Early Versus Late BCG Vaccination in HIV-1 Exposed Infants in Uganda in Uganda
Study Details
Study Description
Brief Summary
BCG vaccination may have non-specific effects (NSE) i.e., additional benefits on childhood morbidity and mortality that are separate the vaccine's effect on the incidence of disseminated tuberculosis. Though the available literature is mostly from observational study designs, and is fraught with controversy, BCG vaccination at birth, in a high risk population of HIV exposed children, may protect infants against serious infections other than TB. Yet, other studies indicate that giving BCG later in infancy, when the immune system is more mature, may offer even greater protection. The appropriate timing of BCG vaccination could therefore be up for revision. This study will therefore compare BCG vaccination at birth with BCG vaccination at 14 weeks of age in HIV exposed (HE) babies.
Methods: This is an individually randomized clinical trial in 4,500 HIV exposed infants. The intervention is an intra-dermal administration of 0.05 ml of BCG vaccine within 24 hours of birth while the comparator will be an intra-dermal administration of 0.05ml of BCG vaccine at 14 weeks of age.
The main study outcomes include:
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Severe illness in the first 14 weeks of life,
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TNF, IL-1b, IL-6 and IFN-γ in response to mycobacterial and non-mycobacterial antigens and
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Severe illness in the first 14-52 weeks and 0-52 weeks of life.
The study will be carried in two health Center IIIs and a health center IV in Uganda.
Implications: A well-timed BCG vaccination could have important additional benefits in HE infants. This trial could inform the development of programmatically appropriate timing of BCG vaccination for HE infants.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Intervention arm: BCG at birth Infants randomized to this arm will receive an intra-dermal administration of 0.05 ml of BCG vaccine within 24h of birth |
Biological: BCG at birth
See previous description
|
| Active Comparator: Control arm: BCG at 14 weeks of age Infants randomized to this arm will receive intra-dermal administration of 0.05 ml of BCG vaccine at 14 weeks of age |
Biological: Control arm: Delayed BCG
See previous description
|
Outcome Measures
Primary Outcome Measures
- Proportion of infants with severe illness [The first 14 weeks of life]
Among children <2 months of age, severe illness (other than TB) will be defined as illness that is associated with any of the following danger signs observed or verified by a clinician: inability to feed or vomiting of everything and unable to keep anything down, lethargy or unconsciousness, severe lower chest in-drawing, axillary temperature of ≥37.5 deg C or <35.5 deg C, grunting, cyanosis, convulsions or a history of convulsions (except epilepsy), and/or requires hospitalization and/or results in death. Among children ≥2 months of age, severe illness (other than TB) will be defined as illness that is associated with at least one of the following danger signs observed by a clinician: inability to drink or breastfeed lethargy or unconsciousness, vomiting of all feeds, convulsions or a history of convulsions (except epilepsy), and/or requires hospitalization and/or results in death. Events resulting from violent injury or burns will not be considered.
- Production of TNF, IL-1beta, IL-6 and IFN-γ in response to mycobacterial (from M. tuberculosis and PPD) and non-mycobacterial antigens (from E. coli, C.albicans and S. aureus) [14 weeks post BCG vaccination]
Secondary Outcome Measures
- Proportion of infants with severe illness from 48 h after randomization to 14 weeks of life [48 hours to 14 weeks of life]
- Proportion of infants with severe illness in the first 14-52 weeks and 0-52 weeks of life [First 14-52 weeks and 0-52 weeks of life]
Among children <2 months of age, severe illness (other than TB) will be defined as illness that is associated with any of the following danger signs observed or verified by a clinician: inability to feed or vomiting of everything and unable to keep anything down, lethargy or unconsciousness, severe lower chest in-drawing, axillary temperature of ≥37.5 deg C or <35.5 deg C, grunting, cyanosis, convulsions or a history of convulsions (except epilepsy), and/or requires hospitalization and/or results in death. Among children ≥2 months of age, severe illness (other than TB) will be defined as illness that is associated with at least one of the following danger signs observed by a clinician: inability to drink or breastfeed lethargy or unconsciousness, vomiting of all feeds, convulsions or a history of convulsions (except epilepsy), and/or requires hospitalization and/or results in death. Events resulting from violent injury or burns will not be considered.
- Adverse events [First 52 weeks of life]
- Infant death [First year of life]
- Proportion of infants with BCG scarring [12 weeks post vaccination]
Presence or absence of a BCG scar at the vaccination site
- Growth up to 52 weeks of life [First year of life]
- Severe illness until 6 weeks of age [6 weeks]
- Severe illness until 14 weeks of age within strata of presence or absence of maternal BCG scar [14 weeks]
Eligibility Criteria
Criteria
Inclusion Criteria:
A baby born at a participating study clinic will be included if s/he:
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has a mother with a positive HIV test (ELISA or rapid test)
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is receiving peri-exposure prophylaxis as part of the standard/national guidelines in Uganda
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has a mother that is of legal age for participation in clinical research studies in Uganda or is an emancipated minor
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has a mother/caregiver that resides within the study area, is not intending to move out of the area in the next 4 months and is likely to be traceable for up to 12 months
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has a mother/caregiver that gives informed consent to random assignment to either of the two trial arms
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has a mother that has received antiretroviral therapy (ART) for at least 4 weeks
Exclusion Criteria:
A new-born child will be excluded if she/he has:
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serious congenital malformation(s)
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severe illness requiring hospitalization
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a birth weight < 2.0 kg
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a mother participating in another clinical trial on the day of enrolment or a mother who will participate in another clinical trial within the next month.
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a mother or other household member with symptoms and signs of tuberculosis on the day of enrolment
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a severely ill mother with (a) condition(s) requiring hospitalization
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a baby with an Apgar score at 5 minutes <7
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a twin or triplet
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Health Centers in Mukono and Kampala districts | Kampala | Uganda |
Sponsors and Collaborators
- Makerere University
- Centre For International Health
- Radboud University Medical Center
Investigators
- Principal Investigator: Victoria Nankabirwa, MD, MPH, PhD, Department of Epidemiology and Biostatistics, School of Public Health, College of Health Sciences, Makerere University
- Principal Investigator: Halvor Sommerfelt, MD, PhD, CISMAC, Center forInternational Health, University of Bergen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- 2015-114