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

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by:
National Institute for Public Health and the Environment (RIVM)
ClinicalTrials.gov Identifier:
NCT01053377
First received: January 19, 2010
Last updated: January 20, 2010
Last verified: December 2009
  Purpose

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.


Condition Intervention Phase
Influenza
Drug: Tamiflu (verum)
Drug: Tamiflu placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: A Randomised Controlled Trial on the Effect of Post-exposure Oseltamivir Prophylaxis on Influenza Transmission in Nursing Homes

Resource links provided by NLM:


Further study details as provided by National Institute for Public Health and the Environment (RIVM):

Primary Outcome Measures:
  • Transmission of influenza from person to person [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 900
Study Start Date: December 2009
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tamiflu Drug: Tamiflu (verum)
Placebo Comparator: Placebo Tamiflu Drug: Tamiflu placebo

Detailed 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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Exclusion Criteria:

  • Kidney dialyses
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01053377

Locations
Netherlands
Institute of Public Health and the Environment
Bilthoven, Utrecht, Netherlands, 3720 BA
Sponsors and Collaborators
National Institute for Public Health and the Environment (RIVM)
ZonMw: The Netherlands Organisation for Health Research and Development
  More Information

Additional Information:
No publications provided

Responsible Party: Marianne van der Sande, Institute of Public Health and the Environment
ClinicalTrials.gov Identifier: NCT01053377     History of Changes
Other Study ID Numbers: NL27938.041.09
Study First Received: January 19, 2010
Last Updated: January 20, 2010
Health Authority: The Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by National Institute for Public Health and the Environment (RIVM):
Influenza
Tamiflu
Osteltamivir
Transmission
Prevention
Resistance
Post-Exposure Profylaxe

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Oseltamivir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014