Estudio doble-ciego, randomizado, estratificado, multicéntrico que evalua la dosis convencional y alta de oseltamivir en el tratamiento de pacientes con gripe inmunocomprometidos.
- Conditions
- Profilaxis estacional de la gripe en pacientes inmunocomprometidos (receptores de un transplante).MedDRA version: 8.1Level: LLTClassification code 10022000Term: Influenza
- Registration Number
- EUCTR2006-002468-24-ES
- Lead Sponsor
- F.Hoffmann-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 250
• 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 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 in children OR
- For patients whose most recent creatinine clearance in the 6 months prior to randomization is < 30 ml/min in adults and < 30 ml/min /1.73M2 in children, baseline creatinine clearance > 10 ml/min in adults and > 10 ml/min /1.73M2 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
• 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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:<br>• The clinical course of influenza (fever, symptoms, secondary illnesses as evidenced by otitis media, bronchitis, pneumonia, or sinusitis) <br>• The virologic course of influenza (proportion shedding and viral loads at different time points)<br>• Patient safety and tolerability <br>• The development of resistant influenza virus<br>• To characterize the population pharmacokinetics of oseltamivir (e.g. clearance, volume of distribution) in transplant recipients <br>;Primary end point(s): The primary endpoint in this study is the time to alleviation of all clinical influenza symptoms (recorded in the diary card).
- Secondary Outcome Measures
Name Time Method