Seasonal Influenza
Keywords: Influenza
Hospitalized
Antiviral
Flu
Lead sponsor: BioCryst Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Department of Health and Human Services
First posted: 2009-08-13
Enrollment: 405
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Phase 3, multicenter, randomized, double-blind, controlled study to evaluate the efficacy and safety of peramivir administered intravenously in addition to standard of care compared to standard of care alone in adults and adolescents who are hospitalized due to serious influenza.


Eligibility criteria: Inclusion Criteria:

* Age ≥12 years of age, male or female.
* Able to provide informed consent, or for whom consent may be provided by guardian, unless informed consent provided by a guardian or a legally authorized representative is not consistent with applicable local or ethical concerns, procedures, directives and/or guidelines.
* Subject must have at least one of the following clinical presentations at Screening:

  1. Oral temperature ≥ 38.0 °C (≥100.4 °F), ≥38.6°C (≥101.4 °F) tympanic or rectal OR
  2. Oxygen saturation \<92%, OR
  3. Two out of the following three vital signs:

Respiration rate \>24/minute, Heart rate \>100/minute, Systolic BP \<90 mmHg

* Presence of at least one respiratory symptom (cough, sore throat, or nasal congestion) of any severity (mild, moderate, or severe).
* Presence of at least one constitutional symptom (headache, myalgia, feverishness, or fatigue) of any severity (mild, moderate, or severe).
* Onset of illness no more than 72 hours before presentation. Note: Time of onset of illness is defined as the earlier of either (1) the time when the temperature was first measured as elevated, OR (2) the time when the subject experienced the presence of at least one respiratory symptom AND the presence of at least one constitutional symptom.
* Either:

Severity of illness that, in the Investigator's judgment, justifies hospitalization of the subject for supportive care.

OR

Presence of one or more of the following factors:

Age ≥60 years. Presence of chronic obstructive pulmonary disease (COPD) or other chronic lung disease requiring daily pharmacotherapy.

Current history of congestive heart failure or angina. Presence of diabetes mellitus, clinically stable or unstable. Transcutaneous oxygen saturation \<94% without supplemental oxygen for at least 5 minutes, or a medically significant decrease in oxygen saturation from an established baseline value (an investigative site at altitude \>2000 ft above sea level will utilize different criteria for oxygen saturation).

History of chronic renal impairment not requiring peritoneal dialysis. Serum creatinine \> 2.0 mg/dL or \> 177 μmol/L.

* Diagnosis of Influenza by satisfying one of the following:

  1. Clinical Influenza with Positive Diagnostic Test. Subjects who have a positive rapid antigen test (RAT) for influenza A and/or influenza B (using a Sponsor-approved test kit), or positive test (using other methodology) for influenza A and/or B virus antigen or RNA performed in a clinical laboratory at the screening/enrollment evaluation are eligible for enrollment.

     OR
  2. Clinical Influenza with Negative Rapid Antigen Test (RAT). Subjects with a negative RAT test may be enrolled once the site has been approved by the Sponsor to enroll such subjects, based on documentation of an outbreak of influenza in the community. An influenza outbreak may be documented in the catchment area of the hospital via one of the following methods: 1) local confirmation of influenza A or B infection in the current influenza season by a) the institution's local laboratory, or b) the local public health system, or c) the national public health system, or d) a laboratory of a recognized multinational influenza surveillance scheme such as the European Influenza Surveillance Network (EISN); 2) prior enrollment of a RAT positive subject into this study at the same institution in the current influenza season.

     Exclusion Criteria:
* Subjects who have been hospitalized for greater than 24 hours (not including time spent in the Emergency Department).
* Treatment with any dose(s) of rimantadine, amantadine, ribavirin, zanamivir, or oseltamivir in the previous 7 days.
* Blood platelet count of \< 20 x 109/L at the time of the screening evaluation.
* Serum bilirubin \> 6 mg/dL or \> 105 μmol/L at time of screening evaluation.
* Serum ALT or AST \> 5 times the upper limit of normal at time of screening evaluation.
* Congestive heart failure of NYHA Class III or Class IV functional status.
* Serum creatinine \> 5.0 mg/dL or \> 500 μmol/L at time of screening evaluation.
* Subjects who require peritoneal dialysis.
* Altered neurologic status as defined by a Glasgow Coma Score of ≤ 9, unless medically induced.
* Females who are pregnant (positive urine or serum pregnancy test at screening evaluation) or breastfeeding.
* Actively undergoing systemic chemotherapy or radiotherapy treatment for a malignancy. Subjects who have completed treatment 30 days prior to enrollment are not excluded. Hormone treatment for cancer is also not excluded.
* Prior hematopoietic stem cell transplantation or solid organ transplant during the previous 4 months.
* HIV infection with a known CD4 count \< 200 cells/mm3 unless on a stable highly active antiretroviral therapy (HAART) for at least 6 months.
* Presence of a pre-existing chronic infection that is undergoing or requiring medical therapy (eg, tuberculosis). Subjects with chronic osteomyelitis or Hepatitis B or C not requiring treatment are not excluded.
* Presence of any pre-existing illness that, in the opinion of the investigator, would place the subject at an unreasonably increased risk through participation in this study.
* Previous treatment with intravenous or intramuscular peramivir.
* Participation as a subject in any study of an experimental treatment for any condition within the 30 days prior to the time of the screening evaluation.
* Subjects diagnosed with Cystic Fibrosis.
* Subjects with confirmed clinical evidence of acute non-influenzal infection at the time of screening evaluation.
* Subjects who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol.

Primary outcomes:
measure: Time to Clinical Resolution (Kaplan-Meier Estimate)
timeFrame: 10 days
Secondary outcomes:
measure: Change (Reduction) in Influenza Virus Titer
timeFrame: Baseline and 24, 48, 108 hours
measure: Time to Alleviation of Clinical Symptoms of Influenza
timeFrame: 10 days
measure: Time to Resolution of Fever (Kaplan-Meier Estimate)
timeFrame: 10 days
measure: Time to Resumption of Usual Activities
timeFrame: 10 days
measure: Number of Subjects With ICU Admission
timeFrame: 10 days
measure: Duration of All ICU Admissions (Kaplan-Meier Estimate)
timeFrame: 10 days
Other outcomes:
measure: Time to Hospital Discharge
timeFrame: 10 days
measure: Incidence of Influenza-Related Complications
timeFrame: 10 days
measure: Number of Subjects Requiring More Than 5 Days of Study Drug
timeFrame: 10 days
measure: Survival at 14 and 28 Days After Initiation of Study Drug (Kaplan-Meier Estimate)
timeFrame: 28 days
measure: Initial Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; IC50 (nM)
timeFrame: Initial (baseline or post-baseline) and up to 10 days
measure: Change in Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; Fold Change From Initial
timeFrame: Initial (baseline or post-baseline) and up to 10 days
Locations:
city: La Mesa
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Modesto
country: United States
state: California
city: Oceanside
country: United States
state: California
city: Orange
country: United States
facility: Pulmonary Consultants PC Physicians Medical Group, Inc.
state: California
city: Orange
country: United States
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Diego
country: United States
facility: Sharp Chula Vista Medical Center
state: California
city: San Diego
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Wheat Ridge
country: United States
facility: Drogue Medical, LLC
state: Colorado
city: Washington
country: United States
facility: Washington Hospital Center CAR
state: District of Columbia
city: Washington
country: United States
state: District of Columbia
city: Ft. Lauderdale
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Winter Park
country: United States
facility: Florida Hospital
state: Florida
city: Columbus
country: United States
state: Georgia
city: Decatur
country: United States
facility: DeKalb Medical Center
state: Georgia
city: Savannah
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Moline
country: United States
facility: Medical Arts Associates, Ltd.
state: Illinois
city: Springfield
country: United States
state: Illinois
city: South Bend
country: United States
state: Indiana
city: Hazard
country: United States
facility: Kentucky Lung Clinic
state: Kentucky
city: Natchitoches
country: United States
state: Louisiana
city: New Orleans
country: United States
state: Louisiana
city: Annapolis
country: United States
state: Maryland
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University - Hutzel Hospital
state: Michigan
city: Detroit
country: United States
facility: Wayne State University, Department of Emergency Medicine
state: Michigan
city: Detroit
country: United States
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Troy
country: United States
facility: William Beaumont Hospital
state: Michigan
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: St. Louis
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: New Brunswick
country: United States
state: New Jersey
city: Bronx
country: United States
state: New York
city: Manhasset
country: United States
state: New York
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill AIDS Clinical Trials Unit
state: North Carolina
city: Columbus
country: United States
facility: Remington-Davis, Inc.
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Kettering
country: United States
state: Ohio
city: Lima
country: United States
facility: Regional Infection Diseases Infusion Center Inc.
state: Ohio
city: Toledo
country: United States
facility: ID Clinical Research, LTD
state: Ohio
city: Toledo
country: United States
facility: Medical College Of Ohio
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Allentown
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: East Providence
country: United States
state: Rhode Island
city: Charleston
country: United States
state: South Carolina
city: Sioux Falls
country: United States
state: South Dakota
city: San Antonio
country: United States
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Roanoke
country: United States
facility: Carilion Infectious Disease
state: Virginia
city: Salem
country: United States
facility: VA Medical Center - Salem
state: Virginia
city: Buenos Aires
country: Argentina
facility: Hospital del Torax Dr. Antonio A. Cetrangolo
city: Buenos Aires
country: Argentina
city: Caba
country: Argentina
city: Cordoba
country: Argentina
city: Mendoza
country: Argentina
city: Merlo
country: Argentina
city: Rosario
country: Argentina
city: Santa Fe
country: Argentina
city: Vicente Lopez
country: Argentina
city: Bruxelles
country: Belgium
city: Liege
country: Belgium
city: Mons
country: Belgium
city: Sarajevo
country: Bosnia and Herzegovina
city: Tuzla
country: Bosnia and Herzegovina
city: Belo Horizonte
country: Brazil
state: MG
city: Curitiba
country: Brazil
state: PR
city: Passo Fundo
country: Brazil
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: RS
city: Porto Alegre
country: Brazil
state: RS
city: Campinas
country: Brazil
state: SP
city: Santo Andre
country: Brazil
state: SP
city: Santos
country: Brazil
state: SP
city: Sao Paulo
country: Brazil
state: SP
city: Plovdiv
country: Bulgaria
city: Ruse
country: Bulgaria
facility: DDPPDI - Ruse
city: Sofia
country: Bulgaria
facility: Fifth MHAT-Sofia, AD
city: Sofia
country: Bulgaria
facility: MHAT - Tokuda Hospital Sofia, AD
city: Sofia
country: Bulgaria
facility: Military Medical Academy - MHAT
city: Sofia
country: Bulgaria
city: Stara Zagora
country: Bulgaria
facility: MHAT - Tokuda Hospital Sofia, AD
city: Veliko Tarnovo
country: Bulgaria
facility: MHAT 'Dr. St. Cherkezov', AD
city: Kelowna
country: Canada
state: British Columbia
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Kingston
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Chicoutimi
country: Canada
state: Quebec
city: Sherbrooke
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Concepcion
country: Chile
facility: Hospital Clinico Regional Dr. Guillermo Grant Benavente
city: Santiago
country: Chile
facility: Hosp. de Urgencia Asistencia Publica Dr. Alejandro del Rio
city: Santiago
country: Chile
city: Temuco
country: Chile
city: Brno
country: Czech Republic
facility: Fakultni nemocnice Brno
city: Hradec Kralove
country: Czech Republic
city: Praha
country: Czech Republic
city: Tabor
country: Czech Republic
city: Usti nad Labem
country: Czech Republic
facility: Krajska zdravotni, a.s. - Masarykova nemocnice v Ustinad La
city: Berlin
country: Germany
city: Erlangen
country: Germany
city: Goettingen
country: Germany
city: Koeln
country: Germany
city: Mainz
country: Germany
city: Regensburg
country: Germany
facility: Universitaetsklinikum Regensburg
city: Debrecen
country: Hungary
city: Fehergyarmat
country: Hungary
city: Szekesfehervar
country: Hungary
facility: Fejer Megyei Szent Gyorgy Korhaz
city: Szentes
country: Hungary
facility: Principal SMO Dr. Bugyi Istvan Korhaz Szentes
city: Zalaegerszeg
country: Hungary
city: Hyderabad
country: India
state: Andhra Pradesh
city: Secunderabad
country: India
state: Andhra Pradesh
city: Ahmedabad
country: India
state: Gujarat
city: Karamsad
country: India
state: Gujarat
city: Surat
country: India
state: Gujarat
city: Vadodara
country: India
state: Gujarat
city: Faridabad
country: India
state: Haryana
city: Srinagar
country: India
state: Jammu & Kashmir
city: Bangalore
country: India
state: Karnataka
city: Mangalore
country: India
state: Karnataka
city: Ernakulam
country: India
state: Kerala
city: Thrissur
country: India
state: Kerala
city: Trivandrum
country: India
state: Kerala
city: Cherthala
country: India
state: Maharashtra
city: Mumbai
country: India
state: Maharashtra
city: Nagpur
country: India
state: Maharashtra
city: Nashik
country: India
state: Maharashtra
city: Pune
country: India
state: Maharashtra
city: Mohali
country: India
state: Punjab
city: Bikaner
country: India
state: Rajasthan
city: Jaipur
country: India
facility: Fortis Escort Hospital
state: Rajasthan
city: Chennai
country: India
facility: Apollo First Med Hospitals
state: Tamil Nadu
city: Chennai
country: India
facility: Life Line Multispecialty Hospital
state: Tamil Nadu
city: Chennai
country: India
state: Tamil Nadu
city: Coimbatore
country: India
state: Tamil Nadu
city: Lucknow
country: India
state: Uttar Pradesh
city: Kolkata
country: India
state: West Bengal
city: Delhi
country: India
city: Afula
country: Israel
city: Haifa
country: Israel
city: Holon
country: Israel
city: Jerusalem
country: Israel
city: Kfar Saba
country: Israel
city: Ramat Gan
country: Israel
city: Tel Aviv
country: Israel
city: Liepaja
country: Latvia
city: Rezekne
country: Latvia
city: Valmiera
country: Latvia
city: Ventspils
country: Latvia
city: Beirut
country: Lebanon
city: Arequipa
country: Peru
city: Cuzco
country: Peru
city: Lima
country: Peru
city: Bydgoszcz
country: Poland
city: Lancut
country: Poland
city: Lodz
country: Poland
city: Mielec
country: Poland
city: Poznan
country: Poland
city: Pulawy
country: Poland
city: Engels
country: Russian Federation
city: Niznhy Novgorod
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Tomsk
country: Russian Federation
city: Belgrade
country: Serbia
city: Kragujevac
country: Serbia
city: Nis
country: Serbia
city: Novi Sad
country: Serbia
city: Trnava
country: Slovakia
city: Middelburg
country: South Africa
state: Mpumalanga
city: Bloemfontein
country: South Africa
city: Dundee
country: South Africa
city: Durban
country: South Africa
city: Krugersdorp
country: South Africa
city: Limpopo
country: South Africa
city: Port Elizabeth
country: South Africa
city: Pretoria
country: South Africa
city: Somerset West
country: South Africa
city: Worcester
country: South Africa
city: Chernivci
country: Ukraine
city: Donetsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Odesa
country: Ukraine
city: Poltava
country: Ukraine
city: Sumy
country: Ukraine
city: Vinnytsya
country: Ukraine
city: Leicester
country: United Kingdom
Study officials:
References:
citation: de Jong MD, Ison MG, Monto AS, Metev H, Clark C, O'Neil B, Elder J, McCullough A, Collis P, Sheridan WP. Evaluation of intravenous peramivir for treatment of influenza in hospitalized patients. Clin Infect Dis. 2014 Dec 15;59(12):e172-85. doi: 10.1093/cid/ciu632. Epub 2014 Aug 12.