SepsisCLEANNCT06824350
Clean Trial - Chlorination to Reduce Enteric and Antibiotic Resistant Infections in Neonates
A study testing chlorination for water disinfection and surface disinfection in people with Sepsis and Neonatal Mortality, run by University of California, Berkeley at 2 sites in 2 countries.
Trial summary
The CLEAN (ChLorine to reduce Enteric and Antibiotic resistant infections in Neonates) cluster randomized controlled trial in western Kenya will evaluate the impact of a multi-component chlorination intervention in health care facilities on maternal and neonatal health. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Sepsis, Neonatal Mortality, Antibiotic Resistant Infection
- What is being tested?
- chlorination for water disinfection and surface disinfection
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45,450 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 21 Jan 2025to Jul 2027
- Phase
- Interventional
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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Facility Inclusion Criteria:
- Public health care facility
- 25 live births or more per month
- Infrastructure compatible with inline chlorination device
Participant Inclusion Criteria:
- Pregnant adults/mature minors arriving at enrolled facilities to give birth and their neonates
Facility Exclusion Criteria:
- Existing facility-level chlorination
Participant Exclusion Criteria:
- Miscarriage (<28 weeks gestation)
- Stillbirth (for neonatal analysis only)
- Unable to give informed consent/do not consent
- Reside >2 hours away from facility for enrollment into swab sampling cohort
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
United States1 site
- Active, not recruiting
University of California, Berkeley
Berkeley, California, 94720
Kenya1 site, 1 recruiting
- Recruiting
Kenya Medical Research Institute
Nairobi
Phelgona Otieno, PhD, +254-721973971, phelgona@gmail.com
Phelgona Otieno, PhD
About this study
Official title: Multi-component Chlorination Intervention to Reduce Neonatal Infections in Rural Health Facilities
The CLEAN (ChLorine to reduce Enteric and Antibiotic resistant infections in Neonates) cluster randomized controlled trial in western Kenya will evaluate the impact of a multi-component chlorination intervention in health care facilities on maternal and neonatal health. Intervention facilities will receive a passive chlorination technology for water supply treatment and a reliable supply of sodium hypochlorite disinfectant. Both intervention and treatment facilities will receive infection prevention and control messaging. The goal of the study is to evaluate the impact of the intervention on bacterial contamination of water supply, on staff hands, and on high-touch surfaces in maternity wards, and the following outcomes among facility-born neonates and their mothers: (1) gut carriage of bacterial pathogens associated with sepsis one week post-birth, (2) gut carriage of antibiotic resistant bacteria one week post-birth, and (3) symptoms of possible serious bacterial infection one week following birth.
Read the detailed description
The proportion of births occurring at healthcare facilities is rising globally, yet healthcare facilities in low-income settings have been found to be highly contaminated with bacterial pathogens, including antibiotic resistant pathogens. There is a need for effective strategies to reduce contamination in healthcare facilities in order to reduce infection risks among facility-born neonates. In this trial, medium-sized public health facilities will be randomized to control or to receive an intervention consisting of passive chlorination for water supply treatment and a reliable supply of chlorine disinfectant. Reliable supply is randomized as either (a) an electrochlorinator for on-site production or (b) bulk chlorine delivery.
This cluster randomized controlled trial will enroll 36 health facilities to generate rigorous evidence on the maternal and neonatal health benefits of chlorinated water supply paired with reliable supplies of chlorine disinfectant. This study has the following aims: 1) determine the impact of the intervention on pathogenic and antibiotic resistant bacterial contamination in water supplies, on high-touch surfaces, and on healthcare worker hands, 2) quantify intervention effects on gut colonization of mothers and neonates by a panel of pathogenic and antibiotic resistant bacteria species linked to serious infection, using molecular and culture-based methods, and 3) follow up with mother-neonate dyads to measure intervention effects on symptoms of possible serious bacterial infection in the week following birth. Data collection will be for a duration of 24 months.
Infection prevention through effective water, sanitation, and hygiene (WASH) has been cited by national action plans as a key tool in the fight against antimicrobial resistance and, while global data show dire WASH conditions in low- and middle-income (LMIC) health facilities, there exists very little guidance for implementing effective interventions. The overarching goal is to generate actionable evidence to inform investments in chlorination at health facilities to improve maternal and neonatal health and reduce the threat of antibiotic resistant infections.
- Conditions
- Sepsis, Neonatal Mortality, Antibiotic Resistant Infection, Enteric Infections, Serious Bacterial Infection
- Being tested
- chlorination for water disinfection and surface disinfection, infection prevention and control messaging
- Keywords
- infection prevention and control, antibiotic resistance, bacterial enteric infection, neonatal mortality, sepsis, water disinfection, chlorine, sodium hypochlorite, hospital acquired infections
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
chlorination for water disinfection and surface disinfectionDevice
- Installation of inline chlorine doser(s) for automated water disinfection.
- Provision of chlorine solution for water and surface disinfection (half of treatment facilities randomized to receive electrochlorinator, half receive bulk chlorine solution deliveries).
- Provision of mop(s), bucket(s), and spray bottles for surface cleaning.
infection prevention and control messagingBehavioural
Infection prevention and control guidance and messaging
| Study group | Role | What they receive |
|---|---|---|
| Control | Active comparator | Control group. At the conclusion of the trial, facilities will receive a chlorine doser. Receives: Behavioral: infection prevention and control messaging |
| Multi-component chlorine intervention | Experimental | Health care facilities will receive one or more inline chlorine dosers that will automatically chlorinate all water accessed by the maternity wards. Intervention facilities will also be randomized to either receive an electrochlorinator for on-site production of liquid chlorine solution or to receive bulk chlorine deliveries. Chlorine will be use to refill the chlorine dosers and for surface disinfection. Facilities will also receive hardware to facilitate surface disinfection. Receives: Device: chlorination for water disinfection and surface disinfection; Behavioral: infection prevention and control messaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Possible serious bacterial infection in neonate
Cumulative incidence of one or more of the following severe infection symptoms of neonates based on WHO criteria for possible serious bacterial infection:
- Not able to feed at all or not feeding well
- Convulsions
- Severe chest indrawing
- Fever - High body temperature (38°C* or above)
- Low body temperature (less than 35.5°C*)
- Movement only when stimulated or no movement at all
- Fast breathing (60 breaths per minute or more)
Measured: From birth to 7 days post birth
Possible maternal sepsis
Any of the following listed with fever or hypothermia:
- fast heartbeat
- low blood pressure
- respiratory distress
- jaundice
- decreased urination/dysuria
- altered mental status
Measured: From birth to 7 days post birth
Neonatal infection with at least one bacterial pathogen
Detection of any pre-specified bacterial pathogen detected by qPCR in infant rectal swabs (among swab subset of participants)
Includes:
ETEC, STEC, EPEC, EAEC, EIEC, EHEC O157:H7, Escherichia coli, Shigella spp, Shigella flexneri, Salmonella spp., Salmonella typhi, Campylobacter jejuni/coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus agalactiae (Group B strep), Pseudomonas aeruginosa, Acinetobacter baumannii, Clostridium difficile, Streptococcus pyogenes (Group A strep), Citrobacter freundii/braaki, Enterobacter cloacae
Measured: 7 days after birth
Neonatal rectal colonization with at least one bacterial pathogen by culture-based method measured 7 days after birth
Detection of any pre-specified bacterial pathogen detected by culture in neonate rectal swabs (among swab subset of participants)
Includes: Salmonella spp., Shigella, Staphylococcus aureus,Streptococcus agalactiae (Group B strep)
Measured: Approx 7 days after birth
Rectal colonization with one or more antibiotic resistant bacteria (neonates)
Detection of ESBL enterobacteriaceae by culture in rectal swabs
Includes: Klebsiella spp./Enterobacter/Citrobacter spp. (KEC), Acinetobacter spp., Pseudomonas spp., E. coli
Measured: Approx 7 days after birth
Secondary outcomes (25)
Maternal rectal colonization with at least one bacterial pathogen by culture-based method
Detection of any pre-specified bacterial pathogen detected by culture in maternal rectal swabs (among swab subset of participants)
Includes: Salmonella spp., Shigella spp., Staphylococcus aureus
Measured: 7 days post birth
Any symptom or sign of infection in neonate
One or more of the following symptoms:
Difficulty feeding, Hyperthermia/fever, Hypothermia, Tachypnea, Severe chest indrawing, Convulsions, Movement only when stimulated/no movement, Bulging fontanel, Labored breathing, Skin infection, Umbilical redness, Oozing ears, Diarrhea, Three or more loose or watery stools in a 24 hour period, Vomiting, Cyanosis, Cough, Runny nose or congestion, Tachycardia (>160 bpm at rest)
Measured: From birth until 7 days post birth
Any symptom or sign of infection in mother
One or more of the following symptoms:
Hypothermia, Fever, Foul smelling vaginal discharge, Fits/convulsions, Tachycardia (>100 bpm at rest), Low blood pressure, Diarrhea (self-defined), Difficulty breathing, Jaundice, Decreased urination or difficult or painful urination, Confusion or altered mental state, Mastitis, Chills, Body aches, Low appetite, Lower abdominal pain, Three or more loose or watery stools in a 24 hour period, Vomiting, Cough, Runny nose or congestion, Chest pain, Bloody stool, Skin infection
Measured: From birth to 7 days post birth
Clinical diagnosis of sepsis in neonate
Abstracted diagnosis from medical charts OR self-reported diagnosis confirmed by clinician
Measured: From birth to 7 days post birth
Clinical diagnosis of sepsis in mother
Abstracted diagnosis from medical charts OR self-reported diagnosis confirmed by clinician
Measured: From birth to 7 days post birth
Neonatal hospitalization in first 7 days of life
Self-reported or confirmed by medical records
Measured: Birth to 7 days
Maternal hospitalization in first 7 days post-partum
Self-reported or confirmed by medical records
Measured: Birth to 7 days
Neonatal mortality
Report of neonatal death up to 28 days
Measured: From birth to 28 days after birth
Maternal mortality
Report of maternal death
Measured: From birth to 28 days after birth
Number of clinically relevant antibiotic resistance genes (ARGs) detected in neonatal rectal swabs
Measured by qPCR. Includes: resistance to quinolone, macrolide, sulfonamide, tetracycline, vancomycin,, aminoglycoside, beta-lactams (cephalosporin, penicillin, ampicillin), carbapenem, colistin
Measured: 7 days post birth
Number of clinically relevant antibiotic resistance genes (ARGs) detected in maternal rectal swabs
Measured by qPCR. Includes: resistance to quinolone, macrolide, sulfonamide, tetracycline, vancomycin,, aminoglycoside, beta-lactams (cephalosporin, penicillin, ampicillin), carbapenem, colistin
Measured: Approx 7 days post birth
Number of bacterial pathogens in rectal swabs (mothers)
Number of unique bacterial pathogens (see pre-specified list above) by culture
Measured: 7 days postpartum
Number of bacterial pathogens in rectal swabs (neonates)
Number of unique bacterial pathogens (see pre-specified list above) detected by qPCR
Measured: 7 days post birth
Number of bacterial pathogens in rectal swabs (neonates)
Number of unique bacterial pathogens (see pre-specified list above) by culture
Measured: 7 days post birth
Rectal colonization with one or more antibiotic resistant bacteria (mothers)
Detection of ESBL enterobacteriaceae by culture in rectal swabs
Includes: Klebsiella spp./Enterobacter/Citrobacter spp. (KEC), Acinetobacter spp., Pseudomonas spp., E. coli
Measured: 7 days postpartum
Presence and concentration of bacterial pathogens on high touch surfaces
Measured by culture-based assays
Includes: Acinetobacter spp., Pseudomonas spp., Staphylococcus aureus
Measured: baseline and 4,8,12, 16, 20, and 24 months post-intervention
Detection of bacterial pathogens in environmental samples
Detection of any pre-specified bacterial pathogen detected by qPCR in water, hand rinse, and high touch surface samples (among subset of samples)
Includes: targets listed above for rectal swabs
Measured: at 16 and 20 months post-intervention
Detection of clinically relevant antibiotic resistance genes (ARGs) in environmental samples
Detection of any pre-specified ARG detected by qPCR in water, hand rinse, and high touch surface samples (among subset of samples)
Includes: targets listed above for rectal swabs
Measured: at 16 and 20 months post-intervention
Presence and concentration of antibiotic resistant bacterial pathogens on high touch surfaces
Detection of ESBL enterobacteriaceae by culture in surface swabs
Includes: Klebsiella spp./Enterobacter/Citrobacter spp. (KEC), Acinetobacter spp., Pseudomonas spp., E. coli
Measured: baseline and 4,8,12, 16, 20, and 24 months post-intervention
Proportion of water samples meeting WHO "safe" criteria
Measured as <1 CFU E. coli per 100ml water tested by culture
Measured: baseline and 4,8,12, 16, 20, and 24 months post intervention
Concentration of E. coli / 100 ml water
Measured by culture-based membrane filtration assay
Measured: Baseline, and 4, 8, 12, 16, and 24 months post-intervention
Presence and concentration of E. coli and total coliform on healthcare staff hands
Measured by membrane filtration culture assay
Measured: baseline and 4,8,12, 16, 20, and 24 months post-intervention
Presence and concentration of antibiotic resistant bacterial pathogens on healthcare staff hands
Detection of ESBL enterobacteriaceae by culture in hand rinses and swabs
Includes: Klebsiella spp./Enterobacter/Citrobacter spp. (KEC), Acinetobacter spp., Pseudomonas spp., E. coli
Measured: baseline and 4,8,12, 16, 20, and 24 months post-intervention
Proportion of water supply samples with detectable free chlorine residual in water
Measured as >=0.1 ppm by DPD method
Measured: baseline and 4,8,12, 16, 20, and 24 months post-intervention
Proportion of water samples with detectable total chlorine
Measured as >=0.1 ppm total chlorine by DPD method
Measured: At least monthly from baseline up to 24 months post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2025
- Study start21 Jan 2025
- Primary completionJul 2027 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 45,450 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, Berkeley
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Kenya Medical Research Institute, Walter Reed Army Institute of Research (WRAIR)
- Responsible party
- Sponsor
- Investigators
- Amy J Pickering, PhD, Principal investigator, University of California, BerkeleyPhelgona Otieno, PhD, Principal investigator, Kenya Medical Research InstituteLillian Musila, PhD, Principal investigator, Walter Reed Army Institute of Research-Africa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06824350
- Sponsor's protocol ID
- 2024-01-17100
- Other IDs
- R01AI184756
- Acronym
- CLEAN
- Status last verified
- Sep 2026
- First submitted
- 7 Feb 2025
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Any data shared will be de-identified. Participants will not be contacted or re-consented for future sharing or accessing data through repositories. Privacy and confidentiality protections will be consistent with applicable local laws in Kenya. Data will be de-identified prior to sharing. All data sharing plans will be reviewed and approved by the respective institutional review boards at all participating institutions and will be reviewed during the informed consent process with caregivers.
Publications
Lindmark M, Cherukumilli K, Crider YS, Marcenac P, Lozier M, Voth-Gaeddert L, Lantagne DS, Mihelcic JR, Zhang QM, Just C, Pickering AJ. Passive In-Line Chlorination for Drinking Water Disinfection: A Critical Review. Environ Sci Technol. 2022 Jul 5;56(13):9164-9181. doi: 10.1021/acs.est.1c08580. Epub 2022 Jun 14.
PubMed 35700262Pickering AJ, Crider Y, Sultana S, Swarthout J, Goddard FG, Anjerul Islam S, Sen S, Ayyagari R, Luby SP. Effect of in-line drinking water chlorination at the point of collection on child diarrhoea in urban Bangladesh: a double-blind, cluster-randomised controlled trial. Lancet Glob Health. 2019 Sep;7(9):e1247-e1256. doi: 10.1016/S2214-109X(19)30315-8.
PubMed 31402005Crider YS, Chiyenge M, Odoyo E, Kisiangani J, Lowe J, Wangia J, Bwire B, Kioko M, Alexander KT, Nekesa C, Musila L, Otieno P, Pickering AJ. Multi-component chlorination intervention to reduce neonatal infections in healthcare facilities in western Kenya (CLEAN Trial): study protocol for a cluster randomized controlled trial. medRxiv [Preprint]. 2026 Sep 21:2026.09.18.26363445. doi: 10.64898/2026.09.18.26363445.
PubMed 42818399