InfluenzaPhase 4PEPpIENCT01053377
A Randomised Controlled Trial on the Effect of Post-exposure Oseltamivir Prophylaxis on Influenza Transmission in Nursing Homes
A Phase 4 study testing Tamiflu (verum) in people with Influenza, run by National Institute for Public Health and the Environment (RIVM) at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Influenza
- What is being tested?
- Tamiflu (verum)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 900 participants
- Where
- 1 siteNetherlands
- Study dates
- Dec 2009to Dec 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Kidney dialyses
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Institute of Public Health and the Environment
Bilthoven, Utrecht, 3720 BA
About this study
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.
Read the 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.
- Conditions
- Influenza
- Being tested
- Tamiflu (verum), Tamiflu placebo
- Keywords
- Influenza, Tamiflu, Osteltamivir, Transmission, Prevention, Resistance, Post-Exposure Profylaxe
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tamiflu (verum)Drug
Tamiflu placeboDrug
| Study group | Role | What they receive |
|---|---|---|
| Tamiflu | Active comparator | Not described Receives: Drug: Tamiflu (verum) |
| Placebo Tamiflu | Placebo comparator | Not described Receives: Drug: Tamiflu placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Transmission of influenza from person to person
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2010 (estimated)
- Study startDec 2009
- Primary completionDec 2013 (estimated)
- Study completionDec 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 900 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute for Public Health and the Environment (RIVM)
- Sponsor type
- Other government
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01053377
- Sponsor's protocol ID
- NL27938.041.09
- Acronym
- PEPpIE
- Status last verified
- Dec 2009
- First submitted
- 19 Jan 2010
- Last updated
- 21 Jan 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Controlled Trial on the Effect of Post-exposure Oseltamivir Prophylaxis on Influenza Transmission in Nursing Homes
- ClinicalTrials.gov ID
- NCT01053377
- Acronym / sponsor ID
- PEPpIE / NL27938.041.09
- Conditions
- Influenza
- Keywords
- Influenza, Tamiflu, Osteltamivir, Transmission, Prevention, Resistance, Post-Exposure Profylaxe
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 900 participants (estimated)
- Lead sponsor
- National Institute for Public Health and the Environment (RIVM)Other government
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- Dec 2009
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Dec 2013 (estimated)
- First posted
- 21 Jan 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tamiflu | Active comparator | Drug: Tamiflu (verum) |
| Placebo Tamiflu | Placebo comparator | Drug: Tamiflu placebo |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (1 listed)
- Kidney dialyses
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tamiflu (verum) | Drug | Tamiflu |
| Tamiflu placebo | Drug | Placebo Tamiflu |
Primary outcome
Transmission of influenza from person to person
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2010.
- Research siteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tamiflu (verum) in people with Influenza, run by National Institute for Public Health and the Environment (RIVM) at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Jan 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Transmission of influenza from person to person (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2010.