Evaluation of Efficacy and Safety of Peramivir in Adults With Acute Serious or Potentially Life-threatening Influenza
- Conditions
- Influenza
- Interventions
- Registration Number
- NCT00453999
- Lead Sponsor
- BioCryst Pharmaceuticals
- Brief Summary
This study has been designed as a randomized, double-blind, controlled, study to evaluate the efficacy and safety of two once daily intravenous peramivir regimens (200 mg and 400 mg) versus oral oseltamivir phosphate (75 mg twice daily) in hospitalized subjects with acute serious or potentially life threatening influenza. Study treatments will be provided for up to 5 consecutive days.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 137
- Age ≥18 years of age, male or female
- Able to provide informed consent, or for whom consent may be provided by guardian
- Presence of fever at time of screening of ≥38.0°C (≥ 100.0°F) taken orally, or ≥38.5°C (≥101.2°F) taken rectally. This requirement is waived if the subject has (1) a history of fever within 24 hours prior to screening and administered any antipyretic(s) in the 24 hours prior to screening, or (2) has no history of documented fever as defined above, but reports a symptom of feverishness at some time during 48 hours prior to screening
- Presence of at least 1 respiratory symptom (cough, sore throat, nasal congestion/symptoms) of any severity (mild, moderate, severe)
- Presence of at least 1 constitutional symptom (headache, myalgia, feverishness, malaise, fatigue) of any severity (mild, moderate, severe)
- Onset of illness no more than 72 hours before presentation. Time of onset of illness defined as either (1) the time when temperature (oral or rectal) was elevated (at least 1°C of elevation-oral temperature), OR (2) the time when the subject experienced the presence of at least 1 respiratory symptom AND the presence of at least 1 constitutional symptom
- Presence of 1 or more of the following factors in a subject willing to be hospitalized for inpatient observation and treatment:
- Age ≥60 years
- Presence of chronic obstructive pulmonary disease (COPD) or other chronic lung disease requiring daily pharmacotherapy
- History of congestive heart failure with or without medically significant recent change in cardiac status, but without signs or symptoms compatible with NYHA Class IV functional status
- 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
- Systolic blood pressure <90 mmHg
- Severity of illness that, in the Investigator's judgment, justifies hospitalization of the subject for supportive care
- Positive rapid antigen test (RAT) for influenza A and/or influenza B (using an approved test kit) or other test for influenza virus antigen performed in a clinical laboratory at the screening/enrollment evaluation
- Females of childbearing potential must report one of the following:
- Be surgically sterile or clinically post-menopausal
- Have been sexually abstinent 4 weeks prior to date of screening evaluation and be willing to remain abstinent through 4 weeks after study-drug administration for all perimenopausal women or women of child-bearing potential
- Use oral contraceptives or other form of hormonal birth control including hormonal vaginal rings or transdermal patches and have been using these for 3 months prior through 4 weeks after study-drug administration for all perimenopausal women or women of child-bearing potential
- Use an intra-uterine device (IUD), or adequate barrier contraception (or double-barrier method such as condom or diaphragm with spermicidal gel or foam) as birth control 4 weeks prior to date of screening evaluation through 4 weeks after study drug administration for all perimenopausal women or women of child-bearing potential
- Immunized against influenza with live attenuated virus vaccine in the previous weeks
- Treatment with any dose(s) of rimantadine, amantadine, zanamivir, or oseltamivir in the previous 7 days
- Current clinical evidence of a recognized or suspected acute non-influenzal infectious illness with onset prior to Screening
- Serum creatinine laboratory result at Screening >1.6 mg/dL or a result >25% above the upper limit of normal for the laboratory performing the test
- History of clinically significant proteinuria (≥1000 mg/24 hrs)
- History of moderate or severe renal impairment and/or previous clinical laboratory data indicating an estimated creatinine clearance <50 mL/min during the previous 12 months
- Electrocardiogram (ECG) at Screening visit showing evidence of acute ischemia, or presence of a medically significant dysrhythmia
- Presence of cardiac signs or symptoms compatible with NYHA Class III or Class IV functional status for congestive heart failure or angina (see NYHA Appendix V)
- Presence of diagnosed COPD or other chronic lung condition requiring either continuous or intermittent oxygen therapy as an outpatient. Note: Subjects who are determined to require acute supplemental oxygen therapy at the time of Screening and/or at hospital admission may be enrolled, if exclusion criteria #13 or #14 are not applicable.
- History of organ transplantation during the previous 12 months
- Known HIV infection with most recent CD4+ T-cell count ≤350 cells/mL
- History of diagnosis of any type of cancer (hematologic or solid tumor), that has required chemotherapy or radiation therapy in the previous 12 months, excluding non-melanomatous localized skin cancer
- Presence of ongoing requirement for chronic mechanical ventilation, either via oral or nasotracheal intubation or via tracheostomy, or chronic or intermittent requirement for BiPAP (bilevel positive airway pressure) at screening. Note: Subjects who require intermittent CPAP treatment for sleep apnea (without oxygen supplementation) may be enrolled
- Subjects who require acute mechanical ventilatory support of any type at the time of screening.
- History of alcohol abuse or drug addiction during the previous 12 months
- Participation in a clinical study of an experimental medication or other treatment during the previous 4 weeks
- Previous treatment with intravenous or intramuscular peramivir
- Women who are pregnant (positive serum or urine pregnancy test), who are attempting to become pregnant, or who are breast-feeding
- Subjects who have been hospitalized due to a condition other than acute influenza and in whom influenza is diagnosed during hospitalization.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: Peramivir 200 mg Peramivir 200 mg Peramivir 200 mg administered intravenously once daily for 5 days (5 doses) Arm 2: Peramivir 400 mg Peramivir 400 mg Peramivir 400 mg administered intravenously once daily for 5 days (5 doses) Arm 3: Oseltamivir Oseltamivir Oseltamivir 75 mg oral suspension administered orally twice daily for 5 days (10 doses)
- Primary Outcome Measures
Name Time Method Time to Clinical Stability (Kaplan-Meier Estimate) 14 days Time to clinical stability was summarized overall and for individual clinical signs for each treatment group using the method of Kaplan Meier. Subjects who did not experience clinical stability were censored at the date of their last non-missing assessment during the study (whether this assessment occurred as an inpatient or as an outpatient).
- Secondary Outcome Measures
Name Time Method Time to Resumption of Ability to Perform Usual Activities (Kaplan-Meier Estimate) 14 days Changes in each subject's ability to perform usual activities as determined from the visual analog scale (0 to 10, where 0 indicated subject was unable to perform usual activities at all and 10 indicated subject was able to perform all usual activities fully) were summarized by study visit and treatment group. The time to resumption of a subject's ability to perform usual activities was estimated using the method of Kaplan Meier. Subjects who did not return to the pre-study level of performance of usual activities were censored at the time of their last assessment. (Note: N is the number of ITTI participants with available data).
Change From Baseline in Scores of Symptoms of Influenza Baseline, Days 2, 3, 4, 5, 10, and 14 Descriptive statistics for the change from baseline in each of the 7 symptoms of influenza (cough; sore throat; nasal congestion; myalgia \[aches and pains\]; headache; feverishness; and fatigue, each graded on a 4-point severity scale \[0, absent; 1, mild; 2, moderate; 3, severe\]) were tabulated by treatment group. Missing data were excluded.
Time to Hospital Discharge (Kaplan-Meier Estimate) 14 days Time to discharge from hospital was estimated using the method of Kaplan Meier. Subjects who were not discharged from the hospital were censored at the time of their last assessment.
Incidence of Clinical Relapse of Influenza After Treatment (Number of Participants Experiencing Relapse During the Study) 14 days The number of subjects with clinical relapse, defined as changes in 2 or more signs of clinical stability to values outside the range of normalization criteria for a duration of at least 12 consecutive hours after clinical stability had been attained, were summarized by treatment group.
Change in Amount of Influenza Virus in Nose and Throat (Influenza A and B Combined) Baseline, and 12, 24, 36, 48, 72, and 96 hours Reduction in viral shedding, assessed as the change in quantitative viral titers and defined as the time-weighted change from baseline in TCID50/mL, was summarized for each treatment group.
Trial Locations
- Locations (83)
Pulmonary Associates of Mobile, P.C.
🇺🇸Mobile, Alabama, United States
Washington University School of Medicine
🇺🇸St. Louis, Missouri, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
Lowcountry Infectious Diseases, P.A.
🇺🇸Charleston, South Carolina, United States
Franciscan Health System
🇺🇸Tacoma, Washington, United States
Benmed / Pentagon Hospital
🇿🇦Benoni, Gauteng, South Africa
William Beaumont Hospital Troy
🇺🇸Troy, Michigan, United States
Mercury Street Medical Group, PLLC
🇺🇸Butte, Montana, United States
University of New Mexico
🇺🇸Albuquerque, New Mexico, United States
Jersey Shore University Medical Center
🇺🇸Neptune, New Jersey, United States
Rochester General Hospital/University of Rochester
🇺🇸Rochester, New York, United States
Hackensack University Medical Center, Department of Infectious Disease
🇺🇸Hackensack, New Jersey, United States
Veterans Affairs Medical Center
🇺🇸Salem, Virginia, United States
Centre de sante et de services sociaux Rimouski-Neigette (CSSSRN)
🇨🇦Rimouski, Quebec, Canada
Maisonneuve-Rosemont Hospital
🇨🇦Montreal, Quebec, Canada
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Marshfield Clinic
🇺🇸Marshfield, Wisconsin, United States
Prince Of Wales Hospital
🇦🇺Randwick, New South Wales, Australia
Westmead Hospital
🇦🇺Wentworthville, New South Wales, Australia
Mater Adult Hospital
🇦🇺South Brisbane, Queensland, Australia
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Medforum Hospital
🇿🇦Pretoria, Gauteng, South Africa
Eugene Marais Hospital
🇿🇦Pretoria, Gauteng, South Africa
Cairns Base Hospital
🇦🇺Cairns, Queensland, Australia
Waikato Hospital
🇳🇿Hamilton, New Zealand
Mount Sinai Hospital / Toronto Medical Laboratories
🇨🇦Toronto, Ontario, Canada
Global Clinical Trials (GCT)
🇿🇦Pretoria, Gauteng, South Africa
Tauranga Hospital
🇳🇿Tauranga, New Zealand
Dr. L.J. van Zyl
🇿🇦Worcester, W Cape, South Africa
Division of Infectious Diseases
🇨🇦Saskatoon, Saskatchewan, Canada
Newgate Centre
🇿🇦Johannesburg,, Gauteng, South Africa
The Prince of Wales Hospital
🇭🇰Shatin - New Territories, Hong Kong
Center de Sante et des Services Sociaux de Chicoutimi
🇨🇦Chicoutimi, Quebec, Canada
Centre Hospitalier Universitaire de Quebec-Pavillon CHUL
🇨🇦Quebec, Canada
Sebastian, P
🇿🇦Durban, KZ-Natal, South Africa
Eksteen, MC
🇿🇦Nelspruit, Mpumalanga, South Africa
N1 City Hospital
🇿🇦Cape town, WC, South Africa
Private Practice
🇿🇦Cape Town, Gauteng, South Africa
Infectious Disease of Indiana, PSC
🇺🇸Indianapolis, Indiana, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Wayne State University School of Medicine
🇺🇸Detroit, Michigan, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
University of Utah Health Sciences Center
🇺🇸Salt Lake City, Utah, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
The Ottawa Hospital - General Campus
🇨🇦Ottawa, Ontario, Canada
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Kelowna General Hospital
🇨🇦Kelowna, British Columbia, Canada
National University Hospital
🇸🇬Singapore, Singapore
Tan Tock Seng Hospital
🇸🇬Singapore, Singapore
Genclin Corporation
🇿🇦Bloemfontein, Free State, South Africa
St. Bernards Research Center/Clopton Clinic
🇺🇸Jonesboro, Arkansas, United States
Pulmonary Consultants & Primary Care Physicians Medical Group, Inc.
🇺🇸Orange, California, United States
University of California Irvine Medical Center
🇺🇸Orange, California, United States
Good Samaritan Hospital
🇺🇸San Jose, California, United States
National Jewish Medical and Research Center, Clinical Research Unit
🇺🇸Denver, Colorado, United States
Orlando Regional Healthcare
🇺🇸Orlando, Florida, United States
Medical College of Georgia
🇺🇸Augusta, Georgia, United States
Infectious Disease Specialists of Atlanta, P.C.
🇺🇸Decatur, Georgia, United States
St. Joseph's/Candler Health System, Inc.
🇺🇸Savannah, Georgia, United States
Idaho Falls Infectious Diseases, PLLC
🇺🇸Idaho Falls, Idaho, United States
Springfield Clinic, LLP
🇺🇸Springfield, Illinois, United States
Wishard Hospital/Indiana University
🇺🇸Indianapolis, Indiana, United States
Natchitoches Internal Medicine
🇺🇸Natchitoches, Louisiana, United States
Louisiana State University Health Sciences Center-Shreveport
🇺🇸Shreveport, Louisiana, United States
VA Maryland Health Care System
🇺🇸Baltimore, Maryland, United States
Franklin Square Hospital
🇺🇸Baltimore, Maryland, United States
Gold Coast Hospital
🇦🇺Southport, Queensland, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
James A. Haley Veterans Hospital, Department of Infectious Disease
🇺🇸Tampa, Florida, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Repatriation General Hospital
🇦🇺Daw Park, South Australia, Australia
University of California Davis Medical Center, Department of Emergency Medicine
🇺🇸Sacramento, California, United States
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Global Clinical Trial Center
🇿🇦Port Elizabeth, E. Cape, South Africa
DJW Navorsing
🇿🇦Krugersdorp, Gauteng, South Africa
Dr Bhorat
🇿🇦Soweto, Gauteng, South Africa
Hamilton Health Sciences-McMaster University Medical Centre
🇨🇦Hamilton, Ontario, Canada
St. Joseph's Healthcare Hamilton-L424
🇨🇦Hamilton, Ontario, Canada
United Christian Hospital
🇭🇰Hong Kong, Hong Kong
Princess Margaret Hospital
🇭🇰Hong Kong, Hong Kong