Clinical Trial: Simplifying the Rabies Pre-exposure Vaccination

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Simplifying the Rabies Pre-exposure Vaccination

Brief 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

Detailed Summary:

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 repre
Sponsor: Institute of Tropical Medicine, Belgium

Current Primary Outcome: Boostability of the rabies antibodies [ Time Frame: Day 7 after booster vaccination ]

The primary endpoint is the boostability of the rabies antibodies on day 7 after booster vaccination, carried out at years 1 to 3 after initial vaccination. A rabies serology value of more than 0,5 IU/ml (international unit/milliliter) on day 7 after booster vaccination is considered to be protective. Subjects showing this serology value at day 7 are considered to be boostable.


Original Primary Outcome: Boostability of the rabies antibodies [ Time Frame: Day 7 after booster vaccination ]

The primary endpoint is the boostability of the rabies antibodies on day 7 after booster vaccination, carried out at years 1 to 3 after initial vaccination. A rabies serology value of more than 0,5 IU/ml on day 7 after booster vaccination is considered to be protective. Subjects showing this serology value at day 7 are considered to be boostable.


Current Secondary Outcome:

  • Rabies serology [ Time Frame: Day 35 after primary (initial) vaccination ]
    Rabies serology more than 0,5 IU/ml on day 35 after primary vaccination.
  • Rabies serology [ Time Frame: Day 35 after primary (initial) vaccination, and after booster vaccination ]
    Rabies serology more than 10 IU/ml on day 35 after primary vaccination, and after booster vaccination.
  • Serological response of booster vaccinations [ Time Frame: Day 7 after booster vaccination ]
    Serological response of booster vaccinations for non- or hypo-responders in both arms.
  • Adverse events [ Time Frame: One week after initial and booster vaccination ]
    Adverse events within one week after initial and booster vaccinations
  • Serious adverse events [ Time Frame: 28 days after initial and booster vaccination ]
    Serious adverse event within 28 days after initial and booster vaccinations


Original Secondary Outcome: Same as current

Information By: Institute of Tropical Medicine, Belgium

Dates:
Date Received: July 5, 2011
Date Started: October 2011
Date Completion:
Last Updated: March 4, 2016
Last Verified: March 2016