To investigate the optimal therapy for influenza in immunocompromised transplant recipients. MedDRA version: 8.1 Level: LLT Classification code 10022000 Term: Influenza
Conditions
Interventions
Trade Name: Tamiflu
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: oseltamivir phosphate
Concentration unit: mg/ml milligram(s)/mi
Sponsors
F.Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age greater than or equal to 1 year • Rapid diagnostic test positive for influenza in the 24 hours prior to first dose • Immunocompromised subject defined as documented: - SOT (liver, kidney or both) recipient OR - Allogenic HSCT • Receiving ongoing immunosuppression, OR, in the investigator’s opinion, not immune reconstituted • Symptoms suggestive of influenza like illness including, but not limited to fever, cough, or coryza • Less or equal 48 hours between onset of influenza like illness and first dose of study drug • Acceptable renal function defined as: - Most recent creatinine clearance in the 6 months prior to randomization is > 30 ml/min in adults and > 30 ml/min /1.73M2 (metre squared) in children. Creatinine clearance estimated from serum creatinine measured when subject is not receiving any renal replacement therapy OR - For patients who have not had a creatinine clearance assessment in the 6 months prior to randomization, baseline creatinine clearance > 10 ml/min in adults and > 10 ml/min /1.73M2 (metre squared) in children OR - For patients whose most recent creatinine clearance in the 6 months prior to randomization is 10 ml/min in adults and > 10 ml/min /1.73M2 (metre squared) in children • Parent/guardian willing and able to comply with study requirements and give consent. (country specific age cut off) • Patient able to comply with study requirements and willing to give assent, as appropriate (country specific age cut off) • For adult patients, willing and able to comprehend and give written informed consent • Patients, in the reproductive age group, must agree to utilize an effective method of contraception throughout the study period and for one reproductive cycle following cessation of study therapy • Females of childbearing potential must have a negative urine pregnancy test prior to start of study medication Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • SOT within 6 months of the time of randomization • Solid Organ Transplant other than liver, kidney or liver and kidney • Have in the investigator’s opinion experienced acute rejection in the 4 weeks prior to randomization • HSCT patients with no evidence of engraftment (engraftment is defined as the point at which a patient can maintain a sustained absolute neutrophil count (ANC) of >500/mm3 and sustained platelet count of =20,000/mm3, lasting =3 consecutive days without transfusions) • HSCT subjects not discharged from hospital after their initial hospitalization for transplantation • Have evidence of veno-occlusive disease, acute or chronic extensive graft versus host disease at the time of randomization • Have clinical evidence for hepatic decompensation at the time of randomization (clinical icterus, ascites, hepatic encephalopathy, coagulopathy) • Have cirrhosis of the liver at the time of randomization • Currently or in the six months prior to randomization using T cell depleting antibodies (example: antithymocyte globulin, antilymphocyte globulin) for management of transplant • Have other co-morbid conditions that could affect patient survival or graft function including, but not limited to, a post-transplant lymphoproliferative disease (PTLD), autoimmune disease including inflammatory bowel disease and psoriasis, untreated thyroid disease, and significant active infection • Patients currently receiving any form of renal replacement therapy including hemodialysis, peritoneal dialysis or hemofiltration • Have evidence of active or uncontrolled opportunistic infections (bacterial, fungal, or viral - including cytomegalovirus [CMV] or polyoma virus [BKV]) at the time of randomization. Patients with HCV or HBV are not excluded. • Patients with known HIV infection • Patients who are being evaluated or treated for an active malignancy (other than the malignancy for which the SOT or HSCT may have been performed) at the time of randomization • Patients with uncontrolled vascular, neurologic or pulmonary disease. Uncontrolled is defined as disease requiring change of therapy or hospitalization in the 4 weeks preceding randomization. Change of therapy is defined as dose increase or change of medication prior to onset of present influenza like illness. • Patients with severe diarrhea or other gastrointestinal disorders which might interfere with their ability to absorb oral medication, including diabetic patients with previously diagnosed diabetic gastroenteropathy • Allergy to the test medication • Patients with hereditary fructose intolerance (for subjects who will be taking the liquid formulation) • Influenza vaccination in the 2 weeks prior to randomization • Antiviral treatment (example: amantadine, rimantadine, zanamivir and ribavirin) for influenza in the 2 weeks prior to randomization • Patients taking probenecid medication • Patients who are pregnant or breast-feeding • Participation in a clinical trial or expanded access trial with an investigational drug in the 4 weeks prior to randomization or concomitantly with this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate prospectively the efficacy of oseltamivir for the treatment of influenza in transplant recipients as measured by the time to resolution of influenza symptoms; Secondary Objective: To evaluate the effects of conventional and high dose oseltamivir in transplant recipients on: • The clinical course of influenza (fever, symptoms, secondary illnesses as evidenced by otitis media, bronchitis, pneumonia, or sinusitis) • The virologic course of influenza (proportion shedding and viral loads at different time points) • Patient safety and tolerability • The development of resistant influenza virus ;Primary end point(s): The primary endpoint in this study is the time to resolution of all influenza symptoms as recorded in the patient diary. | — |
Countries
Belgium, Bulgaria, Czech Republic, Estonia, France, Germany, Greece, Hungary, Italy, Latvia, Lithuania, Spain, United Kingdom
Outcome results
None listed