Simplifying the Rabies Pre-exposure Vaccination
Information source: Institute of Tropical Medicine, Belgium
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Rabies
Intervention: Human Diploid Cell Vaccine (HDCV) rabies vaccine (Biological)
Phase: Phase 3
Status: Active, not recruiting
Sponsored by: Institute of Tropical Medicine, Belgium Official(s) and/or principal investigator(s): Patrick Soentjens, MD, Principal Investigator, Affiliation: ITM and Military Hospital
Summary
Rabies is a viral zoonosis that causes an encephalitis, almost invariably fatal. It is
widely distributed across the globe: the World Health Organization (WHO) estimates that
about 2,4 billion people live in endemic areas for canine rabies. Vaccination of domestic
animals is limited to industrialized and middle-income countries.
The development of clinical rabies can be prevented through timely immunization after
exposure: however, preventive vaccination simplifies the post-exposure procedure
considerably, as immunoglobulins are no longer needed and less vaccine administrations are
scheduled. Pre-exposure prophylaxis consists of an intramuscular (IM)of intradermal (ID)
dose given on days 0, 7 and 21 or 28. The development of immunological memory after this
vaccination is critical for the establishment of long lasting immunity. Subjects receiving a
booster dose 1 year after pre-exposure prophylaxis segregate themselves into 'good' and
'poor' responders; the former may not need further boosters for 10 years, whereas the latter
may need more frequent boosters.
Until recently, guidelines in travel medicine recommended pre-exposure vaccination only for
some risk groups. Since recent studies have shown the effectiveness of the ID vaccination,
the policies are changing towards pre-exposure vaccination for a larger population,
including travelers to endemic regions, where immunoglobulins and vaccine are often not
readily available.
Based on the above, the investigators must stress the concept of "boostability" after a risk
exposure. However, the current pre-exposure vaccination scheme could be improved: a schedule
of 1 week would be less time consuming, would improve compliance and give less interference
with other prophylaxis measures, e. g. mefloquine. Two small studies suggest that a schedule
of 1 week interval is as effective and immunogenic as the standard one.
The investigators will investigate whether the accelerated schedule is as effective as the
classical schedule, by carrying out a randomized, non-inferiority study.
Clinical Details
Official title: Simplifying the Rabies Pre-exposure Vaccination
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Primary outcome: Boostability of the rabies antibodies
Secondary outcome: Rabies serologyRabies serology Serological response of booster vaccinations Adverse events Serious adverse events
Detailed description:
Rabies is a viral infection that affects the central nervous system and causes an
encephalitis which is almost invariably fatal. Being a zoonosis, the infection usually
occurs following a transdermal bite or scratch by an infected animal, but contamination may
also occur when infectious material, usually saliva, comes into direct contact with the
victim's mucosa or with fresh skin wounds. Human-to-human transmission is extremely
uncommon.
Rabies is widely distributed across the globe: the World Health Organization (WHO) estimates
that 87 countries with a total population of about 2,4 billion people are afflicted with
endemic canine rabies, and the inclusion of all species poses a potential threat to >3. 3
billion people. The number of rabid wild animals that die without being detected is however
estimated to be more than 90% of the total, so identified infections represent only a small
fraction of wild animal rabies cases. Vaccination of domestic animals is limited to
industrialized nations, the most urbanized areas of Latin America and some Asian countries
such as Thailand.
The development of clinical rabies can be prevented through timely immunization after
exposure to the infecting agent: preventive vaccination alone implies no complete
protection, but it simplifies the post-exposure procedure considerably, as immunoglobulins
are no longer needed and less vaccine administrations are scheduled. Pre-exposure
prophylaxis consists of an intramuscular (IM)of intradermal (ID) dose given on days 0, 7 and
21 or 28. The development of immunological memory after this vaccination is therefore
critical for the establishment of long lasting immunity against rabies in humans. If a
booster dose is given 1 year after pre-exposure prophylaxis, subjects segregate themselves
into 'good' and 'poor' responders; the former group, who represent 75% of subjects, may not
need further booster vaccination for 10 years, whereas the latter may need more frequent
boosters.
Until recently, guidelines in travel medicine recommended the pre-exposure vaccination only
to the classic risk groups. Since recent studies have shown the effectiveness of the ID
vaccination, the policies are changing towards the recommendation of pre-exposure
vaccination for a larger population, including all travelers to endemic regions, where
rabies immunoglobulins and vaccine are often not readily available. The ID pre-exposure
vaccination, which is more cost-effective, could also become an affordable alternative to
protect the local population in high endemic regions.
Based on all the above, the investigators must stress the concept of "boostability" after a
risk exposure: the main target of travel medicine today is to get a sufficient serological
response on day 7 after a risk in prevaccinated persons (accelerated immune response through
memory cells) and after two post-exposure vaccinations (day 0 and 3). It should also be
noted that a schedule of 1 week would be preferable to the current schedule, because it
would be less time consuming, would improve compliance and gives less interference with the
intake of other prophylaxis measures, e. g. mefloquine. Two recent but small studies from
Thailand suggest that an accelerated schedule of three intradermal injections within 1 week
interval is as effective and immunogenic as administered within 4 weeks.
Therefore, this randomized, non-inferiority study will investigate whether the accelerated
schedule is as effective as the classical schedule. The investigators will also increase the
number of sites of injection, from one to two, to stimulate several different groups of
lymph nodes on the same time to initiate more antibody production.
Eligibility
Minimum age: 18 Years.
Maximum age: 47 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Willingness to provide written consent
- Seronegative for rabies
- Belgian soldiers who are deployable and visit the Travel clinic in Brussels during
their preparation phase before deployment OR military students at the schools of
Belgian Defense are eligible in preparation of an overseas exercise or during the
scheduled vaccination program at the end of their studies
- Prepared to follow the study schedule
Exclusion Criteria:
- Subjects who have had rabies vaccination (complete or incomplete) in the past due to
post-exposure prophylaxis.
- Subjects with a known allergy to one of the components of the vaccine.
- Immune depressed persons or intake of immunodepressant medication.
- Subjects who take mefloquine
- Planned deployment to overseas areas within 35 days.
Locations and Contacts
Military Hospital, Bruxelles B-1000, Belgium
Additional Information
Starting date: October 2011
Last updated: February 20, 2015
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