Preemptive Ethanol Lock Therapy in Pediatric Bloodstream Infection

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02095951

Enrollment

Registered

2014-03-26

Start date

2014-06-30

Completion date

2016-06-30

Last updated

2018-12-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Blood Disorders, Leukemia, Lymphoma, Solid Tumors

Brief summary

Detailed description

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

Interventions

DRUGEthanol lock therapy (ELT)

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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

6 Months to 21 Years

Healthy volunteers

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.

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Catheter Sterilization	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks	Number of Catheters sterilized with interventions
Re-infection	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks but for up to 1 month total	Number of Re-Infected of salvaged catheters with same or new organism(s) within 28 days of prior CRI/ELT
Catheter Salvage	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks	Number of Infected catheters (which achieved sterilization) with salvage for at least 14 days.
Number of Adverse Events Per Episode of Catheter Infection	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	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.

Countries

United States

Participant flow

Recruitment details

135 episodes screened, but only 36 initially met enrollment criteria. 27 unique patients were enrolled for 33 episodes (6 patients enrolled twice) of possible catheter infection.

Pre-assignment details

3 enrolled participants were removed from the study/analysis for failure to meet final enrollment criteria. Patient participants could be re-enrolled in the study more than once if their infection episodes (cases) were separated by at least 28 days.

Participants by arm

Arm	Count
Pre-emptive Ethanol Lock Therapy Group Study intervention group (Arm 1). Received Early Ethanol Lock Therapy before blood culture results were reported as positive or negative.	13
Standard Ethanol Lock Therapy Group Standard of Care Group (Arm 2) that received Ethanol Lock Therapy if and only if the blood culture was positive for growth of an organism.	14
Total	27

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	NO POSITIVE BLOOD CULTURE	9	6

Baseline characteristics

Characteristic	Pre-emptive Ethanol Lock Therapy Group	Standard Ethanol Lock Therapy Group	Total
Age, Categorical <=18 years	13 Participants	14 Participants	27 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	0 Participants	0 Participants	0 Participants
Region of Enrollment United States	13 participants	14 participants	27 participants
Sex: Female, Male Female	3 Participants	2 Participants	5 Participants
Sex: Female, Male Male	10 Participants	12 Participants	22 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 4	0 / 8
other Total, other adverse events	0 / 4	0 / 8
serious Total, serious adverse events	0 / 4	0 / 8

Outcome results

Primary

Attributable Length of Stay (ALOS) in 14 Confirmed Catheter Related Infection Cases

TIME FROM FIRST POSITIVE TO FIRST NEGATIVE BLOOD CULTURE

Time frame: Participants will be followed for the duration of hospital stay, an expected average of 2 weeks