Development and Evaluation of a ChlorHexidine Gluconate b... | NCT06590675

Status Module

Name	Class
Children's Hospital of Philadelphia	OTHER
University of Botswana	OTHER
Centers for Disease Control and Prevention	FED
University of Utah

Description Module

Detailed Description

Neonatal sepsis is the third most common cause of neonatal deaths and multidrug-resistant Gram-negative bacteria are now the leading cause of sepsis among hospitalized neonates in south Asia and sub-Saharan Africa, including Botswana. Multidrug-Resistant Organism (MDRO) colonization is thought to precede infection, meaning that pathogens usually are transferred to the skin or intestinal mucosa where they live prior to translocating to the bloodstream or other sterile body compartments, triggering an inflammatory response recognized as clinical sepsis. Colonization is established through direct or indirect contact between a patient and a reservoir that harbors the pathogen.

Multidisciplinary infection prevention and control (IPC) practices can reduce the risk of neonatal MDRO colonization, but once colonized, newborns run the risk of acquiring a serious infection with a difficult-to-treat organism. The use of ancillary IPC measures, including chlorhexidine gluconate (CHG) bathing, has been studied as a de-colonization measure among hospitalized patients. CHG bathing is widely used in Intensive Care Units (ICUs) across high-income countries to reduce bacterial colonization with pathogens, and is being used more frequently in Neonatal Units (NNUs) in low and middle-income countries (LMICs) as a sepsis prevention measure.

The investigators of the CHARM study have developed a protocol to accomplish the following goals:

develop a low-cost, standardized protocol for CHG bathing in the ICU and NNU
assess safety of local CHG preparation among hospitalized neonates
determine the efficacy of CHG bathing using the developed protocol to reduce bacterial colonization and healthcare-associated infection (HAI) burden in hospitalized patients
to assess the feasibility and acceptability of CHG bathing among staff and caregivers

The investigators will utilize a mixed methods study involving both a prospective interventional cohort study following approximately 240 neonates, and qualitative interviews of 10 caregivers and 20 healthcare workers in the NNU and ICU.

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
≥34 Week Neonates & ≥1.4 kg	Experimental	Phase 1 of a step-wise enrollment strategy in which chlorhexidine gluconate (CHG) bathing will be administered as follows: 1% CHG administered twice (2) a week (N=10) 1% CHG administered five times (5) a week (N=10) 2% CHG administered twice (2) a week (N=10) 2% CHG administered five times (5) a week (N=10)	Drug: Chlorhexidine Gluconate (CHG)
≥32 Week Neonates &/or 1.2 kg - 1.4 kg	Experimental	Phase 2 of a step-wise enrollment strategy in which chlorhexidine gluconate (CHG) bathing will be administered as follows: 1% CHG administered twice (2) a week (N=20) 1% CHG administered five times (5) a week (N=20) 2% CHG administered twice (2) a week (N=20) 2% CHG administered five times (5) a week (N=20)	Drug: Chlorhexidine Gluconate (CHG)
≥28 Week Neonates &/or 1.0 kg - 1.2 kg	Experimental	Phase 3 of a step-wise enrollment strategy in which chlorhexidine gluconate (CHG) bathing will be administered as follows: 1% CHG administered twice (2) a week (N=30) 1% CHG administered five times (5) a week (N=30) 2% CHG administered twice (2) a week (N=30) 2% CHG administered five times (5) a week (N=20)	Drug: Chlorhexidine Gluconate (CHG)
Feasibility Assessment	No Intervention	Semi-structured, qualitative Interviews will be performed with caregivers (N=10) of neonates enrolled in the interventional arms and with healthcare workers (N=20) who care for these neonates in the neonatal unit (NNU) and intensive care unit (ICU).

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Chlorhexidine Gluconate (CHG)	Drug	A locally-prepared CHG formulation as a 1% or 2% solution	≥28 Week Neonates &/or 1.0 kg - 1.2 kg ≥32 Week Neonates &/or 1.2 kg - 1.4 kg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Safety of locally prepared 1% and 2% chlorhexidine gluconate (CHG) cleansing: Skin integrity	Skin condition score: Assessing skin reactions in neonates by a trained study nurse using the Darmstadt scale. The skin of the neonate will be assessed using a scale of 1 to 9, with 1 being the best condition and 9 being the worst condition, based on the following variables: skin breakdown, skin dryness, and erythema. Stopping rule: Skin fissuring (skin score of >3)	At baseline and 30 minutes post application of CHG solution
Safety of locally prepared 1% and 2% CHG cleansing: Systemic responses	Temperature assessments will be performed at baseline and 30 min after application. If hypothermia is detected (defined as temperature below 36.5 C when measured from the same site at 30 minutes), the baby will be bundled and temperature retaken after 30 additional minutes. Babies will also be observed for 30 min for signs of anaphylaxis. Respiratory distress, cyanosis, urticaria, edema, vomiting/diarrhea, or lethargy will elicit a full set of vital signs to assess for hypotension and tachycardia. Stopping rule: Anaphylaxis, or any other rapid decompensation not explained by a patient's concurrent conditions	At baseline and 30 minutes post application of CHG solution

Secondary Outcomes

Measure	Description	Time Frame
Reduction in pathogen colonization of participants receiving CHG cleansing: -1% vs 2% CHG -2x vs 5x weekly frequency	Trained research personnel will use flocked swabs to collect perirectal and umbilical swabs. For perirectal samples, the swab tip will be gently introduced around the anus. For skin samples, a single swab will be rubbed back-and-forth around the umbilicus. All swabs collected from neonates will be placed into transport media. The samples will be labeled with the infant's study number, source of sample and timing of sample. At the National Health Laboratory microbiology section, swab specimens will be directly inoculated on chromogenic culture media which is selective and differential for select multidrug-resistant organisms (MDROs). MDRO isolates will then undergo confirmatory identification and sensitivity testing using the VITEK® 2 platform. Results will be available within 72 hrs of delivery to the laboratory.

Eligibility Module

Name	Affiliation	Role
Ebbing Lautenbach, MD,MPH,MSCE	University of Pennsylvania	Principal Investigator
Susan Coffin, MD,MPH	Children's Hospital of Philadelphia	Principal Investigator

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
33227511	Background	Gezmu AM, Bulabula ANH, Dramowski A, Bekker A, Aucamp M, Souda S, Nakstad B. Laboratory-confirmed bloodstream infections in two large neonatal units in sub-Saharan Africa. Int J Infect Dis. 2021 Feb;103:201-207. doi: 10.1016/j.ijid.2020.11.169. Epub 2020 Nov 20.
27031259	Background	Kabwe M, Tembo J, Chilukutu L, Chilufya M, Ngulube F, Lukwesa C, Kapasa M, Enne V, Wexner H, Mwananyanda L, Hamer DH, Sinyangwe S, Ahmed Y, Klein N, Maeurer M, Zumla A, Bates M. Etiology, Antibiotic Resistance and Risk Factors for Neonatal Sepsis in a Large Referral Center in Zambia. Pediatr Infect Dis J. 2016 Jul;35(7):e191-8. doi: 10.1097/INF.0000000000001154.