Neonatal SepsisPhase 3ProRIDENCT04172012
Use of Probiotics to Reduce Infections, Death and ESBL Colonisation
A Phase 3 study testing Labinic (R) probiotic mixture in people with Neonatal Sepsis, run by Haydom Lutheran Hospital at 1 site in Tanzania.
Trial summary
This study examines the effect of oral probiotic treatment to newborns on preventing hospitalizations, death and colonization with Extended-spectrum beta-lactamase-producing Gram negative bacteria. Read more about this study
- Who is it for?
- Ages Up to 3 daysHealthy volunteers can take part
- Conditions the study is for
- Neonatal Sepsis
- What is being tested?
- Labinic (R) probiotic mixture
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,000 participants
- Where
- 1 siteTanzania
- Study dates
- 1 Feb 2022to 19 Sep 2023
- 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 3 days
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Healthy newborn infants with a birth weight equal or above 2.0 kgs, will be included in the study between 0-3 days of life.
- Newborn infants have to come from families who are long-term or permanent residents in the defined catchment area for this trial (30 km radius from HLH) in Tanzania.
- Parents are able and willing to complete study visit (including required study procedures) schedules over the six months proposed follow-up, which also includes hospitalizations required for compliance of this study protocol.
- Parents agrees for the child not to participate in another study during the study period
- Children less than one year admitted to hospital with suspected infection, not included in the RCT, will be included in a sub-study. A separate inclusion form is prepared for these children.
Who cannot join
- Birth weight below 2 kg
- Other health problems/illness, obvious congenital malformations.
- Multiple pregnancy
- Parents not consenting
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Use of Probiotics to Reduce Infections and Death and Prevent Colonization With Extended-spectrum Beta-lactamase Producing Bacteria, Among Newborn Infants in Haydom and Surrounding Area, Tanzania, a Randomized Controlled Clinical Trial
This study examines the effect of oral probiotic treatment to newborns on preventing hospitalizations, death and colonization with Extended-spectrum beta-lactamase-producing Gram negative bacteria. Half of the babies will receive 4 weeks treatment with an oral mixture of the probiotic Labinic (R) while the other half will receive a placebo mixture.
Read the detailed description
Studies show that probiotics given to prematurely born babies prevents sepsis and is widely used in the western world for this purpose. Probiotics consists of one or more normal gut-bacteria. A large study in India showed that giving probiotics to full-born babies reduced hospitalizations and morbidity. This study investigates giving a probiotic mixture with different combination of bacteria, Lactobacillus acidophilus, Bifidobacterium infantis and Bifidobacterium breve, for a longer duration (4 weeks instead of 7 days).
Infections with antibiotic-resistant bacteria is a major threat to health-care world-wide, and sepsis/severe infection caused by such bacteria is a major cause of neonatal death. The study hypothesis is that giving probiotics to newborns prevents them from getting colonized with antibiotic-resistant bacteria, such as Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). By preventing colonization with ESBL-PE, severe infections such as sepsis may be prevented, and thereby survival may be improved.
- Conditions
- Neonatal Sepsis
- Being tested
- Labinic (R) probiotic mixture, Placebo
- Keywords
- Tanzania, East Africa, Antimicrobial resistance, Probiotics, Extended Spectrum Beta-Lactamase Producing Bacteria
- Medical subject headings
- Neonatal Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Labinic (R) probiotic mixtureBiological
Labinic (R) probiotic mixture containing Lactobacillus acidophilus and Bifidobacterium infantis and B. breve
PlaceboOther
Placebo mixture
| Study group | Role | What they receive |
|---|---|---|
| Probiotic | Active comparator | Study subjects receive probiotic mixture for 4 weeks Receives: Biological: Labinic (R) probiotic mixture |
| Placebo | Placebo comparator | Study subjects receive placebo mixture for 4 weeks Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite outcome hospitalization and death
Primary outcome is hospitalization and/or death of study subject
Measured: 6 months from inclusion
Secondary outcomes (12)
ESBL colonization
Faecal colonisation with Extended-spectrum beta-lactamase-producing Enterobacteriaceae as detected by fecal swab
Measured: 6 weeks and 6 months
Hospitalisation
Hospitalisation
Measured: 6 weeks and 6 months
Death
Death during study period
Measured: 6 months
Body weight
Growth monitored by weight
Measured: 6 months
Body length
Growth monitored by length
Measured: 6 months
Stool microbiota
Stool microbiota composition including resistome analysis (metagenome sequencing)
Measured: 6 weeks and 6 months
Stool metabolome
Stool metabolome composition
Measured: 6 weeks and 6 months
Stool inflammatory markers - Calprotectin
Levels of Calprotectin in participants' stool samples
Measured: 6 weeks and 6 months
Stool inflammatory markers - alpha-1 antitrypsin
Levels of alpha-1 antitrypsin (AAT) in participants' stool samples
Measured: 6 weeks and 6 months
Stool inflammatory markers - myeloperoxidase
Levels of human myeloperoxidase (MPO) in participants' stool samples
Measured: 6 weeks and 6 months
Number of participants with culture-confirmed bacteremia
Bacteremia confirmed by blood culture
Measured: 6 months
Genetic characteristics of ESBL-producing Enterobacteriaceae
Genetic characteristics of ESBL-E from colonization and clinical samples (targeted screening)
Measured: 6 weeks and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2019
- Study start1 Feb 2022
- Primary completion10 Jul 2023
- Study completion19 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Neonatal SepsisStudies 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
- Model description
- Placebo-controlled double-blinded randomized clinical trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- Haydom Lutheran Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Bergen, Helse Stavanger HF, UiT The Arctic University of Norway, Muhimbili University of Health and Allied Sciences
- Responsible party
- Sponsor
- Investigators
- Nina Langeland, MD, PhD, Principal investigator, University of Bergen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04172012
- Sponsor's protocol ID
- 2019/1025
- Acronym
- ProRIDE
- Status last verified
- Apr 2025
- First submitted
- 19 Nov 2019
- Last updated
- 25 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Panigrahi P, Parida S, Nanda NC, Satpathy R, Pradhan L, Chandel DS, Baccaglini L, Mohapatra A, Mohapatra SS, Misra PR, Chaudhry R, Chen HH, Johnson JA, Morris JG, Paneth N, Gewolb IH. A randomized synbiotic trial to prevent sepsis among infants in rural India. Nature. 2017 Aug 24;548(7668):407-412. doi: 10.1038/nature23480. Epub 2017 Aug 16.
PubMed 28813414Esaiassen E, Hjerde E, Cavanagh JP, Pedersen T, Andresen JH, Rettedal SI, Stoen R, Nakstad B, Willassen NP, Klingenberg C. Effects of Probiotic Supplementation on the Gut Microbiota and Antibiotic Resistome Development in Preterm Infants. Front Pediatr. 2018 Nov 16;6:347. doi: 10.3389/fped.2018.00347. eCollection 2018.
PubMed 30505830Tellevik MG, Blomberg B, Kommedal O, Maselle SY, Langeland N, Moyo SJ. High Prevalence of Faecal Carriage of ESBL-Producing Enterobacteriaceae among Children in Dar es Salaam, Tanzania. PLoS One. 2016 Dec 9;11(12):e0168024. doi: 10.1371/journal.pone.0168024. eCollection 2016.
PubMed 27936054Moyo SJ, Justine M, Blomberg B, Lohr IH, Gideon J, Mdoe P, Mduma E, Manyahi J, Pettersen VK, Paschal J, Syre H, Bukhay R, Klingenberg C, Langeland N. Navigating the trials of a trial: lessons from ProRIDE on recruitment, retention, and follow-up in rural Africa. Trials. 2026 Jan 15;27(1):125. doi: 10.1186/s13063-026-09447-3.
PubMed 41535953Klingenberg C, Justine M, Moyo SJ, Lohr IH, Gideon J, Mdoe P, Mduma E, Manyahi J, Bargheet A, Pettersen VK, Paschal J, Syre H, Bernhoff E, Bukhay R, Blomberg B, Langeland N. Home administration of a multistrain probiotic once per day for 4 weeks to newborn infants in Tanzania (ProRIDE): a double-blind, placebo-controlled randomised trial. Lancet Glob Health. 2025 Jun;13(6):e1082-e1090. doi: 10.1016/S2214-109X(25)00064-6.
PubMed 40412397Kuwelker K, Langeland N, Lohr IH, Gidion J, Manyahi J, Moyo SJ, Blomberg B, Klingenberg C. Use of probiotics to reduce infections and death and prevent colonization with extended-spectrum beta-lactamase (ESBL)-producing bacteria among newborn infants in Tanzania (ProRIDE Trial): study protocol for a randomized controlled clinical trial. Trials. 2021 Apr 29;22(1):312. doi: 10.1186/s13063-021-05251-3.
PubMed 33926519
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Probiotics to Reduce Infections and Death and Prevent Colonization With Extended-spectrum Beta-lactamase Producing Bacteria, Among Newborn Infants in Haydom and Surrounding Area, Tanzania, a Randomized Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT04172012
- Acronym / sponsor ID
- ProRIDE / 2019/1025
- Conditions
- Neonatal Sepsis
- Keywords
- Tanzania, East Africa, Antimicrobial resistance, Probiotics, Extended Spectrum Beta-Lactamase Producing Bacteria
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,000 participants (actual)
- Lead sponsor
- Haydom Lutheran HospitalUniversity, hospital or other
- Collaborators
- University of Bergen, Helse Stavanger HF, UiT The Arctic University of Norway, Muhimbili University of Health and Allied Sciences
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- 10 Jul 2023 (actual)
- Study completion
- 19 Sep 2023 (actual)
- First posted
- 21 Nov 2019 (actual)
- 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.
This study examines the effect of oral probiotic treatment to newborns on preventing hospitalizations, death and colonization with Extended-spectrum beta-lactamase-producing Gram negative bacteria. Half of the babies will receive 4 weeks treatment with an oral mixture of the probiotic Labinic (R) while the other half will receive a placebo mixture.
Detailed description
Studies show that probiotics given to prematurely born babies prevents sepsis and is widely used in the western world for this purpose. Probiotics consists of one or more normal gut-bacteria. A large study in India showed that giving probiotics to full-born babies reduced hospitalizations and morbidity. This study investigates giving a probiotic mixture with different combination of bacteria, Lactobacillus acidophilus, Bifidobacterium infantis and Bifidobacterium breve, for a longer duration (4 weeks instead of 7 days).
Infections with antibiotic-resistant bacteria is a major threat to health-care world-wide, and sepsis/severe infection caused by such bacteria is a major cause of neonatal death. The study hypothesis is that giving probiotics to newborns prevents them from getting colonized with antibiotic-resistant bacteria, such as Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). By preventing colonization with ESBL-PE, severe infections such as sepsis may be prevented, and thereby survival may be improved.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Placebo-controlled double-blinded randomized clinical trial
| Arm | Type | Receives |
|---|---|---|
| Probiotic | Active comparator | Biological: Labinic (R) probiotic mixtureStudy subjects receive probiotic mixture for 4 weeks |
| Placebo | Placebo comparator | Other: PlaceboStudy subjects receive placebo mixture for 4 weeks |
Who may qualify
- Ages
- Up to 3 days
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Healthy newborn infants with a birth weight equal or above 2.0 kgs, will be included in the study between 0-3 days of life.
- Newborn infants have to come from families who are long-term or permanent residents in the defined catchment area for this trial (30 km radius from HLH) in Tanzania.
- Parents are able and willing to complete study visit (including required study procedures) schedules over the six months proposed follow-up, which also includes hospitalizations required for compliance of this study protocol.
- Parents agrees for the child not to participate in another study during the study period
- Children less than one year admitted to hospital with suspected infection, not included in the RCT, will be included in a sub-study. A separate inclusion form is prepared for these children.
Key exclusion criteria (4 listed)
- Birth weight below 2 kg
- Other health problems/illness, obvious congenital malformations.
- Multiple pregnancy
- Parents not consenting
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 |
|---|---|---|
| Labinic (R) probiotic mixtureLabinic (R) probiotic mixture containing Lactobacillus acidophilus and Bifidobacterium infantis and B. breve | Biological | Probiotic |
| PlaceboPlacebo mixture | Other | Placebo |
Primary outcome
Composite outcome hospitalization and death
Time frame: 6 months from inclusion
Primary outcome is hospitalization and/or death of study subject
12 secondary outcomes
ESBL colonization
Time frame: 6 weeks and 6 months
Hospitalisation
Time frame: 6 weeks and 6 months
Death
Time frame: 6 months
Body weight
Time frame: 6 months
Body length
Time frame: 6 months
Stool microbiota
Time frame: 6 weeks and 6 months
Stool metabolome
Time frame: 6 weeks and 6 months
Stool inflammatory markers - Calprotectin
Time frame: 6 weeks and 6 months
Stool inflammatory markers - alpha-1 antitrypsin
Time frame: 6 weeks and 6 months
Stool inflammatory markers - myeloperoxidase
Time frame: 6 weeks and 6 months
Number of participants with culture-confirmed bacteremia
Time frame: 6 months
Genetic characteristics of ESBL-producing Enterobacteriaceae
Time frame: 6 weeks and 6 months
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 25 Apr 2025.
- Background: PubMed 28813414Panigrahi P, Parida S, Nanda NC, Satpathy R, Pradhan L, Chandel DS, Baccaglini L, Mohapatra A, Mohapatra SS, Misra PR, Chaudhry R, Chen HH, Johnson JA, Morris JG, Paneth N, Gewolb IH. A randomized synbiotic trial to prevent sepsis among infants in rural India. Nature. 2017 Aug 24;548(7668):407-412. doi: 10.1038/nature23480. Epub 2017 Aug 16.
- Background: PubMed 30505830Esaiassen E, Hjerde E, Cavanagh JP, Pedersen T, Andresen JH, Rettedal SI, Stoen R, Nakstad B, Willassen NP, Klingenberg C. Effects of Probiotic Supplementation on the Gut Microbiota and Antibiotic Resistome Development in Preterm Infants. Front Pediatr. 2018 Nov 16;6:347. doi: 10.3389/fped.2018.00347. eCollection 2018.
- Background: PubMed 27936054Tellevik MG, Blomberg B, Kommedal O, Maselle SY, Langeland N, Moyo SJ. High Prevalence of Faecal Carriage of ESBL-Producing Enterobacteriaceae among Children in Dar es Salaam, Tanzania. PLoS One. 2016 Dec 9;11(12):e0168024. doi: 10.1371/journal.pone.0168024. eCollection 2016.
- Derived from this study: PubMed 41535953Moyo SJ, Justine M, Blomberg B, Lohr IH, Gideon J, Mdoe P, Mduma E, Manyahi J, Pettersen VK, Paschal J, Syre H, Bukhay R, Klingenberg C, Langeland N. Navigating the trials of a trial: lessons from ProRIDE on recruitment, retention, and follow-up in rural Africa. Trials. 2026 Jan 15;27(1):125. doi: 10.1186/s13063-026-09447-3.
- Derived from this study: PubMed 40412397Klingenberg C, Justine M, Moyo SJ, Lohr IH, Gideon J, Mdoe P, Mduma E, Manyahi J, Bargheet A, Pettersen VK, Paschal J, Syre H, Bernhoff E, Bukhay R, Blomberg B, Langeland N. Home administration of a multistrain probiotic once per day for 4 weeks to newborn infants in Tanzania (ProRIDE): a double-blind, placebo-controlled randomised trial. Lancet Glob Health. 2025 Jun;13(6):e1082-e1090. doi: 10.1016/S2214-109X(25)00064-6.
- Derived from this study: PubMed 33926519Kuwelker K, Langeland N, Lohr IH, Gidion J, Manyahi J, Moyo SJ, Blomberg B, Klingenberg C. Use of probiotics to reduce infections and death and prevent colonization with extended-spectrum beta-lactamase (ESBL)-producing bacteria among newborn infants in Tanzania (ProRIDE Trial): study protocol for a randomized controlled clinical trial. Trials. 2021 Apr 29;22(1):312. doi: 10.1186/s13063-021-05251-3.
- Individual participant dataSharing planned: No
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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.
Nina Langeland, MD, PhD principal investigator
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 Labinic (R) probiotic mixture in people with Neonatal Sepsis, run by Haydom Lutheran Hospital at 1 site in Tanzania.
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 5 inclusion and 4 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 25 Apr 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 Tanzania. 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. Some participants in this study may receive a placebo. 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?
Composite outcome hospitalization and death (time frame: 6 months from inclusion). 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 NCT04172012, which also lists 6 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 25 Apr 2025.