Severe IllnessPhase 3NCT02606526
Early Versus Late BCG Vaccination in HIV-1 Exposed Infants in Uganda in Uganda
A Phase 3 study testing BCG at birth in people with Severe Illness and Septicaemia, run by Makerere University at 1 site in Uganda.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 1 dayHealthy volunteers can take part
- Conditions the study is for
- Severe Illness, Septicaemia, Diarrhoea
- What is being tested?
- BCG at birth
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4,500 participants
- Where
- 1 siteUganda
- Study dates
- Jul 2016to 21 Jun 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 1 day
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- a severely ill mother with (a) condition(s) requiring hospitalization
- a baby with an Apgar score at 5 minutes <7
- a twin or triplet
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised Controlled Trial in HIV-1 Exposed Ugandan Infants to Estimate Additional Benefits (Non-specific Effects) of BCG
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.
Read more
The main study outcomes include:
- Severe illness in the first 14 weeks of life,
- Innate and adaptive immune responses to mycobacterial, non-mycobacterial antigens and TLR-agonists
- Severe illness in the first 14-52 weeks and 0-52 weeks of life.
The study will be carried in two health centers and one district hospital 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.
- Conditions
- Severe Illness, Septicaemia, Diarrhoea, Lower Respiratory Infection
- Being tested
- BCG at birth, Control arm: Delayed BCG
- Medical subject headings
- Toxemia, Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCG at birthBiological
See previous description
Control arm: Delayed BCGBiological
See previous description
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Biological: Control arm: Delayed BCG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 14 weeks post BCG vaccination
Secondary outcomes (8)
Severe illness from 48 h after randomization to 14 weeks of life
Severe illness as defined for primary outcome 1
Measured: 48 hours to 14 weeks of life
Severe illness in weeks 0-52 and 14-52 of life
Severe illness as defined for primary outcome 1
Measured: First 0-52 and 14-52 weeks of life
Adverse events
Axillary and cervical lymphadenopathy
Measured: First 52 weeks of life
Infant death
Death during the first year of life
Measured: First year of life
BCG scar at 52 weeks of age
Presence or absence of a BCG scar at the vaccination site
Measured: First year of life
Growth up to 52 weeks of life
Growth measured by weight and length
Measured: First year of life
Severe illness until 6 weeks of age
Severe illness as defined for primary outcome 1
Measured: 6 weeks
Severe illness until 14 weeks of age within strata of presence or absence of maternal BCG scar
In addition to the above-mentioned outcomes, an analysis plan will be developed which may include any necessary new or modifications in the current secondary outcomes and describe any new secondary analyses, including for sub-group effects".
Measured: 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2015 (estimated)
- Study startJul 2016
- Primary completion21 Jun 2024
- Study completion21 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Severe IllnessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 4,500 participants (actual)
Sponsor and investigators
- Lead sponsor
- Makerere University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Bergen, Radboud University Medical Center
- Responsible party
- Sponsor
- Investigators
- Victoria Nankabirwa, MD, MPH, PhD, Principal investigator, School of Public Health, Makerere UniversityHalvor Sommerfelt, MD, PhD, Principal investigator, CISMAC, Center for International Health, University of Bergen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02606526
- Sponsor's protocol ID
- 2015-114
- Status last verified
- Feb 2025
- First submitted
- 12 Nov 2015
- Last updated
- 4 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 25886062Nankabirwa 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.
PubMed 28359325
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Controlled Trial in HIV-1 Exposed Ugandan Infants to Estimate Additional Benefits (Non-specific Effects) of BCG
- ClinicalTrials.gov ID
- NCT02606526
- Acronym / sponsor ID
- 2015-114
- Conditions
- Severe Illness, Septicaemia, Diarrhoea, Lower Respiratory Infection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4,500 participants (actual)
- Lead sponsor
- Makerere UniversityUniversity, hospital or other
- Collaborators
- University of Bergen, Radboud University Medical Center
- Study start
- Jul 2016 (actual)
- Primary completion
- 21 Jun 2024 (actual)
- Study completion
- 21 Jun 2024 (actual)
- First posted
- 17 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Severe illness in the first 14 weeks of life,
- Innate and adaptive immune responses to mycobacterial, non-mycobacterial antigens and TLR-agonists
- Severe illness in the first 14-52 weeks and 0-52 weeks of life.
The study will be carried in two health centers and one district hospital 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention arm: BCG at birth | Experimental | Biological: BCG at birthInfants randomized to this arm will receive an intra-dermal administration of 0.05 ml of BCG vaccine within 24h of birth |
| Control arm: BCG at 14 weeks of age | Active comparator | Biological: Control arm: Delayed BCGInfants randomized to this arm will receive intra-dermal administration of 0.05 ml of BCG vaccine at 14 weeks of age |
Who may qualify
- Ages
- Up to 1 day
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BCG at birthSee previous description | Biological | Intervention arm: BCG at birth |
| Control arm: Delayed BCGSee previous description | Biological | Control arm: BCG at 14 weeks of age |
Primary outcome
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 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.
Innate and adaptive immune responses against mycobacterial and non-mycobacterial antigens.
Time frame: 14 weeks post BCG vaccination
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).
8 secondary outcomes
Severe illness from 48 h after randomization to 14 weeks of life
Time frame: 48 hours to 14 weeks of life
Severe illness in weeks 0-52 and 14-52 of life
Time frame: First 0-52 and 14-52 weeks of life
Adverse events
Time frame: First 52 weeks of life
Infant death
Time frame: First year of life
BCG scar at 52 weeks of age
Time frame: First year of life
Growth up to 52 weeks of life
Time frame: First year of life
Severe illness until 6 weeks of age
Time frame: 6 weeks
Severe illness until 14 weeks of age within strata of presence or absence of maternal BCG scar
Time frame: 14 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2025.
- Background: PubMed 25886062Nankabirwa 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.
- Background: PubMed 28359325Nankabirwa 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Victoria Nankabirwa, MD, MPH, PhD principal investigator
School of Public Health, Makerere University
Halvor Sommerfelt, MD, PhD principal investigator
CISMAC, Center for International Health, University of Bergen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BCG at birth in people with Severe Illness and Septicaemia, run by Makerere University at 1 site in Uganda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Severe illness (time frame: The first 14 weeks of life). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02606526, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2025.