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

This study is currently recruiting participants.
See Contacts and Locations
Verified November 2016 by Makerere University
Sponsor:
Collaborators:
Centre For International Health
Radboud University
Information provided by (Responsible Party):
Makerere University
ClinicalTrials.gov Identifier:
NCT02606526
First received: November 12, 2015
Last updated: November 25, 2016
Last verified: November 2016
  Purpose

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 2,200 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. Severe illness in the first 14 weeks of life,
  2. TNF, IL‑1b, IL-6 and IFN-γ in response to mycobacterial and non-mycobacterial antigens and
  3. 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 Intervention Phase
Severe Illness Septicaemia Diarrhoea Malaria Lower Respiratory Infection Biological: BCG at birth Biological: Control arm: Delayed BCG Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Randomised Controlled Trial in HIV-1 Exposed Ugandan Infants to Estimate Additional Benefits (Non-specific Effects) of BCG

Resource links provided by NLM:


Further study details as provided by Makerere University:

Primary Outcome Measures:
  • Proportion of infants with severe illness [ Time Frame: 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 study 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, and/or results in 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, and/or results in hospitalization and/or results in death. Hospitalization and death resulting from violent injury or burns will not contribute to the severe illness definition.

  • 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) [ Time Frame: 14 weeks post BCG vaccination ]

Secondary Outcome Measures:
  • Proportion of infants with severe illness from 48 h after randomization to 14 weeks of life [ Time Frame: 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 [ Time Frame: 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 study 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, and/or results in 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, and/or results in hospitalization and/or results in death. Hospitalization and death resulting from violent injury or burns will not contribute to the severe illness definition.

  • Adverse events [ Time Frame: First 52 weeks of life ]
  • Infant death [ Time Frame: First year of life ]
  • Proportion of infants with BCG scarring [ Time Frame: 12 weeks post vaccination ]
    Presence or absence of a BCG scar at the vaccination site

  • Growth up to 52 weeks of life [ Time Frame: First year of life ]

Estimated Enrollment: 2200
Study Start Date: July 2016
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   up to 1 Day   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

A baby born at a participating study clinic will be included if s/he:

  1. has a mother with a positive HIV test (ELISA or rapid test)
  2. is receiving peri-exposure prophylaxis as part of the standard/national guidelines in Uganda
  3. has a mother that is of legal age for participation in clinical research studies in Uganda or is an emancipated minor
  4. 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
  5. has a mother/caregiver that gives informed consent to random assignment to either of the two trial arms
  6. 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:

  1. serious congenital malformation(s)
  2. severe illness requiring hospitalization
  3. a birth weight < 2.0 kg
  4. 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.
  5. a mother or other household member with symptoms and signs of tuberculosis on the day of enrolment
  6. a severely ill mother with (a) condition(s) requiring hospitalization
  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: NCT02606526

Contacts
Contact: Victoria Nankabirwa, MD, MPH, PhD +256755757460 nankabirwav@gmail.com
Contact: Olive Namugga, MD +256790515426 olivedejackie@yahoo.com

Locations
Uganda
Health Centers in Mukono and Kampala districts Recruiting
Kampala, Uganda
Contact: Victoria Nankabirwa, MBChB, MPH, PhD    +256755757460    nankabirwav@gmail.com   
Contact: Olive Namugga, MBChB, MPH    070065949    olivedejackie@yahoo.com   
Principal Investigator: Victoria Nankabirwa, PhD         
Principal Investigator: Halvor Sommerfelt, PhD         
Sub-Investigator: Grace Ndeezi, PhD         
Sub-Investigator: James Tumwine, PhD         
Sub-Investigator: Bjarne Robberstad, PhD         
Sub-Investigator: Mihai Netea, PhD         
Sub-Investigator: Thorkild Tylleskar, PhD         
Sponsors and Collaborators
Makerere University
Centre For International Health
Radboud University
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
  More Information

Additional Information:
Publications:
Responsible Party: Makerere University
ClinicalTrials.gov Identifier: NCT02606526     History of Changes
Other Study ID Numbers: 2015-114
Study First Received: November 12, 2015
Last Updated: November 25, 2016

Additional relevant MeSH terms:
Diarrhea
Respiratory Tract Infections
Sepsis
Signs and Symptoms, Digestive
Signs and Symptoms
Infection
Respiratory Tract Diseases
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes

ClinicalTrials.gov processed this record on August 18, 2017