Different Regimens in Influenza Postexposure Chemoprophylaxis in Children

Study Overview
=================
Brief Summary
-----------------
Although the vaccination is the preferred method of influenza prevention, there are some occasions on which a postexposure prophylaxis (PEP) is required. Two neuraminidase inhibitors (NAIs) may be used in chemoprophylaxis in children: oral oseltamivir, and inhaled zanamivir. Both, oseltamivir and zanamivir, are effective in treatment and in prophylaxis of influenza, and the efficacy is calculated to reach 70-90%. Oseltamivir is used more frequently, since zanamivir is licensed in older children (5 years of age and above), and children under the age of 5 years are at higher risk of influenza complications. Oseltamivir use correlated in children with higher risk of vomiting, with no increased risk of other adverse events, including those observed in adult patients (nausea, renal events, and psychiatric effects). The PEP may be indicated by individual patient's characteristics (e.g. patients in high-risk group) or epidemiological reasons, i.e. prevention of institutional outbreaks.The one research that analyzed efficacy of 3-days PEP versus 7 or 10-days and showed overall efficacy of shorter oseltamivir prophylaxis to be high and comparable to that of longer regimens. The study included several pediatric patients and made the investigators perform such an analysis in pediatric population. In this randomized controlled trial, the investigators aimed to compare efficacy, safety, and costs of 3 versus 7-days prophylaxis with oral oseltamivir in children hospitalized. The hypothesis is that 3-days duration of PEP is not less effective than 7-days PEP, and patients might gain from lower number of adverse reactions related to drug administration.

Detailed Description
-----------------
Only applies to patients hospitalized due to other than influenza reasons. If a proven contact with influenza has taken place (influenza diagnosed by signs/symptoms and positive rapid influenza diagnostic test and/or PCR), a patient may be enrolled.

Official Title
-----------------
Efficacy of Different Regimens in Influenza Postexposure Chemoprophylaxis With Oral Neuraminidase Inhibitor in Children

Conditions
-----------------
Influenza, Exposure, Prevention

Intervention / Treatment
-----------------
* Drug: Oseltamivir 3 days
* Drug: Oseltamivir 7 days


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patients hospitalized at the Pediatric Ward age: 0-18 years old confirmed contact with a person diagnosed with influenza patient's, patient's parent/tutor's informed consent Exclusion Criteria: lack of an informed consent more than 48 hours after the first contact with influenza severe adverse reaction to the drug- discontinuation of the prophylaxis important to a parent/tutor drug intolerance (e.g. lack of tolerance of a drug's taste) new contact with influenza after chemoprophylaxis has finished

Ages Eligible for Study
-----------------
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients randomly allocated into 3 or 7-days postexposure chemoprophylaxis group
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3-days postexposure chemoprophylaxis<br>Oseltamivir given orally, 3mg per each body kg, once a day during three consecutive days after the contact with influenza | Drug: Oseltamivir 3 days<br>* Non-inferiority study of 3 versus 7-days duration of PEP<br>* Other names: 3-days postexposure chemoprophylaxis with oseltamivir;|
| Active Comparator: 7-days postexposure chemoprophylaxis<br>Oseltamivir given orally, 3mg per each body kg, once a day during seven consecutive days after the contact with influenza | Drug: Oseltamivir 7 days<br>* Active comparator<br>* Other names: 7-days postexposure chemoprophylaxis with oseltamivir;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postexposure chemoprophylaxis efficacy | Percent of patients who did not have influenza in each study arm. | up to 7 days after PEP has finished | 
| Oseltamivir safety | Presence of the following adverse reactions to drug (in percents): nausea, vomiting, skin hypersensitivity (including rash), sleep disorders, consciousness disorders, convulsions, fever related to drug administration, symptomatic arrhythmias, behavioral changes | up to 7 days after PEP has finished | 
| Postexposure chemoprophylaxis costs | Cost of drugs used in each arm, costs of treatment of adverse reactions | up to 7 days after PEP has finished | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Need for hospitalization in case of influenza after failed chemoprophylaxis | A need for hospitalization if influenza is present within 7 days after PEP completion | Up to 28 days | 
| Duration of influenza signs and symptoms after failed chemoprophylaxis | Length of period when signs and symptoms are present | Up to 28 days | 
| Presence of complications in case of influenza after failed chemoprophylaxis | Presence of influenza complications: pneumonia, bronchitis, otitis media, need for antibiotic treatment, neurological sequelae, ICU transfer, death | Up to 28 days | 
| Fever in case of influenza after failed chemoprophylaxis | Highest fever and duration of fever | Up to 28 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
influenza, chemoprevention, oseltamivir, child, infant