Early Versus Late BCG Vaccination in HIV-1 Exposed Infants in Uganda in Uganda

NCT02606526 | Completed Phase 3 DMC

• 1 other identifier: 2015-114
• Study Type: interventional
• Target: 4,500
• Locations: 1 country
• Sites: 1

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:

1. 1.Severe illness in the first 14 weeks of life,
2. 2.Innate and adaptive immune responses to mycobacterial, non-mycobacterial antigens and TLR-agonists
3. 3.Severe illness in the first 14-52 weeks and 0-52 weeks of life.

Conditions

Severe Illness; Septicaemia; Diarrhoea; Lower Respiratory Infection

Outcome Measures

Primary Outcomes (2)

• Severe illness

  Among children \<2 months of age, severe illness (other than TB) will be defined as an acute 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 ≥38.0 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 an acute 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 are not considered severe illness.

  The first 14 weeks of life

• Innate and adaptive immune responses against mycobacterial and non-mycobacterial antigens.

  The following immunological outcomes will be measured in a sub-sample of 180 infants: Innate immune responses (IL-6, TNF, IL-10, IL-1b) against TLR-agonists and adaptive immune responses (IFNy, IL-17, IL-10 and IL-22) against mycobacterial (ESAT-6/CFT10 and PPD) and non-mycobacterial antigens (C.albicans, S. aureus and SARS-CoV-2 spike peptides).

  14 weeks post BCG vaccination

Secondary Outcomes (8)

• Severe illness from 48 h after randomization to 14 weeks of life

  48 hours to 14 weeks of life

• Severe illness in weeks 0-52 and 14-52 of life

  First 0-52 and 14-52 weeks of life

• Adverse events

  First 52 weeks of life

• Infant death

  First year of life

• BCG scar at 52 weeks of age

  First year of life

Study Arms (2)

Intervention arm: BCG at birth

EXPERIMENTAL

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

Control arm: BCG at 14 weeks of age

ACTIVE COMPARATOR

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

Interventions

BCG at birth BIOLOGICAL

See previous description

Intervention arm: BCG at birth

Control arm: Delayed BCG BIOLOGICAL

See previous description

Control arm: BCG at 14 weeks of age

Eligibility Criteria

• Age: Up to 1 Day
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• A baby born at a participating study clinic will be included if s/he:
• has a mother with a positive HIV test (ELISA or rapid test)
• is receiving peri-exposure prophylaxis as part of the standard/national guidelines in Uganda
• has a mother that is of legal age for participation in clinical research studies in Uganda or is an emancipated minor
• 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
• has a mother/caregiver that gives informed consent to random assignment to either of the two trial arms
• has a mother that has received antiretroviral therapy (ART) for at least 4 weeks

You may not qualify if:

• A new-born child will be excluded if she/he has:
• an identified serious congenital malformation(s)
• severe illness requiring hospitalization
• a birth weight \< 2.0 kg
• 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.
• a mother or other household member with symptoms and signs of tuberculosis on the day of enrolment
• a severely ill mother with (a) condition(s) requiring hospitalization
• a baby with an Apgar score at 5 minutes \<7
• a twin or triplet

Sponsors & Collaborators

• Makerere University: lead
• University of Bergen: collaborator
• Radboud University Medical Center: collaborator

Study Sites (1)

Health Centers in Mukono and Kampala districts

Kampala, Uganda

Location

Related Publications (2)

• Nankabirwa V, Tumwine JK, Mugaba PM, Tylleskar T, Sommerfelt H; PROMISE- EBF Study Group. Child survival and BCG vaccination: a community based prospective cohort study in Uganda. BMC Public Health. 2015 Feb 22;15:175. doi: 10.1186/s12889-015-1497-8.

  PMID: 25886062 BACKGROUND

• Nankabirwa V, Tumwine JK, Namugga O, Tylleskar T, Ndeezi G, Robberstad B, Netea MG, Sommerfelt H. Early versus late BCG vaccination in HIV-1-exposed infants in Uganda: study protocol for a randomized controlled trial. Trials. 2017 Mar 31;18(1):152. doi: 10.1186/s13063-017-1881-z.

  PMID: 28359325 BACKGROUND

MeSH Terms

Conditions

Toxemia; Diarrhea

Condition Hierarchy (Ancestors)

Infections; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Victoria Nankabirwa, MD, MPH, PhD

  School of Public Health, Makerere University

  PRINCIPAL INVESTIGATOR

• Halvor Sommerfelt, MD, PhD

  CISMAC, Center for International Health, University of Bergen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2015
• First Posted: November 17, 2015
• Study Start: July 1, 2016
• Primary Completion: June 21, 2024
• Study Completion: June 21, 2024
• Last Updated: March 4, 2025

Record last verified: 2025-02

Locations

UG (1)