A double blind, randomized, placebo controlled, multi-center trial of oseltamivir for the seasonal prophylaxis of influenza in immunocompromised patients

• Conditions: Seasonal prophylaxis of influenza in immonucompromised subjects; MedDRA version: 8.1Level: LLTClassification code 10022000Term: Influenza

• Registration Number: EUCTR2006-002473-47-LT
• Lead Sponsor: F.Hoffmann-La Roche Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-11-06
• Last Update Posted: 12 June 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 470

Inclusion Criteria

•Age greater than or equal to 1 year
•Negative rapid diagnostic test for influenza at baseline
•Immunocompromised subject defined as documented:
SOT (liver, kidney or both) recipient OR
Allogenic HSCT
•Parent/guardian willing and able to comply with study requirements and give consent (country specific age cut off).
•Subject able to comply with study requirements and willing to give assent (for minors, country specific age cut off), as appropriate
•For adult subjects, willing and able to comprehend and give written informed consent
•Subjects, 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? no
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

•Symptoms suggestive of influenza-like illness including but not limited to fever, cough, or nasal congestion
•Subjects with fever (temperature > or = 37.8 deg Celsius)
•Influenza vaccination in the 6 weeks prior to randomization
•Positive rapid diagnostic test for influenza
•SOT within 6 months of the time of randomization
•SOT 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 > or = 20,000/mm3, lasting > or = 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
•Currently or previously administered lymphocyte depleting monoclonal 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
•Estimated creatinine clearance < 10 ml/min in adults or < 10 ml/min/1.73 M2 in children (Cockroft-Gault equation for adults and the Schwartz equation in children)
•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 at the time of randomization excluding malignancies for which the SOT or HSCT may have been performed.
•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.
•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
•Hereditary fructose intolerance (for subjects who will e taking the liquid formulation)
•Antiviral treatment (example: amantadine, rimantadine, zanamavir, oseltamivir 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 an expanded access trial with an investigational drug in the 4 weeks prior to randomization or concomitantly with this study . Patients enrolled in this study can not be enrolled in another study for either research, diagnostic or treatment purposes.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the study is to evaluate prospectively the efficacy of oseltamivir in the seasonal prophylaxis of influenza as measured by the relative incidence of laboratory confirmed clinical influenza in the two treatment groups.;Secondary Objective: The secondary objectives of the study are to evaluate:<br>- The efficacy of oseltamivir for the seasonal prophylaxis of influenza as measured by the relative incidence of influenza in the two treatment groups<br>- The safety of oseltamivir prophylaxis in immunocompromised populations as evaluated by the review of adverse events, laboratory parameters, vital signs and physical exam in the two treatment groups.<br>- The evaluation of all isolates for phenotypic and where necessary genotypic resistance.;Primary end point(s): the proportion of subjects with laboratory confirmed clinical influenza in the two treatment arms.