TCAD vs. Monotherapy for Influenza A in Immunocompromised Patients

Inclusion Criteria: i. Inclusion criteria for randomized arms (both needed): 1. Age ≥7 years, male or female; AND 2. Influenza infection (i.e. upper respiratory tract infection) ii. Inclusion criteria for open-label arm (at least one criteria required): 1. Young age (1-6 years) with any influenza severity, proven or probable influenza A (H1N1)(H274Y); OR 2. History of asthma; OR 3. Older age (≥ 7 years), with no asthma; AND * moderate to severe influenza; AND/OR * failure in randomized study monotherapy arm iii. Inclusion criteria for all subjects: 1\. Able to provide informed consent, or for whom consent may be provided by guardian 2. Immunocompromised, as defined by one of the following: * Recent hematopoietic cell transplantation (HCT) (within 2 years, all conditioning regimens, allogeneic, autologous, syngeneic; after 2 years patients with chronic graft-versus-host disease (GVHD) requiring systemic treatment may be included) or solid organ transplantation * Patients taking at least 2 immunosuppressants * Patients undergoing combination chemotherapy within the past 3 month 3. One or more of the following: * Presence of fever at time of screening of ≥ 38.0°C (≥ 100.0°F) taken orally. * presence of at least one constitutional symptom (headache, myalgia, malaise, or fatigue) of any severity (mild, moderate, or severe), * presence of at least one respiratory symptoms (e.g. cough, or sore throat) of any severity (mild, moderate, or severe), * other flu-like symptoms, where the clinician orders a respiratory virus test including influenza A or B 4. Positive test for influenza A (if available) 5. Onset of illness no more than 5 days prior to diagnosis. 6. Females patients of child-bearing age who are capable of conception (i.e. previously have not undergone surgical sterilization) must meet the following criteria: * Have been sexually abstinent or have used contraceptive agents (oral contraceptive or other hormonal contraceptives including vaginal rings or transdermal patches, intrauterine device (IUD), or barrier methods including condoms) during the 4 weeks prior to date of screening (3 months prior to enrollment for oral/hormonal contraceptives) * Agree to be sexually abstinent or use contraceptive agents (oral contraceptive or other hormonal contraceptives including vaginal rings or transdermal patches, intrauterine device (IUD), or barrier methods including condoms) from the date of screening through 24 weeks after the last dose of study drug Exclusion Criteria(all subjects): 1. Nausea that prevents taking oral medications 2. Use of antiviral influenza medication within 10 days(unless switched from randomized to open-label TCAD). An exception to this exclusion criterion may be made by site investigators for patients admitted after hours who receive one or two initial doses of antiviral influenza medication prior to enrollment. 3. Creatinine clearance (estimated by serum creatinine) less than 30 ml/min 4. Current clinical evidence of a recognized or suspected uncontrolled non-influenza infectious illness with onset prior to screening 5. Known hypersensitivity to amantadine, ribavirin, oseltamivir or zanamivir 6. Women who are pregnant (positive serum or urine pregnancy test), who are attempting to become pregnant, or who are breast-feeding 7. Psychiatric or cognitive illness, or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect patient safety and/or compliance 8. Uncontrolled seizure disorder or history of a seizure activity within 12 months prior to study participation 9. Any significant finding in the patient's medical history or physical exam on Day 1 that, in the opinion of the investigator, would affect patient safety or compliance with the dosing schedule 10. Documented Influenza B viral co-infection