Comparing the Efficacy, Safety, and Tolerability of Combination Antivirals (Amantadine, Ribavirin, Oseltamivir) Versus Oseltamivir for the Treatment of Influenza in Adults at Risk for Complications
IRC003
A Randomized Double-Blind Phase 2 Study Comparing the Efficacy, Safety, and Tolerability of Combination Antivirals (Amantadine, Ribavirin, Oseltamivir) Versus Oseltamivir for the Treatment of Influenza in Adults at Risk for Complications
2 other identifiers
interventional
881
5 countries
91
Brief Summary
Seasonal influenza is responsible for many hospitalizations and deaths each year, despite effective antiviral treatments. Some individuals have medical conditions such as heart or lung diseases that make them particularly at risk of severe influenza infections that may result in hospitalization or death. Oseltamivir (Tamiflu) is used most often to treat flu, but there are still many hospitalizations, complications, and deaths even with treatment. This study evaluated the use of combination antivirals (amantadine, oseltamivir, and ribavirin) compared to oseltamivir alone in the treatment of influenza in an at-risk population.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Sep 2010
Longer than P75 for phase_2
91 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2010
CompletedFirst Submitted
Initial submission to the registry
October 22, 2010
CompletedFirst Posted
Study publicly available on registry
October 25, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 2, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
March 30, 2017
CompletedResults Posted
Study results publicly available
July 11, 2017
CompletedFebruary 4, 2019
January 1, 2019
5.7 years
October 22, 2010
May 31, 2017
January 31, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With Virus Detectable by Quantitative PCR (qPCR) in Nasopharyngeal (NP) Swabs
The central laboratory performed a qualitative PCR test on the NP sample from Day 0 in order to confirm influenza infection and to determine the influenza type and subtype. For participants with a positive influenza test result at Day 0 from this qualitative PCR testing, the laboratory then performed qPCR testing of subsequent samples to quantify viral shedding.
At Day 3
Secondary Outcomes (14)
Number of Participants by Virus Detection Status
At Day 0, 3 and 7.
qPCR Viral Shedding
At Day 0, 3 and 7
Number of Participants Shedding Virus
At day 3 and 7.
Time to Alleviation of Influenza Clinical Symptoms.
From treatment initiation to Day 28
Time to Absence of Fever
From treatment initiation to Day 28
- +9 more secondary outcomes
Study Arms (2)
Combination Therapy
EXPERIMENTALAmantadine, Ribavirin, Oseltamivir
Oseltamivir monotherapy
ACTIVE COMPARATOROseltamivir
Interventions
Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.
Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.
Eligibility Criteria
You may qualify if:
- Enrollment (Screening)
- Signed informed consent prior to initiation of any study procedures
- Presence of an underlying medical condition(s) that might increase risk of complications from influenza
- History of an influenza-like illness defined as:
- One or more respiratory symptom (cough, sore throat, or nasal symptoms) AND
- Either
- Fever (subjective or documented \>38 degrees C) OR
- or more constitutional symptom (headache, malaise, myalgia, sweats/chills or fatigue)
- Onset of illness no more than 96 hours before screening defined as when the subject experienced at least one respiratory symptom, constitutional symptom, or fever
- Willingness to have samples stored
- Randomization
- Signed informed consent
- Presence of a medical condition(s) that had been associated with increased risk of complications from influenza
- Age 65 years of age or older
- Asthma
- +2 more criteria
You may not qualify if:
- Endocrine disorders (such as diabetes mellitus)
- Kidney disorders
- Liver disorders
- Metabolic disorders (such as inherited metabolic disorders and mitochondrial disorders)
- Weakened immune system due to disease or medication (such as people with HIV/AIDS, or cancer, chronic steroids or other medications causing immune suppression)
- BMI ≥ 40(kg/m²)
- Onset of illness no more than 96 hours before screening defined as when the subject experienced at least one respiratory symptom, constitutional symptom, or fever
- Positive test for influenza (either rapid antigen or PCR)
- \- Results from influenza testing obtained for clinical indications within 12 hours before screening/enrollment may be used if available. Randomization may proceed in cases of discrepant results (one positive and one negative)
- One of the following to avoid pregnancy:
- Females who were able to become pregnant (i.e., are not postmenopausal, have not undergone surgical sterilization, and are sexually active with men) must agree to use at least 2 effective forms of contraception from the date of informed consent through 6 months after the last dose of study drug. At least one of the methods of contraception should be a barrier method
- Males who had not undergone surgical sterilization and are sexually active with women must agree to use condoms plus have a partner use at least one additional effective form of contraception from the date of informed consent through 6 months after the last dose of study drug
- Willingness to have samples stored
- (for Enrollment or Randomization)
- Women who were pregnant or breast-feeding, and men whose female partner(s) was pregnant
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (91)
Simon Williamson Clinic
Birmingham, Alabama, 35211, United States
East Valley Family Physicians
Chandler, Arizona, 85224, United States
Thomas Lenzmeier Family Practice
Glendale, Arizona, 85308, United States
Central Phoenix Medical Center
Phoenix, Arizona, 85020, United States
WCCT Global LLC
Costa Mesa, California, 92626, United States
Advanced Rx Clinical Research
Garden Grove, California, 92843, United States
Torrance Clinical Research Institute, Inc.
Lomita, California, 90717, United States
University of Southern California
Los Angeles, California, 90033, United States
University of California at San Diego
San Diego, California, 92103, United States
Westlake Medical Research (CA)
Thousand Oaks, California, 91360, United States
Los Angeles BioMedical Research Institute
Torrance, California, 90502, United States
Empire Clinical Research
Upland, California, 91786, United States
University of Colorado
Aurora, Colorado, 80045, United States
Centennial - IMMUNOe International Research
Centennial, Colorado, 80112, United States
University of Florida
Gainesville, Florida, 32610, United States
Best Quality Research Inc.
Hialeah, Florida, 33016, United States
San Marcus Research Clinic, Inc.
Miami, Florida, 33015, United States
Medical Consulting Center
Miami, Florida, 33125, United States
Suncoast Research Group, LLC
Miami, Florida, 33135, United States
University of Miami
Miami, Florida, 33136, United States
DMI Research, Inc.
Pinellas Park, Florida, 33782, United States
Northwestern University
Chicago, Illinois, 60611, United States
Sneeze, Wheeze & Itch Associates, LLC
Normal, Illinois, 61761, United States
Ridge Family Practice
Council Bluffs, Iowa, 51503, United States
University of Iowa
Iowa City, Iowa, 52246, United States
Research Integrity, LLC
Owensboro, Kentucky, 42303, United States
Horizon Research Group, of Opelousas, LLC
Eunice, Louisiana, 70535, United States
Centex Studies Inc. - Dr. Seep
Lake Charles, Louisiana, 70601, United States
NIH Clinical Center
Bethesda, Maryland, 20892, United States
Boston Medical Center
Boston, Massachusetts, 02111, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
UMass Medical School
Worcester, Massachusetts, 01655, United States
Henry Ford Health Systems
Detroit, Michigan, 48202, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007, United States
West Florissant Internists
Bridgeton, Missouri, 63044, United States
Clinical Research Advantage/ Skyline Medical Center
Elkhorn, Nebraska, 68022, United States
Prairie Fields Family Medicine
Fremont, Nebraska, 68025, United States
Southwest Family Physicians
Omaha, Nebraska, 68124, United States
New Jersey Medical School
Newark, New Jersey, 07103, United States
Icahn School of Medicine at Mount Sinai
New York, New York, 10029, United States
University of Rochester Medical Center
Rochester, New York, 14642, United States
James J. Peters, VA Medical Center
The Bronx, New York, 10468, United States
University of North Carolina-Chapel Hill
Chapel Hill, North Carolina, 27514, United States
Duke University
Durham, North Carolina, 27710, United States
Clinical Research Solutions - Dr. Panuto
Middleburg Heights, Ohio, 44130, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213, United States
Montgomery Medical
Smithfield, Pennsylvania, 15478, United States
Health Concepts
Rapid City, South Dakota, 57702, United States
Clinical Research Solutions - Dr. Bart
Columbia, Tennessee, 38401, United States
Clinical Research Solutions - Dr. Slandzicki
Franklin, Tennessee, 37064, United States
Clinical Research Solutions - Dr. Hoppers
Jackson, Tennessee, 38305, United States
Holston Medical Group
Kingsport, Tennessee, 37660, United States
Clinical Research Solutions - Dr. Rowe
Nashville, Tennessee, 37211, United States
Clinical Research Solutions - Dr. Dar
Smyrna, Tennessee, 37167, United States
University of Texas Tech Amarillo
Amarillo, Texas, 79106, United States
Family Medicine Associates of Texas
Carrollton, Texas, 75010, United States
3rd Coast Research Associates
Corpus Christi, Texas, 78413, United States
University of Texas at Houston
Houston, Texas, 77030, United States
Centex Studies Inc. - Dr. Pouzar
Houston, Texas, 77062, United States
Pioneer Research Solutions, Inc.
Houston, Texas, 77098, United States
Texas Tech HSC
Lubbock, Texas, 79430, United States
Centex Studies Inc. - Dr. Garcia
Pharr, Texas, 78577, United States
Village Health Partners
Plano, Texas, 75024, United States
Endeavor Clinical Trials
San Antonio, Texas, 78229, United States
Bandera Family Healthcare Research
San Antonio, Texas, 78249, United States
University of Virginia
Charlottesville, Virginia, 22908, United States
Virginia Commonwealth University
Richmond, Virginia, 23298, United States
Instituto Medico Platense
La Plata, Buenos Aires, Argentina
Hospital Houssay
Vicente López, Buenos Aires, Argentina
Centro de Educación Médica e Investigaciónes Clínicas (CEMIC)
Buenos Aires, Argentina
Fundación del Centro de Estudios Infectológicos (FUNCEI)
Buenos Aires, Argentina
Hospital General de Agudos J. M. Ramos Mejía
Buenos Aires, Argentina
Hospital Italiano de Buenos Aires
Buenos Aires, Argentina
Hospital Rawson
Córdoba, Argentina
Instituto Centralizado de Asistencia e Investigación Clínica Integral (CAICI)
Santa Fe, Argentina
Holdsworth House Med Practice
Darlinghurst, New South Wales, 2010, Australia
Taylor Square Private Clinic
Darlinghurst, New South Wales, 2010, Australia
Westmead Hospital
Westmead, New South Wales, Australia
Royal Brisbane
Herston, Queensland, 4029, Australia
Northside Clinic
Fitzroy North, Victoria, 3068, Australia
The Alfred Hospital
Melbourne, Victoria, 3004, Australia
Royal Melbourne Hospital
Parkville, Victoria, 3052, Australia
Instituto Nacional de Ciencias Médicas y Nutrición (INCMN) Salvador Zubirán
México, Mexico
Hospital General y de Alta Especialidad "Dr. Manuel GEA Gonzalez"
Tlalpan, Mexico
Instituto Nacional de Enfermedades Respiratorias (INER)
Tlalpan, Mexico
Siriraj Hospital, Mahidol University
Bangkoknoi, Bangkok, 10700, Thailand
HIV-NAT, The Thai Red Cross AIDS
Patumwan, Bangkok, 10330, Thailand
Srinagarind Hospital, Khon Kaen University
Muang, Changwat Khon Kaen, 40002, Thailand
Bamrasnaradura Infectious Diseases Institute
Muang, Changwat Nonthaburi, 11000, Thailand
Related Publications (4)
Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003 Jan 8;289(2):179-86. doi: 10.1001/jama.289.2.179.
PMID: 12517228BACKGROUNDMonto AS. Vaccines and antiviral drugs in pandemic preparedness. Emerg Infect Dis. 2006 Jan;12(1):55-60. doi: 10.3201/eid1201.051068.
PMID: 16494718BACKGROUNDMoscona A. Oseltamivir resistance--disabling our influenza defenses. N Engl J Med. 2005 Dec 22;353(25):2633-6. doi: 10.1056/NEJMp058291. No abstract available.
PMID: 16371626BACKGROUNDBeigel JH, Bao Y, Beeler J, Manosuthi W, Slandzicki A, Dar SM, Panuto J, Beasley RL, Perez-Patrigeon S, Suwanpimolkul G, Losso MH, McClure N, Bozzolo DR, Myers C, Holley HP Jr, Hoopes J, Lane HC, Hughes MD, Davey RT; IRC003 Study Team. Oseltamivir, amantadine, and ribavirin combination antiviral therapy versus oseltamivir monotherapy for the treatment of influenza: a multicentre, double-blind, randomised phase 2 trial. Lancet Infect Dis. 2017 Dec;17(12):1255-1265. doi: 10.1016/S1473-3099(17)30476-0. Epub 2017 Sep 22.
PMID: 28958678DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- John Beigel, M.D.
- Organization
- Leidos Biomedical Research, Inc. is support to the National Institute of Allergy and Infectious Diseases (NIAID)
Study Officials
- STUDY CHAIR
John Beigel, MD
Leidos Biomedical Research, Inc. in support of Clinical Research Section, LIR, NIAID, Natinal Institutes of Health
- STUDY CHAIR
John Treanor, MD
University of Rochester
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 22, 2010
First Posted
October 25, 2010
Study Start
September 1, 2010
Primary Completion
May 2, 2016
Study Completion
March 30, 2017
Last Updated
February 4, 2019
Results First Posted
July 11, 2017
Record last verified: 2019-01