Trial record 1 of 1 for:    NCT01227967
Previous Study | Return to List | Next 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 (IRC003)

This study is currently recruiting participants.
Verified March 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01227967
First received: October 22, 2010
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

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 will evaluate the use of combination antivirals (amantadine, oseltamivir, and ribavirin) compared to oseltamivir alone in the treatment of influenza in an at-risk population.


Condition Intervention Phase
Influenza
Drug: Amantadine, Ribavirin, Oseltamivir
Drug: Oseltamivir
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Evaluate the reproducibility of virologic samples, comparison between culture and PCR, and the impact of missing data between randomized groups. [ Time Frame: First 50 subjects ] [ Designated as safety issue: No ]
    The specific measure used for the primary endpoint will be determined by a pilot study of the first 50 subjects randomized which will evaluate the reproducibility of virologic samples, comparison between culture and PCR, and the impact of missing data between randomized groups.


Estimated Enrollment: 1200
Study Start Date: September 2010
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination Therapy
Amantadine, Ribavirin, Oseltamivir
Drug: Amantadine, Ribavirin, Oseltamivir
One capsule of Oseltamivir 75 mg x 2 - Total dose: 150 mg/day for 5 days; Three capsules of Ribavirin 200 mg for total of 600 mg x 2 - Total dose: 1200 mg/day for 5 days; One capsule of Amantadine 100 mg x 2 Total dose: 200 mg/day for 5 days
Active Comparator: Oseltamivir monotherapy
Oseltamivir
Drug: Oseltamivir
75 mg x 2 Total dose: 150 mg/day for 5 days

Detailed Description:

Seasonal influenza is responsible for approximately 226,000 excess hospitalizations annually and despite effective antivirals causes significant morbidity and mortality (estimated 24,000-50,000 deaths each year in the United States alone). The influenza virus that emerged in 2009 (A/California/07/2009 H1N1) caused fewer deaths (12,000 flu-related deaths in the U.S) but in contrast to seasonal flu, nearly 90 percent of the deaths with the 2009 H1N1 occurred among people younger than 65 years of age. The CDC has defined an at-risk population that is responsible for the majority of hospitalization and morbidity associated with influenza. This study will evaluate the use of combination antivirals as compared to oseltamivir alone in the treatment of influenza in an at-risk population.

Subjects who meet the CDC definition for being at-risk and that present with an influenza-like illness will be screened for the study. Those subjects with a confirmatory test for influenza (rapid antigen or PCR) will be randomized in a 1:1 manner to receive a blinded study treatment consisting of either the combination of amantadine, oseltamivir, and ribavirin or oseltamivir alone for 5 days. Clinical, virologic, and laboratory assessments on Days 1, 3, 7, 14, and 28 will be used for both safety and efficacy analysis.

Objectives:

- To evaluate the effectiveness of combined treatment with oseltamivir, amantadine, and ribavirin compared with oseltamivir alone for at-risk individuals with confirmed influenza infection.

Eligibility:

- Individuals at least 18 years of age who have one or more medical conditions that may cause complications from influenza, and have developed an influenza-like illness.

Design:

  • Participants will be screened with a physical examination and medical history, along with blood tests and throat swabs to confirm influenza infection.
  • Eligible participants will be randomly assigned to take either oseltamivir alone (the current standard treatment for influenza) or to take oseltamivir, amantadine, and ribavirin. Participants will have additional blood samples and throat swabs taken at the start of the study, and will be shown how to complete a study diary at home.
  • Participants will receive a study medication kit containing the medication to take at home twice a day for 5 days.
  • Participants will return, with the medication kit, to the clinic on days 1 (the first day after the start of the study), 3, 7, 14, and 28. The first visit may take 2 to 3 hours, but each subsequent visit should take approximately 1 to 2 hours. Additional blood samples and throat swabs will be taken at these visits.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Enrollment (Screening)

  1. Signed informed consent prior to initiation of any study procedures
  2. Age greater than or equal to 18 years of age
  3. Presence of an underlying medical condition(s) that may increase risk of complications from influenza
  4. 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
    • 1 or more constitutional symptom (headache, malaise, myalgia, sweats/chills or fatigue)
  5. 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
  6. Willingness to have samples stored

Randomization

  1. Signed informed consent
  2. Age greater than or equal to 18 years of age
  3. Presence of a medical condition(s) that have been associated with increased risk of complications from influenza

    • Age 65 years of age or older
    • Asthma
    • Neurological and neuro-developmental conditions (including disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy [seizure disorders], stroke, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury) [though still able to provide informed consent per inclusion criteria #1]
    • Chronic lung disease (such as COPD and cystic fibrosis)
    • Heart disease (such as congenital heart disease, congestive heart failure, and coronary artery disease)
    • Blood disorders (excluding genetic causes of anemia, as noted in the exclusion criteria)
    • 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
  4. 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
  5. 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)

  6. One of the following to avoid pregnancy:

    • Females who are 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 have 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
  7. Willingness to have samples stored

EXCLUSION CRITERIA:

(for Enrollment or Randomization)

  1. Women who are pregnant or breast-feeding, and men whose female partner(s) is pregnant
  2. Inability to take oral medication or a history of gastrointestinal malabsorption that would preclude the use of oral medication.
  3. Hemoglobin < 10 g/dL
  4. WBC < 1.5 times 10(9)/L
  5. Neutrophils < 0.75 x 10(9)/L
  6. Platelets < 50 x 10(9)/L
  7. History of genetic hemoglobinopathy (e.g., thalassemia major or sickle cell anemia) or autoimmune hemolytic anemia
  8. Received more than 2 doses of any antiviral influenza medications since onset of influenza symptoms
  9. Received stavudine (d4T), didanosine (ddI), zidovudine (AZT), or azathioprine within 30 days prior to study entry
  10. Creatinine clearance less than 50 mL/min (estimated by the Cockcroft-Gault equation using serum creatinine)
  11. History of autoimmune hepatitis
  12. Uncompensated liver disease (defined as AST > 3 times site upper limit of normal (ULN), ALT > 3 times ULN, or Direct Bilirubin > 2 times ULN)
  13. Clinical signs of end-stage liver disease including jaundice, coagulopathy, portal hypertension, esophageal varices, ascites, peripheral edema, gastrointestinal bleeding, or encephalopathy
  14. Chronic liver disease categorized as Child-Pugh class C (Child-Pugh score 10-15)
  15. Known hypersensitivity to rimantadine, amantadine, ribavirin, oseltamivir, peramivir, or zanamivir
  16. Received live attenuated virus vaccine (influenza or other) within 3 weeks prior to study entry
  17. Use of any investigational drug within 30 days or 5 half-lives (whichever is longer) prior to study entry
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01227967

Contacts
Contact: Patient Recruitment and Public Liaison Office (800) 411-1222 prpl@mail.cc.nih.gov
Contact: TTY 1-866-411-1010

  Hide Study Locations
Locations
United States, California
WCCT Global LLC Recruiting
Costa Mesa, California, United States, 92626
Contact: Linda Gozer       Linda.Gozer@wcct.com   
Torrance Clinical Research Institute, Inc. Recruiting
Lomita, California, United States, 90717
Contact: Marina Raikhel, M.D.       marinaraikhel@hotmail.com   
University of Southern California Recruiting
Los Angeles, California, United States, 90033
Contact: Luis M. Mendez, BS    323-343-8283    lmendez@usc.edu   
University of California at San Diego Recruiting
San Diego, California, United States, 92103
Contact: Jill Kunkell, RN    619-543-8080    jkunkell@ucsd.edu   
Westlake Medical Research (CA) Recruiting
Thousand Oaks, California, United States, 91360
Contact: Krista Preston, MD         
Los Angeles BioMedical Research Institute Terminated
Torrance, California, United States, 90502
United States, Colorado
University of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: M. Graham Ray, RN, MSN    303-724-0712    graham.ray@ucdenver.edu   
United States, Florida
Best Quality Research Inc. Recruiting
Hialeah, Florida, United States, 33016
Contact: Aniuska Ruiz    786-313-3506    aniuskaruiz@bestqualityresearch.com   
University of Miami Completed
Miami, Florida, United States, 33136
Suncoast Research Group, LLC Recruiting
Miami, Florida, United States, 33135
Contact: Carolina Ramirez    305-631-6704    eramirez@suncoastresearch.com   
San Marcus Research Clinic, Inc. Recruiting
Miami, Florida, United States, 33015
Contact: Luis Canete    305-424-7420    jcanete@sanmarcusresearchclinic.com   
Medical Consulting Center Recruiting
Miami, Florida, United States, 33125
Contact: Leo Becerra    305-649-0492    leobecerra6@aol.com   
DMI Research, Inc. Recruiting
Pinellas Park, Florida, United States, 33782
Contact: Ingrid Ferro-Spilde, CCRC    727-531-2848 ext 104    mailto:iferro@dmiresearch.com   
United States, Illinois
Northwestern University Completed
Chicago, Illinois, United States, 60611
Sneeze, Wheeze & Itch Associates, LLC Recruiting
Normal, Illinois, United States, 61761
Contact: Dana Dalbak    309-452-0995    danadalbak@asthma2.com   
United States, Kentucky
Research Integrity, LLC Completed
Owensboro, Kentucky, United States, 42303
United States, Louisiana
Horizon Research Group, of Opelousas, LLC Recruiting
Eunice, Louisiana, United States, 70535
Contact: Rachael Boudreaux    337-457-8841    rachael@horizonresearchgroup.com   
United States, Maryland
NIH Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: Jocelyn Voell, RN    301-435-7913    jvoell@mail.nih.gov   
United States, Massachusetts
Boston Medical Center Completed
Boston, Massachusetts, United States, 02111
UMass Medical School Recruiting
Worcester, Massachusetts, United States, 01655
Contact: Celia Hartigan, RN    508-856-2800    celia.hartigan@umassmed.edu   
United States, Michigan
Henry Ford Health Systems Completed
Detroit, Michigan, United States, 48202
Bronson Methodist Hospital Recruiting
Kalamazoo, Michigan, United States, 49007
Contact: Gail Massey, RN, BS, CCRP    269-341-8774    masseyg@bronsonhg.org   
United States, Nebraska
Clinical Research Advantage/ Skyline Medical Center Recruiting
Elkhorn, Nebraska, United States, 68022
Contact: William Patrick Fitzgibbons, M.D.    402-393-2727      
Prairie Fields Family Medicine Recruiting
Freemont, Nebraska, United States, 68025
Contact: Shayla Addison    402-753-6034    shaylaaddison@crastudies.com   
Southwest Family Physicians Recruiting
Omaha, Nebraska, United States, 68124
Contact: Jan Mitchell    402-505-4497    JanMitchell@crastudies.com   
United States, New Jersey
New Jersey Medical School Recruiting
Newark, New Jersey, United States, 07103
Contact: Nancy Reilly, RN, MS    973-972-1268    reillyna@umdnj.edu   
United States, New York
James J. Peters, VA Medical Center Recruiting
Bronx, New York, United States, 10468
Contact: Fletcher Fernau    718-584-9000 ext 6671    Fletcher.Fernau@va.gov   
University of Rochester Medical Center Completed
Rochester, New York, United States, 14642
United States, North Carolina
University of North Carolina-Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27514
Contact: Cheryl Marcus    919-843-8761    cjm@med.unc.edu   
Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: Cameron Wolfe, MD    919-970-3885    cameron.wolfe@duke.edu   
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Matthew Freiberg, MD    412-586-9847    freibergms@upmc.edu   
United States, South Dakota
Health Concepts Recruiting
Rapid City, South Dakota, United States, 57702
Contact: Marty Beasley    605-348-4141    healthconcepts104@hotmail.com   
United States, Tennessee
Holston Medical Group Recruiting
Kingsport, Tennessee, United States, 37660
Contact: Judith L. White, M.D.    423-857-2789      
United States, Texas
University of Texas Tech Amarillo Recruiting
Amarillo, Texas, United States, 79106
Contact: Joann Urben    806-354-5582    joann.urben@ttuhsc.edu   
University of Texas at Houston Completed
Houston, Texas, United States, 77030
Pioneer Research Solutions, Inc. Recruiting
Houston, Texas, United States, 77098
Contact: Francisco J. Velazquez, M.D.    281-660-7803      
Texas Tech HSC Completed
Lubbock, Texas, United States, 79430
Bandera Family Healthcare Research Recruiting
San Antonio, Texas, United States, 78249
Contact: Christiana Adeyemi       christy@bfhcresearch.com   
United States, Virginia
University of Virginia Completed
Charlottesville, Virginia, United States, 22908
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Daniel Nixon, MD    804-828-4510    dnixon@mcvh-vcu.edu   
Argentina
Hospital Municipal "Prof. Dr. Bernardo A. Houssay" Recruiting
Vicente Lopez, Provincia de Buenos Aires, Argentina
Contact: Gustavo Lopardo, MD    (5411) 4809-4206    glopardo@intramed.net   
Centro de Educación Médica e Investigaciónes Clínicas (CEMIC) Recruiting
Buenos Aires, Argentina
Contact: Pablo Bonvehi, MD    5411-5299-1580 ext 2228    pbonvehi@intramed.net.ar   
Hospital Italiano de Buenos Aires Recruiting
Buenos Aires, Argentina
Contact: Laura Barcán, MD    5411-4959-0393    laura.barcan@hospitalitaliano.org.ar   
Hospital General de Agudos J. M. Ramos Mejía Recruiting
Buenos Aires, Argentina
Contact: Marcelo Losso, MD    5411-4931-5252    mlosso@hivramos.org.ar   
Hospital Rawson Recruiting
Cordoba, Argentina
Contact: Daniel David, MD    (54 351) 422-7452    danielo.david@gmail.com   
Australia, New South Wales
Taylor Square Private Clinic Completed
Darlinghurst, New South Wales, Australia, 2010
Holdsworth House Med Practice Completed
Darlinghurst, New South Wales, Australia, 2010
Westmead Hospital Completed
Westmead, New South Wales, Australia
Australia, Queensland
Royal Brisbane Completed
Herston, Queensland, Australia, 4029
Australia, Victoria
Northside Clinic Completed
Fitzroy North, Victoria, Australia, 3068
The Alfred Hospital Completed
Melbourne, Victoria, Australia, 3004
Royal Melbourne Hospital Completed
Parkville, Victoria, Australia, 3052
Mexico
Instituto Nacional de Ciencias Médicas y Nutrición (INCMN) Salvador Zubirán Recruiting
México City, Mexico
Contact: Francisco Astudillo, MD    (52-55) 5487-0900 ext 2420      
Contact: Itzel Cruz, MD    (52-55) 5487-0900 ext 2420      
Instituto Nacional de Enfermedades Respiratorias (INER) Recruiting
Tlalpan, Mexico
Contact: Javier Romo Garcia, MD    52 (55) 5487-1700 ext 5295      
Contact: Roberto Sanchez, MD    52 (55) 5487-1700 ext 5295      
Hospital General y de Alta Especialidad "Dr. Manuel GEA Gonzalez" Recruiting
Tlalpan, Mexico
Contact: Jose Antonio García, MD    52 (55) 15 56 8162      
Contact: Francisco Vélez, MD    52 (55) 15 56 8162      
Thailand
Siriraj Hospital, Mahidol University Recruiting
Bangkoknoi, Bangkok, Thailand, 10700
Contact: Winai Ratanasuwan, MD    +66-24-197-388    srwrt@mahidol.ac.th   
HIV-NAT, The Thai Red Cross AIDS Recruiting
Patumwan, Bangkok, Thailand, 10330
Contact: Anchalee Avihingsanon    +66-26-523-040 ext 107    anchalee.a@hivnat.org   
Srinagarind Hospital, Khon Kaen University Recruiting
Muang, Khon Kaen, Thailand, 40002
Contact: Ploenchan Chetchotisakd, MD    +66-43-363-168    ploencha@kku.ac.th   
Bamrasnaradura Infectious Diseases Institute Recruiting
Muang, Nonthaburi, Thailand, 11000
Contact: Weerawat Manosuthi    +66-25-903-632    drweerawat@hotmail.com   
Sponsors and Collaborators
Investigators
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, School of Medicine and Dentistry
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01227967     History of Changes
Other Study ID Numbers: 10-I-0210, 10-I-0210, IRC003
Study First Received: October 22, 2010
Last Updated: March 25, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Adaptive Design
At Risk
H1N1
Synergy
TCAD

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Amantadine
Antiviral Agents
Ribavirin
Oseltamivir
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Infective Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antimetabolites
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014