Randomized Study of Not Giving Diphteria-tetanus-pertussis Vaccination With or After Measles Vaccination

This study has been completed.
Sponsor:
Collaborators:
Aarhus University Hospital
Rigshospitalet, Denmark
Information provided by (Responsible Party):
Bandim Health Project
ClinicalTrials.gov Identifier:
NCT00244673
First received: October 25, 2005
Last updated: February 25, 2012
Last verified: February 2012
  Purpose

In non-randomized studies, routine childhood vaccinations have been observed to have non-targeted effects. Difteria-tetanus-pertussis (DTP) vaccine provided with or after measles vaccine (MV) is associated with increased mortality in areas with herd immunity to pertussis.

We will examine in a randomised study of 6000 children the effect of not administering DTP simultaneously with or after MV on overall child mortality, hospitalization rates, and the immunological responses after vaccination. We will also examine potential sex-differential effects in the outcomes and interactions with other vaccines, other health interventions and season.


Condition Intervention Phase
Mortality
Hospitalization
Adverse Events
Biological: DTP3/4+OPV+MV versus OPV+MV or DTP4+OPV4 versus OPV4
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Diphteria-tetanus-pertussis (DTP) Vaccination and Child Survival: Randomized Study of Not Providing DTP Vaccination Together With or After Measles Vaccination

Resource links provided by NLM:


Further study details as provided by Bandim Health Project:

Primary Outcome Measures:
  • Mortality till 4 years of age [ Time Frame: June 2011 ] [ Designated as safety issue: Yes ]
  • Hospitalisations till 4 years of age [ Time Frame: June 2011 ] [ Designated as safety issue: Yes ]
  • Adverse events 1 month after intervention [ Time Frame: December 2008 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Immunological responses [ Time Frame: July 2008 ] [ Designated as safety issue: Yes ]
  • Morbidity [ Time Frame: June 2011 ] [ Designated as safety issue: Yes ]

Enrollment: 6534
Study Start Date: October 2005
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: DTP3/4+OPV+MV versus OPV+MV or DTP4+OPV4 versus OPV4
    Trial of not providing 3. and/or 4. DTP together with or after MV at 9 to 18 month of age.
Detailed Description:

Background: Infectious diseases are the main cause of high child mortality in Africa. In several non-randomised studies, routine childhood vaccinations have been observed to have non-targeted effects. Live vaccines like measles vaccine (MV) seem to protect against overall mortality, whereas killed vaccines, like DTP, may have no beneficial effects, especially for girls. DTP provided with or after MV may be associated with increased mortality. The mechanisms behind these effects are unknown.

Hypothesis: Not providing DTP together with or after MV is associated with a 35 % reduction in overall mortality and 23% reduction in hospitalizations.

Objectives: To examine in a randomised study of 6000 children the effect of not administering DTP simultaneously with or after MV on

  1. Overall child mortality
  2. Hospitalization rates and major causes of hospitalization
  3. The immunological profile after vaccination
  4. Sex-differences in the above mentioned outcomes

Methods:

Surveillance system: BHP's demographic surveillance system in Bissau covers 6 districts with a population of 90,000; 3,500 children are born each year.

Hospitalizations: There is only one pediatric ward in Bissau and all hospitalizations are identified in the BHP register.

Vaccinations: Vaccinations are provided and registered at the 3 health centres in the study area.

Intervention: In this study 6000 children are randomised as they come to receive DTP3 or DTP booster with or after measles vaccination (MV) at the local health centres. Children will be randomised to DTP3+OPV3 and MV versus OPV3 and MV or DTP4+OPV4 versus OPV4 (booster doses).

Follow-up: The children will be followed until 4 years of age or end of study.

  1. Adverse effects: In the first month after vaccination, 1000 children will be visited daily for three days and then weekly to register morbidity and consultations.
  2. Hospitalizations: The children will be followed at the pediatric ward.
  3. Mortality: Children will be followed by the routine surveillance system. Furthermore, all children will be visited yearly and finally when they reach four years of age. When a death is detected, a physician will conduct a verbal autopsy.

Sample size: With a total of 7500 person-years of follow-up, we will be able to document a 35% reduction in mortality and a 23% reduction in hospitalizations. A subgroup of children will be examined for possible differences in immunological profile after vaccination.

Ethical considerations: Herd immunity to pertussis should not be affected as, due to the intervention, more children is vaccinated.

  Eligibility

Ages Eligible for Study:   9 Months to 4 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The child should be missing DTP3 or DTP4
  2. The child should have received DTP2
  3. The child should have received MV already or receive MV on the day of enrolment

Exclusion Criteria:

Normally applied contraindications for receiving vaccinations, including high fever

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00244673

Locations
Guinea-Bissau
Bandim Health Project, Apartado 861
Bissau, Guinea-Bissau
Sponsors and Collaborators
Bandim Health Project
Aarhus University Hospital
Rigshospitalet, Denmark
Investigators
Principal Investigator: Peter Aaby, DMSc Bandim Health Project
  More Information

No publications provided

Responsible Party: Bandim Health Project
ClinicalTrials.gov Identifier: NCT00244673     History of Changes
Other Study ID Numbers: CVEK2005-7041-45-DTPMV, CVEK2005-7041-45
Study First Received: October 25, 2005
Last Updated: February 25, 2012
Health Authority: Guinea-Bissau: Ministry of Health

Keywords provided by Bandim Health Project:
Vaccination
DTP
Child mortality
Sex
Non-specific effects

Additional relevant MeSH terms:
Diphtheria
Measles
Whooping Cough
Tetanus
Corynebacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Morbillivirus Infections
Paramyxoviridae Infections
Mononegavirales Infections
RNA Virus Infections
Virus Diseases
Bordetella Infections
Gram-Negative Bacterial Infections
Respiratory Tract Infections
Infection
Respiratory Tract Diseases
Clostridium Infections

ClinicalTrials.gov processed this record on July 22, 2014