Ignite Creation Date:
2024-05-05 @ 11:53 AM
Last Modification Date:
2024-10-26 @ 9:15 AM
Study NCT ID:
NCT00168558
Status:
COMPLETED
Last Update Posted:
2012-03-06
First Post:
2005-09-09
Brief Title:
Early Two-dose Measles Vaccination Trial
Sponsor:
Bandim Health Project
Organization:
Bandim Health Project
Study Overview
Official Title:
Measles Vaccination in Guinea-Bissau Strategies to Reduce Disease Burden and Improve Child Survival
Status:
COMPLETED
Status Verified Date:
2012-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The specific aims are to examine in Guinea-Bissau
whether the standard titre Schwarz SW or standard-titre Edmonston-Zagreb EZ measles vaccine will be the best vaccine strain for use in a routine one-dose measles vaccination schedule and a two-dose measles vaccination schedule in terms of antibody response protection against measles and child survival and
whether the standard-titre Edmonston-Zagreb EZ vaccine will be suitable for use in a very early two-dose schedule vaccinating at 4½ and 9 months of age
whether the standard titre Schwarz SW or standard-titre Edmonston-Zagreb EZ measles vaccine will be the best vaccine strain for use in a routine one-dose measles vaccination schedule and a two-dose measles vaccination schedule in terms of antibody response protection against measles and child survival and
whether the standard-titre Edmonston-Zagreb EZ vaccine will be suitable for use in a very early two-dose schedule vaccinating at 4½ and 9 months of age
Detailed Description:
BACKGROUND
Two dose schedules
After the failure of the high-titre measles vaccine which was to be administered at 6 months of age it was suggested to perform trials of early two-dose measles vaccination schedules to lower the age of vaccination The standard titre SW measles vaccine has been shown to be associated with a non-specific beneficial effect on child mortality that cannot be ascribed to the protection against measles The two measles vaccines most commonly used in the Expanded Programme on Immunization EPI are the standard titre SW and the standard titre EZ vaccine Surprisingly these two vaccines have never been compared in a randomised trial with child mortality as end-point and it is not clear which would be most suitable for use in a two-dose vaccination schedule
From 1995 to 2002 all children in the BHP study area were included in an early two-dose measles vaccination trial from 6 months of age The children were randomised to either a one-dose group receiving an inactivated polio vaccine IPV at 6 months of age and a measles vaccine at 9 months of age or a two-dose group receiving two doses of measles vaccine at 6 and 9 months of age For the first 6 months of the trial the standard-titre EZ measles vaccine was used for the rest of the trial the standard-titre SW vaccine was used Results from the trial showed that an early two-dose schedule increased coverage considerably and provided better protection against measles among infants than the recommended one-dose at 9 months of age schedule The EZ and the SW vaccine were used in two different cohorts - so a direct comparison was not possible but the EZ vaccine seemed to boost a secondary immune response better than the SW vaccine Further the SW vaccine was less able to induce a protective level of antibodies when used from 6 months of age than the EZ vaccine The preliminary data that we have on long-term vaccine efficacy supports that the SW vaccine might be less suitable than the EZ vaccine for use in very early measles vaccine schedules unpublished data On the other hand trials performed during the 1980s in Mexico and Bangladesh have shown that administration of the standard-titre EZ vaccine to infants as young as 4-6 months of age gave good seroconversion results
The Global Measles Strategic Plan 2001-2005 developed by the WHO and UNICEF states that all children should be guaranteed a second opportunity for measles vaccination either through campaigns or routine immunisation The best strategy for protection of infants living in overcrowded urban African societies and who run a great risk of contracting measles before the recommended age of immunisation will probably be early vaccination followed by a second vaccination later in childhood If in a vaccination campaign strategy administration of the first vaccine is postponed this could dramatically increase the measles incidence in children below the age of vaccination To this add that vaccination campaigns have not yet been evaluated in Africa in terms of childhood mortality relative to the routine schedule Some children might get two three or even more measles vaccines in an uncontrolled and not necessarily beneficial manner Thus finding the best schedule and vaccine strain for use in a routine two-dose schedule seems a better approach for this region
We thus propose to conduct a study comparing the standard-titre SW measles vaccine and the standard-titre EZ measles vaccine in a one- or two-dose schedule providing the first dose at 9 months of age and then randomising the children at 18 months of age to receive either an additional dose of vaccine or nothing The groups will be compared in terms of seroconversion-rate proportion with an non-protective antibody level geometric mean titer antibody level vaccine efficacy and child mortality Further we plan to test the standard-titre EZ vaccine in a very early two-dose schedule providing the first dose at 4½ months of age and the second dose at 9 months of age see also non-specific effect of vaccination
It is likely that measles elimination vaccination campaigns will take place in the study area during the trial The date of vaccination and the type of measles vaccine used in such campaigns will be noted as well as simultaneous vitamin A supplementation and the information will be included in the final data-analyses
Non-specific effect of vaccination
The measles vaccine has in several community studies from different parts of the world been shown to have a non-specific beneficial effect on child mortality That means that the protection against death mediated by the vaccine exceeds the disease specific effect ie the vaccine not only prevents deaths caused by measles but also other deaths presumably due to a non-specific immune stimulation providing protection from other infections than measles For example during the war in Guinea-Bissau that broke out on June 7 1998 the population fled and the health care system broke down There was no routine vaccination for at least a 3 months period Hence when the war started there was a group of infants who had been randomised to early SW measles vaccination at 6 months or IPV and who did not receive the standard-titre SW measles vaccine at 9 month that they would otherwise have been given This natural experiment represents the first randomised study of the mortality effect of SW measles vaccine The mortality ratios for measles vaccinated children were 029 008-103 p0041 and 031 010-094 over the first 3 and 7 months of the war
Contrary to measles vaccination diphtheria-tetanus-pertussis DTP vaccination has been associated with a negative effect on child mortality Current studies indicate that the negative effect of DTP may be neutralized by a subsequent measles vaccination The design of the proposed trial will allow us to test whether the negative effect of the DTP vaccine which is administered by the EPI-programme at 6 10 and 14 weeks of age can be reverted by administration of a measles vaccine 4 weeks after the last DTP vaccination at around 4½ months of age
Non-specific effects of vaccination are sex-specific Girls benefit most from beneficial non-specific effects and suffer most from apparently harmful non-specific effects of vaccination Non-specific effects of measles vaccination may also show interaction with season the beneficial effect of measles vaccination being largest in the dry season unpublished suggesting that some unknown immunological factors play a role Season has a large influence on health in West Africa and both morbidity and mortality as well as immunologic parameters such as delayed-type hypersensitivity T-cells thymus size and measles antibody levels which are associated with season
We intend to investigate the interactions of sex and season with measles vaccination and will assure that data on morbidity and immunologic parameters will be collected both in the dry as well as in the rainy season
Time table
The study began in July 2003 and with a sample size of 5755 and a possible 2000 children included per year the inclusion period for the trial will be about 3 years
Two dose schedules
After the failure of the high-titre measles vaccine which was to be administered at 6 months of age it was suggested to perform trials of early two-dose measles vaccination schedules to lower the age of vaccination The standard titre SW measles vaccine has been shown to be associated with a non-specific beneficial effect on child mortality that cannot be ascribed to the protection against measles The two measles vaccines most commonly used in the Expanded Programme on Immunization EPI are the standard titre SW and the standard titre EZ vaccine Surprisingly these two vaccines have never been compared in a randomised trial with child mortality as end-point and it is not clear which would be most suitable for use in a two-dose vaccination schedule
From 1995 to 2002 all children in the BHP study area were included in an early two-dose measles vaccination trial from 6 months of age The children were randomised to either a one-dose group receiving an inactivated polio vaccine IPV at 6 months of age and a measles vaccine at 9 months of age or a two-dose group receiving two doses of measles vaccine at 6 and 9 months of age For the first 6 months of the trial the standard-titre EZ measles vaccine was used for the rest of the trial the standard-titre SW vaccine was used Results from the trial showed that an early two-dose schedule increased coverage considerably and provided better protection against measles among infants than the recommended one-dose at 9 months of age schedule The EZ and the SW vaccine were used in two different cohorts - so a direct comparison was not possible but the EZ vaccine seemed to boost a secondary immune response better than the SW vaccine Further the SW vaccine was less able to induce a protective level of antibodies when used from 6 months of age than the EZ vaccine The preliminary data that we have on long-term vaccine efficacy supports that the SW vaccine might be less suitable than the EZ vaccine for use in very early measles vaccine schedules unpublished data On the other hand trials performed during the 1980s in Mexico and Bangladesh have shown that administration of the standard-titre EZ vaccine to infants as young as 4-6 months of age gave good seroconversion results
The Global Measles Strategic Plan 2001-2005 developed by the WHO and UNICEF states that all children should be guaranteed a second opportunity for measles vaccination either through campaigns or routine immunisation The best strategy for protection of infants living in overcrowded urban African societies and who run a great risk of contracting measles before the recommended age of immunisation will probably be early vaccination followed by a second vaccination later in childhood If in a vaccination campaign strategy administration of the first vaccine is postponed this could dramatically increase the measles incidence in children below the age of vaccination To this add that vaccination campaigns have not yet been evaluated in Africa in terms of childhood mortality relative to the routine schedule Some children might get two three or even more measles vaccines in an uncontrolled and not necessarily beneficial manner Thus finding the best schedule and vaccine strain for use in a routine two-dose schedule seems a better approach for this region
We thus propose to conduct a study comparing the standard-titre SW measles vaccine and the standard-titre EZ measles vaccine in a one- or two-dose schedule providing the first dose at 9 months of age and then randomising the children at 18 months of age to receive either an additional dose of vaccine or nothing The groups will be compared in terms of seroconversion-rate proportion with an non-protective antibody level geometric mean titer antibody level vaccine efficacy and child mortality Further we plan to test the standard-titre EZ vaccine in a very early two-dose schedule providing the first dose at 4½ months of age and the second dose at 9 months of age see also non-specific effect of vaccination
It is likely that measles elimination vaccination campaigns will take place in the study area during the trial The date of vaccination and the type of measles vaccine used in such campaigns will be noted as well as simultaneous vitamin A supplementation and the information will be included in the final data-analyses
Non-specific effect of vaccination
The measles vaccine has in several community studies from different parts of the world been shown to have a non-specific beneficial effect on child mortality That means that the protection against death mediated by the vaccine exceeds the disease specific effect ie the vaccine not only prevents deaths caused by measles but also other deaths presumably due to a non-specific immune stimulation providing protection from other infections than measles For example during the war in Guinea-Bissau that broke out on June 7 1998 the population fled and the health care system broke down There was no routine vaccination for at least a 3 months period Hence when the war started there was a group of infants who had been randomised to early SW measles vaccination at 6 months or IPV and who did not receive the standard-titre SW measles vaccine at 9 month that they would otherwise have been given This natural experiment represents the first randomised study of the mortality effect of SW measles vaccine The mortality ratios for measles vaccinated children were 029 008-103 p0041 and 031 010-094 over the first 3 and 7 months of the war
Contrary to measles vaccination diphtheria-tetanus-pertussis DTP vaccination has been associated with a negative effect on child mortality Current studies indicate that the negative effect of DTP may be neutralized by a subsequent measles vaccination The design of the proposed trial will allow us to test whether the negative effect of the DTP vaccine which is administered by the EPI-programme at 6 10 and 14 weeks of age can be reverted by administration of a measles vaccine 4 weeks after the last DTP vaccination at around 4½ months of age
Non-specific effects of vaccination are sex-specific Girls benefit most from beneficial non-specific effects and suffer most from apparently harmful non-specific effects of vaccination Non-specific effects of measles vaccination may also show interaction with season the beneficial effect of measles vaccination being largest in the dry season unpublished suggesting that some unknown immunological factors play a role Season has a large influence on health in West Africa and both morbidity and mortality as well as immunologic parameters such as delayed-type hypersensitivity T-cells thymus size and measles antibody levels which are associated with season
We intend to investigate the interactions of sex and season with measles vaccination and will assure that data on morbidity and immunologic parameters will be collected both in the dry as well as in the rainy season
Time table
The study began in July 2003 and with a sample size of 5755 and a possible 2000 children included per year the inclusion period for the trial will be about 3 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| LÆGEVIDENSKABENS FREMME-2623 | None | None | None |
| RUF-91134-2601 | None | None | None |
| NOVO-2624 | None | None | None |
| LÆGEVIDENSKABENS FREMME-2613 | None | None | None |