Clean Trial - Chlorination to Reduce Enteric and Antibiotic Resistant Infections in Neonates

Not Applicable

Recruiting

• Conditions: Sepsis; Neonatal Mortality; Antibiotic Resistant Infection; Enteric Infections; Serious Bacterial Infection

• Registration Number: NCT06824350
• Lead Sponsor: University of California, Berkeley

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.

Study Timeline

• Study Start: 2025-01-21
• Study First Submitted: 2025-02-07
• Study First Submitted QC: 2025-02-07
• Study First Posted: 2025-02-13
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-20
• Last Update Posted: 2025-05-25
• Primary Completion: 2027-07
• Study Completion: 2027-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 45450

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Possible serious bacterial infection in neonate	From birth to 7 days post birth	Incidence of one or more of the following severe infection symptoms of neonates based on WHO criteria for possible serious bacterial infection: 1. Not able to feed at all or not feeding well; 2. Convulsions; 3. Severe chest indrawing; 4. Fever - High body temperature (38°C\* or above); 5. Low body temperature (less than 35.5°C\*); 6. Movement only when stimulated or no movement at all; 7. Fast breathing (60 breaths per minute or more)
Possible maternal sepsis	From birth to 7 days post birth	Any of the following listed with fever or hypothermia: 1. fast heartbeat; 2. low blood pressure; 3. respiratory distress; 4. jaundice; 5. decreased urination/dysuria; 6. altered mental status
Neonatal infection with at least one bacterial pathogen	7 days after birth	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, Shigella spp, Shigella flexneri, Salmonella spp., Salmonella enteritidis, Salmonella typhi, Campylobacter jejuni/coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus agalactiae (Group B strep), Serratia marcescens, Pseudomonas aeruginosa, Acinetobacter baumannii, Clostridium difficile, Vibrio cholerae

Secondary Outcome Measures

Name	Time	Method
Any symptom or sign of infection in neonate	From birth until 7 days post birth	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)
Any symptom or sign of infection in mother	From birth to 7 days post birth	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
Clinical diagnosis of sepsis in neonate	From birth to 7 days post birth	Abstracted diagnosis from medical charts OR self-reported diagnosis confirmed by clinician
Clinical diagnosis of sepsis in mother	From birth to 7 days post birth	Abstracted diagnosis from medical charts OR self-reported diagnosis confirmed by clinician
Neonatal mortality	From birth to 28 days after birth	Report of neonatal death up to 28 days
Neonatal rectal colonization with at least one bacterial pathogen by culture	7 days after birth	Detection of any pre-specified bacterial pathogen detected by culture in neonate rectal swabs (among swab subset of participants); Includes: Acinetobacter spp., Pseudomonas spp., Salmonella spp., Shigella, Staphylococcus aureus, Group B streptococcus
Number of bacterial pathogens in rectal swabs (mothers)	7 days postpartum	Number of unique bacterial pathogens (see pre-specified list above) by culture
Maternal mortality	From birth to 28 days after birth	Report of maternal death
Maternal rectal colonization with at least one bacterial pathogen by culture-based method	7 days postpartum	Detection of any pre-specified bacterial pathogen detected by culture in maternal rectal swabs (among swab subset of participants); Acinetobacter spp., Pseudomonas spp., Salmonella spp., Shigella spp., Staphylococcus aureus, Group B streptococcus
Number of clinically relevant antibiotic resistance genes (ARGs) detected in neonatal rectal swabs	7 days post birth	Measured by qPCR. Includes: resistance to quinolone, macrolide, sulfonamide, tetracycline, vancomycin, aminoglycoside, beta-lactams (cephalosporin, penicillin, ampicillin) , carbapenem, colistin
Rectal colonization with one or more antibiotic resistant bacteria (neonates)	7 days post birth	Detection of ESBL enterobacteriaceae by culture in rectal swabs; Includes: Klebsiella spp./Enterobacter/Citrobacter spp. (KEC), Acinetobacter spp., Pseudomonas spp., E. coli
Rectal colonization with one or more antibiotic resistant bacteria (mothers)	7 days postpartum	Detection of ESBL enterobacteriaceae by culture in rectal swabs; Includes: Klebsiella spp./Enterobacter/Citrobacter spp. (KEC), Acinetobacter spp., Pseudomonas spp., E. coli
Number of bacterial pathogens in rectal swabs (neonates)	7 days post birth	Number of unique bacterial pathogens (see pre-specified list above) detected by qPCR

Trial Locations

Locations (2)

University of California, Berkeley; 🇺🇸 Berkeley, California, United States

Kenya Medical Research Institute; 🇰🇪 Nairobi, Kenya