Clinical trial NCT06824350: Clean Trial - Chlorination to Reduce Enteric and Antibiotic Resistant Infections in Neonates
Official title: Multi-component Chlorination Intervention to Reduce Neonatal Infections in Rural Health Facilities
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sepsis
Neonatal Mortality
Antibiotic Resistant Infection
Enteric Infections
Serious Bacterial Infection
Keywords: infection prevention and control
antibiotic resistance
bacterial enteric infection
neonatal mortality
sepsis
water disinfection
chlorine
sodium hypochlorite
hospital acquired infections
Lead sponsor: University of California, Berkeley
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Kenya Medical Research Institute
name: Walter Reed Army Institute of Research (WRAIR)
First posted: 2025-02-13
Enrollment: 45450
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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. 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Possible serious bacterial infection in neonate
timeFrame: From birth to 7 days post birth
measure: Possible maternal sepsis
timeFrame: From birth to 7 days post birth
measure: Neonatal infection with at least one bacterial pathogen
timeFrame: 7 days after birth
Secondary outcomes:
measure: Any symptom or sign of infection in neonate
timeFrame: From birth until 7 days post birth
measure: Any symptom or sign of infection in mother
timeFrame: From birth to 7 days post birth
measure: Clinical diagnosis of sepsis in neonate
timeFrame: From birth to 7 days post birth
measure: Clinical diagnosis of sepsis in mother
timeFrame: From birth to 7 days post birth
measure: Neonatal mortality
timeFrame: From birth to 28 days after birth
measure: Maternal mortality
timeFrame: From birth to 28 days after birth
measure: Neonatal rectal colonization with at least one bacterial pathogen by culture
timeFrame: 7 days after birth
measure: Maternal rectal colonization with at least one bacterial pathogen by culture-based method
timeFrame: 7 days postpartum
measure: Number of clinically relevant antibiotic resistance genes (ARGs) detected in neonatal rectal swabs
timeFrame: 7 days post birth
measure: Rectal colonization with one or more antibiotic resistant bacteria (neonates)
timeFrame: 7 days post birth
measure: Rectal colonization with one or more antibiotic resistant bacteria (mothers)
timeFrame: 7 days postpartum
measure: Number of bacterial pathogens in rectal swabs (neonates)
timeFrame: 7 days post birth
measure: Number of bacterial pathogens in rectal swabs (mothers)
timeFrame: 7 days postpartum
Other outcomes:
measure: Rectal colonization with individual bacterial pathogens (neonates)
timeFrame: 7 days post birth
measure: Rectal colonization with individual bacterial pathogens (mothers)
timeFrame: 7 days postpartum
measure: Presence of individual ARGs in neonatal rectal swabs
timeFrame: 7 days post birth
measure: Presence and concentration of bacterial pathogens on high touch surfaces
timeFrame: Measured quarterly over 24 months post intervention delivery (every 3 months)
measure: Presence and concentration of antibiotic resistant bacterial pathogens on high touch surfaces
timeFrame: Measured quarterly over 24 months post intervention delivery (every 3 months)
measure: Proportion of water samples meeting WHO "safe" criteria
timeFrame: Measured quarterly over 24 months post intervention delivery (every 3 months)
measure: Concentration of E. coli / 100 ml water
timeFrame: Measured quarterly over 24 months post intervention delivery (every 3 months)
measure: Presence and concentration of E. coli and total coliform on healthcare staff hands
timeFrame: Measured quarterly over 24 months post intervention delivery (every 3 months)
measure: Presence and concentration of antibiotic resistant bacterial pathogens on healthcare staff hands
timeFrame: Measured quarterly over 24 months post intervention delivery (every 3 months)
measure: Proportion of water supply samples with detectable free chlorine residual in water
timeFrame: Measured quarterly over 24 months post intervention delivery (every 3 months)
Locations:
city: Berkeley
country: United States
facility: University of California, Berkeley
state: California
city: Nairobi
country: Kenya
facility: Kenya Medical Research Institute
Study officials:
affiliation: University of California, Berkeley
name: Amy J Pickering, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kenya Medical Research Institute
name: Phelgona Otieno, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Walter Reed Army Institute of Research-Africa
name: Lillian Musila, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Pickering 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.