A Randomised Controlled Trial on the Effect of Post-exposure Oseltamivir Prophylaxis on Influenza Transmission in Nursing Homes

Influenza Clinical Trial

— PEPpIE  

Official title:

A Randomised Controlled Trial on the Effect of Post-exposure Oseltamivir Prophylaxis on Influenza Transmission in Nursing Homes

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT01053377
• Other study ID #: NL27938.041.09
• Status: Enrolling by invitation
• Phase: Phase 4
• First received: January 19, 2010
• Last updated: January 20, 2010
• Start date: December 2009
• Est. completion date: December 2013

Study information

• Verified date: December 2009
• Source: National Institute for Public Health and the Environment (RIVM)
• Contact: n/a
• Is FDA regulated: No
• Health authority: The Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial Summary

The incidence of severe morbidity and mortality following an influenza infection during the annual influenza epidemics is highest among the elderly population and 90% of influenzaassociated mortality occurs in this group. Vaccination is considered the best preventive intervention available but offers only partial protection. The protective effect decreases with advancing age and existing co-morbidity. Therefore, in spite of high compliance with vaccination, the risk of influenza-related complications among nursing-home residents, is particularly high, and consequently also the associated disease and economic burden. There is debate on the potential health benefit of the antiviral activity of oseltamivir as an effective supplementary intervention to prevent or contain influenza outbreaks in nursing homes. Although effectiveness of post-exposure prophylaxis (PEP) with oseltamivir on preventing transmission has been demonstrated in trials among healthy (mainly unvaccinated) adults and children, effectiveness has not yet been assessed among vulnerable vaccinated highrisk groups, such as the elderly population in nursing homes. If proven (cost)effective, oseltamivir could have considerable benefits in this setting, although constraints relating to implementation need to be addressed as well.

Description:

Objective If proven (cost)effective, without inducing antiviral resistance, oseltamivir could have considerable benefits in this setting, although constraints relating to implementation need to be addressed as well. If not (cost)effective if this fragile population, resources can be better spent on other activities to support nursing home residents.

Study design:

A randomised controlled trial on the effect of PEP with oseltamivir versus placebo on transmission of influenza in nursing homes, linked to virological monitoring of possible development of resistance and impact on transmission and outcome, linked with a cost effectiveness analysis, and an exploration of logistical and ethical issues which could interfere with successful implementation.

Study population:

This trial will be nested in the recently established Network of Nursing Homes (SNIV). SNIV has been initiated and is coordinated by the RIVM Centre of Infectious Disease Control. Baseline data on the population in these nursing homes is already routinely collected, and epidemiological and virological surveillance of ILI/influenza is established, in collaboration with the local laboratories.

Intervention:

Post-exposition prophylaxis with oseltamivir or placebo. Once laboratory confirmation has been obtained in an index case, all residents of that implicated unit only will be randomly assigned to PEP with either oseltamivir 75 mg or placebo once daily for 10 days. Data on co-morbidity, medication and other potential confounders for susceptibility to a clinical influenza infection will be collected prior to the start of PEP. The index patient (and any secondary patients) will be treated therapeutically with oseltamivir. Main study parameters/endpoints: Transmission, the primary trial outcome measurement, is defined as a newly laboratory confirmed influenza in the same unit 12 hours or more after the start of PEP. Assuming 30 homes participate, that annually 30% of nursinghomes experience a confirmed influenza outbreak in on average two units, than we can recruit 20 units per season. Assuming that without effective prophylaxis ongoing transmission occurs in 40% of the units, we will have at least 80% power after 3 seasons with a two-sided alpha=0.05 to demonstrate a reduction in transmission of 70%.

Furthermore, this trial offers an excellent opportunity to evaluate the possible emergence of resistance against oseltamivir if used under such circumstances, by analysing the occurrence of viral mutations under oseltamivir therapy (for index- and for any secondary cases). In addition, we will assess the relative cost-effectiveness of PEP with oseltamivir per nursing home unit, compared to not using PEP by prospectively collecting information on the number of influenza infections and related complications, duration of symptoms, use of medical services by secondary cases, as well as sickness leave of staff.

Finally, potential ethical and logistical restrictions for the large scale use of oseltamivir will be documented prospectively.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

Burden and risks of this trial will be minimal, as we will not deviate from current standing practices, in which some nursing homes offer PEP and others don't, following the diagnosis of influenza on a unit.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 900
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A and older

Eligibility

Exclusion Criteria:

• Kidney dialyses

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Drug:
• Tamiflu (verum)

• Tamiflu placebo

Locations

Country	Name	City	State
Netherlands	Institute of Public Health and the Environment	Bilthoven	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
National Institute for Public Health and the Environment (RIVM)	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Transmission of influenza from person to person		3 months	No