Preemptive Ethanol Lock Therapy in Pediatric Bloodstream Infection

Study Overview
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Brief Summary
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The study team will compare hospital length of stay (LOS) and attributable length of stay (ALOS, the LOS attributable to CRI), in a randomized, un-blinded prospective trial utilizing short-dwell ethanol-lock therapy (ELT) (4 hours to 24 hour dwell times per day, repeated for up to 72 hours) placed within 24 - 36 hours of admission(Group 1, Preemptive ELT) versus ELT placed at the time of first positive blood culture report (Group 2, Rescue ELT (Standard of Care ). ELT will be given in both groups, in combination with systemic antibiotics, for the treatment of CRI (suspected or proven) of the blood in children with central catheters. Participants will be enrolled from patients with hematologic/oncologic disorders and bone marrow or hematopoetic stem cell transplants (BMT) admitted for care to Children's Hospital of Michigan (CHM), a tertiary care pediatric hospital in Detroit, Michigan. ALOS will be defined as the number of hospital days between first symptoms of Catheter-related infection (CRI) (or date of admission for those admitted with symptoms) and first negative blood culture. Study Hypothesis: The main hypothesis is that the short-dwell ethanol-lock therapy, defined above, placed within 24 - 36 hours of symptoms/admission (Arm 1) versus ELT placement at the time of first positive blood culture report (Arm 2), with concomitant systemic antibiotics, for the treatment of CRI (suspected or proven) of the blood in children with central catheters in the H/O/BMT population will have shorter hospital length of stay (LOS) and attributable LOS (ALOS) and therefore lower hospital costs.

Detailed Description
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The study team will compare hospital length of stay (LOS) and attributable length of stay (ALOS, the LOS attributable to CRI), in a randomized, un-blinded prospective trial utilizing short-dwell ethanol-lock therapy (ELT) (4 hours to 24 hour dwell times per day, repeated for up to 72 hours) placed within 24 - 36 hours of admission(Group 1, Preemptive ELT) versus ELT placed at the time of first positive blood culture report (Group 2, Rescue ELT (Standard of Care ). ELT will be given in both groups, in combination with systemic antibiotics, for the treatment of Catheter-related Infection (CRI) (suspected or proven) of the blood in children with central catheters. Participants will be enrolled from patients with hematologic/oncologic disorders and bone marrow or hematopoetic stem cell transplants admitted for care to Children's Hospital of Michigan (CHM), a tertiary care pediatric hospital in Detroit, Michigan. ALOS will be defined as the number of hospital days between first symptoms of CRI (or date of admission for those admitted with symptoms) and first negative blood culture. Aim 1: Compare two different treatment regimens for CRI using ELT (the preemptive ELT vs. standard of care) by way of a prospective, randomized, two-arm study. Study Hypothesis: The main hypothesis is that the short-dwell ethanol-lock therapy, defined above, placed within 24 - 36 hours of symptoms/admission (Arm 1) versus ELT placement at the time of first positive blood culture report (Arm 2), with concomitant systemic antibiotics, for the treatment of CRI (suspected or proven) of the blood in children with central catheters in the H/O/BMT population will have shorter hospital length of stay (LOS) and attributable LOS (ALOS) and therefore lower hospital costs. Aim 2: Compare sterilization rate of the infected intravascular device after ethanol-lock therapy (as defined by a negative blood culture obtained from the infected catheter 24 - 72 hours after ELT) and central catheter salvage rate after CRI using ELT in the two study arms. If the central catheter is salvaged for further clinical use, recurrence of infection with the same organism (re-infection) of the central catheter for 28 days from date of first ELT procedure will also be assessed. Aim 3: Assess tolerability and adverse effects of the ELT (safety). Aim 4: Perform sub-group analysis on the BSI episodes meeting National Healthcare Safety Network (NHSN) criteria for laboratory confirmed central line associated BSI (CLABSI) into the three categories of Criteria 1, 2 or 3 within the pediatric

Official Title
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Preemptive Ethanol Lock Therapy in Pediatric Hematology/Oncology Patients With Catheter Associated Bloodstream Infection: Impact on Length of Stay and Catheter Salvage

Conditions
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Leukemia, Lymphoma, Blood Disorders, Solid Tumors

Intervention / Treatment
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* Drug: Ethanol lock therapy (ELT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All children up to 21 years of age, with central catheters (any type) that develop symptoms and are admitted to CHM with an underlying H/O/BMT diagnosis for individual episodes of suspected or proven CRI of the blood, including rule out sepsis, will be screened for potential participation in this study. Individual CRI episodes in the same patient will be defined as a distinct central catheter associated blood stream infection if separated by greater than 28 days from prior ELT procedure and caused by a different organism identified on culture than the prior central catheter associated blood stream infection episode. Participants meeting study enrollment criteria will be offered participation and must have parental full informed consent, adolescent assent and young child verbal assent prior to enrollment as applicable. Exclusion Criteria: Children with documented allergy to ethanol or alcohol will be excluded. Blood cultures from patients that are reported positive for pathogen growth within 12 hours from the time they are obtained will be excluded from the study. Any patient at CHM with an infected central catheter and with another indwelling foreign body that communicates directly with the bloodstream, of which infection or colonization could not be excluded directly, will also be excluded from the study (i.e. Left Ventricular Assist Device) as it will not be possible to assess sterilization of the central catheter. Any patient with endocarditis or presumed endovascular infection will also be excluded. Any patient deemed critically ill or unstable, upon admission or during the early treatment course, in which case the treating clinician(s) feel that immediate line removal is potentially life-saving will be excluded from the study.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pre-emptive Ethanol Lock Therapy Group<br>Participants receive ethanol lock before blood cultures grow germ | Drug: Ethanol lock therapy (ELT)<br>* Participants will be randomized to receive early (preemptive) ELT (after 12 hours from time blood culture drawn, but before blood culture positive, R/O sepsis) with systemic antimicrobials versus standard ELT (placed in catheter when blood culture is positive for growth of a germ) with systemic antimicrobials.<br>* Other names: 70% Ethanol in water;|
| Active Comparator: Standard Ethanol Lock Therapy Group<br>Participants receive ethanol lock if and only after blood cultures grow germ | Drug: Ethanol lock therapy (ELT)<br>* Participants will be randomized to receive early (preemptive) ELT (after 12 hours from time blood culture drawn, but before blood culture positive, R/O sepsis) with systemic antimicrobials versus standard ELT (placed in catheter when blood culture is positive for growth of a germ) with systemic antimicrobials.<br>* Other names: 70% Ethanol in water;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of Stay (LOS) in Those With 14 Confirmed Catheter Related Infection Cases | A primary endpoint of this study is length of stay (LOS) per catheter infection episode/admission | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks | 
| Attributable Length of Stay (ALOS) in 14 Confirmed Catheter Related Infection Cases | TIME FROM FIRST POSITIVE TO FIRST NEGATIVE BLOOD CULTURE | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks | 
| Hospital COSTS in 14 Confirmed Catheter Related Infection Cases | Hospital COSTS | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Catheter Sterilization | Number of Catheters sterilized with interventions | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks | 
| Catheter Salvage | Number of Infected catheters (which achieved sterilization) with salvage for at least 14 days. | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks | 
| Number of Adverse Events Per Episode of Catheter Infection | Number of Adverse events per episode of distinct catheter infection that are thought to be related to the actual study intervention, namely timing of ethanol lock placement, will be reviewed and reported for each individual infection episode/admission. | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks but up to 1 month post the last ethanol dose administration | 
| Re-infection | Number of Re-Infected of salvaged catheters with same or new organism(s) within 28 days of prior CRI/ELT | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks but for up to 1 month total |