If proven (cost)effective, without inducing antivral 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…
ID
Source
Brief title
Condition
- Viral infectious disorders
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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%.
Secondary outcome
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
Background 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 influenza-associated 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
high-risk 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.
Study objective
If proven (cost)effective, without inducing antivral 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 on
transmission of influenza in nursing homes, linked to virological monitoring of
possible development of resistance and impact on transmission and outcome, a
cost effectiveness analysis, and an exploration of logistical and ethical
issues which could interfere with successful implementation.
Intervention
Post-exposition prophylaxis with oseltamivir or placebo.
Once laboratory confirmation has been obtained in an index case, all residents
and staff of that implicated unit only will be randomly assigned to PEP with
either oseltamivir or placebo 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.
Study burden and risks
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.
Postbus 1
3720 BA Bilthoven
NL
Postbus 1
3720 BA Bilthoven
NL
Listed location countries
Age
Inclusion criteria
The unit of randomisation will be nursing home units in nursing homes willing to participate, and where virologically confirmed influenza is diagnosed in an index case. In these units, all residents (apart from the index case(s)) and staff are eligible for randomisation to PEP with oseltamivir or PEP with placebo.
Exclusion criteria
No consent, medical contra-indication to oseltamivir.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | 2006-000749-21 |
| EudraCT | EUCTR2006-000749-21-NL |
| CCMO | NL27938.041.09 |