Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202011513390736 Date of Registration: 11/11/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title The role of a multi-strain probiotic in very low birth weight infants.
Official scientific title The role of a multi-strain probiotic in very low birth weight infants.
Brief summary describing the background and objectives of the trial Background: The third Sustainable Development Goal for child health, aims to end preventable deaths of infants and children under 5 years of age by 2030. This goal cannot be met without reducing infection-related neonatal deaths in low-to-middle income countries. Globally, infections cause an estimated 26% of neonatal deaths, with highest infection-related mortality in Sub-Saharan Africa (250 000 potentially preventable deaths per year). Hypotheses and Specific Aims: Hypothesis: daily supplementation with a multi-strain probiotic will reduce the incidence of rectal colonization with multidrug-resistant Gram-negative bacteria (MDR-GNB), incidence of hospital-acquired bloodstream infections and incidence of necrotizing enterocolitis (NEC), thus reducing morbidity and mortality in preterm neonates compared with a placebo. Specific aims: 1) To determine the incidence of rectal colonization with MDR-GNB, 2) To determine the incidence of bloodstream infections and 3) To determine the incidence of NEC in hospitalized, preterm neonates: we will compare the three incidence estimates between the probiotic and placebo groups. Design: A double-blind, randomized, placebo-controlled clinical trial in very low birth weight (VLBW) preterm (<37 weeks gestation) neonates (750 – 1500g) admitted at Tygerberg Hospital, South Africa. Calculated sample size of 200 neonates or 100 per group. Consecutive sampling to recruit eligible neonates without current clinical or laboratory-confirmed infection at the time of enrolment. Informed consent will be obtained from the mother. We will randomize the 200 participants (1:1) to the probiotic (Labinic TM, intervention group) or to a placebo (control group). Participants will be randomized with a random-sequence number that will be allocated to each participant’s number. All involved will be blinded to the group assignment. Participants will be exited from the study on day 28 after birth (end of the neonatal period) or until infants are discharged
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Digestive System,Neonatal Diseases
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Prevention
Anticipated trial start date 16/11/2020
Actual trial start date
Anticipated date of last follow up 30/11/2021
Actual Last follow-up date
Anticipated target sample size (number of participants) 200
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Labinic probiotic 0,2ml per day Day 28 of life or discharge/death if that occurs earlier. Probiotic strain Standard dose (0.2ml) Lactobacillus acidophilus 0.67 billion Bifidobacterium bifidum 0.67 billion Bifidobacterium infantis 0.67 billion Total Probiotics (CFU) 2 billion CFUs* *Colony forming units (CFU)s 100
Control Group Placebo 0,2ml per day Day 28 of life or discharge/death if that occurs earlier. MCT oil and Aerosil 200 100 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Male and female preterm infants (≥ 27 and < 37 weeks gestational age). Preterm infants with very low birth weight and an extremely low birth weight (<1500g and <1000g). Written maternal consent to the study. Infants with major congenital malformations and/ or developmental disabilities. Infants born with a laboratory-confirmed bloodstream infection (CRP >10 in the first 36h of life). Infants born <750g (as per Periviability protocol in TBCH, these infants receive only specific supportive measures and no NICU care, and thus poses a high lost to follow-up rate due to high mortality and reduces the statistical validity of the study). Preterm infants with major gastro-intestinal abnormalities or surgery of the gastro-intestinal tract. Preterm infants whose mothers were not available within 72 hours post birth / whose mothers did not want their babies to take part in the study (refusal). If the mother is in the intensive care unit (ICU) that cannot give consent (e.g. ventilated, sedated, delirious or unable to provide consent). Premature infant whose mother gave them up for adoption. New born: 0 Day-1 Month 0 Day(s) 28 Day(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 03/11/2020 HREC1 Health Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Stellenbosch University Bellville 7505 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Determine the incidence of rectal colonization with MDR-GNB (extended-spectrum beta-lactamases (ESBL) producing or Carbapenem-resistant Enterobacteriaceae (CRE)) Day 0, 7-10, 14-18
Secondary Outcome To evaluate the efficacy of a multi-strain probiotic in reducing the incidence and severity of hospital-acquired bloodstream infection in premature infants. Day 0 - 28
Secondary Outcome To evaluate the efficacy of a multi-strain probiotic in reducing the incidence and severity of NEC (Bells stage 2 and above) in premature infants. Day 0 - 28
Secondary Outcome To evaluate the efficacy of a multi-strain probiotic in reducing the days until full feeds are reached (150ml/kg). Day 0 - 28
Secondary Outcome Determine the incidence rate of laboratory-confirmed bloodstream infections (LC-BSI). Day 0 - 28
Secondary Outcome To describe the postnatal growth for both probiotic exposed and unexposed premature infants. Day 0 - 28
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Tygerberg Academic Hospital Francie van Zijl Drive Bellville 7505 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
Mrs M Sowden and Prof Dramowski Division of Human Nutrition, Fancie van Zijl Drive, Faculty of Medicine and Health Sciences Bellville Cape Town 7505 South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Safeline Pharmaceuticals 4845 Rugby St, Weltevreden Park, Gauteng Roodepoort 1709 South Africa Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
Prof A Whitelaw Francie van Zijl Bellville 7505 South Africa
Prof A Dramowski Francie van Zijl Bellville 7505 South Africa
Dr E van Niekerk Francie van Zijl Bellville 7505 South Africa
Dr L van Wyk Francie van Zijl Bellville 7505 South Africa
Dr A Bulabula Francie van Zijl Bellville 7505 South Africa
Prof M van Weissenbruch University of Amsterdam Amsterdam Netherlands
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Marwyn Sowden marwyns@sun.ac.za 27219389474 Francie van Zijl Drive
City Postal code Country Position/Affiliation
Bellville 7505 South Africa PhD Student
Role Name Email Phone Street address
Public Enquiries Evette van Niekerk evettev@sun.ac.za 27219389474 Francie van Zijl Drive
City Postal code Country Position/Affiliation
Bellville 7505 South Africa Main study leader
Role Name Email Phone Street address
Scientific Enquiries Lizelle van Wyk lizelle@sun.ac.za 27219389474 Francie van Zijl Drive
City Postal code Country Position/Affiliation
Bellville 7505 South Africa Co study leader and study neonatologist
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Confidentiality and anonymity will be maintained during the study. All participating infants will receive an allocated participant number that will be used for all samples collected and data captured. Data management systems will also ensure the confidentiality of data. All captured data will make use of the allocated participant number, thus excluding personal identifiers, and captured data will be saved using protected passwords. All contact details will also be saved on a separate document. Captured data will be password protected and no data will be shared with external parties. All paper case report forms will be kept in a fire-safe locked cabin. All captured data will be stored in a cloud-based storage. All samples will be de-named, and extra sample material will be destroyed after analysis. Data will not be shared with external parties. Data will only be kept until the thesis and article writing process is completed and approved. Informed Consent Form,Study Protocol We aim to collect the trail data for maximum a year - Nov 2020 to Nov 2021. Data will be captured on RedCap in that time period. Thesis and articles will be written from Dec 2021 - Dec 2022. Only the student and study leaders will have access to the raw data. Only the student, study leaders and statistician will have access to the captured data.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information