Different Regimens in Influenza Postexposure Chemoprophylaxis in Children

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

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.

Study Overview

• Status: Unknown
• Conditions: Influenza; Prevention; Exposure
• Intervention / Treatment: Drug: Oseltamivir 3 days; Drug: Oseltamivir 7 days

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Mazowieckie
    • Warsaw, Mazowieckie, Poland, 01-813
      • Recruiting
      • The Centre of Postgraduate Medical Education
      • Contact: August E. Wrotek, MD PhD; Phone Number: (+48)228641167; Email: august.wrotek@bielanski.med.pl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

Collaborators and Investigators

• Sponsor: Centre of Postgraduate Medical Education
• Investigators: Principal Investigator: August E. Wrotek, MD PhD, The Centre of Postgraduate Medical Education

Publications and helpful links

General Publications

• Ishiguro N, Oyamada R, Nasuhara Y, Yamada T, Miyamoto T, Imai S, Akizawa K, Fukumoto T, Iwasaki S, Iijima H, Ono K. Three-day regimen of oseltamivir for postexposure prophylaxis of influenza in wards. J Hosp Infect. 2016 Oct;94(2):150-3. doi: 10.1016/j.jhin.2016.05.012. Epub 2016 May 25.

Helpful Links

• Three-day regimen of oseltamivir for postexposure prophylaxis of influenza in wards.

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2016
• Primary Completion (Actual): March 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: February 18, 2020
• First Submitted That Met QC Criteria: March 3, 2020
• First Posted (Actual): March 5, 2020

Study Record Updates

• Last Update Posted (Actual): September 9, 2020
• Last Update Submitted That Met QC Criteria: September 7, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: influenza; child; infant; oseltamivir; chemoprevention
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Oseltamivir
• Other Study ID Numbers: 77/PB/2016

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No