Preemptive Ethanol Lock Therapy in Pediatric Bloodstream Infection

• Sponsor: Children's Hospital of Michigan (Other)
• Overall Status: Completed
• CT.gov ID: NCT02095951
• Collaborator: Blue Cross Blue Shield of Michigan Foundation (Other)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 24
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Lymphoma; Blood Disorders; Solid Tumors	Drug: Ethanol lock therapy (ELT)	Phase 4

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Preemptive Ethanol Lock Therapy in Pediatric Hematology/Oncology Patients With Catheter Associated Bloodstream Infection: Impact on Length of Stay and Catheter Salvage
• Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pre-emptive Ethanol Lock Therapy Group Participants receive ethanol lock before blood cultures grow germ	Drug: Ethanol 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.; Other Names: 70% Ethanol in water
Active Comparator: Standard Ethanol Lock Therapy Group Participants receive ethanol lock if and only after blood cultures grow germ	Drug: Ethanol 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.; Other Names: 70% Ethanol in water

Outcome Measures

Primary Outcome Measures

1. 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

2. 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

3. 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 Outcome Measures

1. Catheter Sterilization [Participants will be followed for the duration of hospital stay, an expected average of 2 weeks]

   Number of Catheters sterilized with interventions

2. 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.

3. 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.

4. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Michigan	Detroit	Michigan	United States	48201

Sponsors and Collaborators

• Children's Hospital of Michigan
• Blue Cross Blue Shield of Michigan Foundation

Investigators

• Principal Investigator: Eric J McGrath, MD, Wayne State University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Chaudhary M, Bilal MF, Du W, Chu R, Rajpurkar M, McGrath EJ. The impact of ethanol lock therapy on length of stay and catheter salvage in pediatric catheter-associated bloodstream infection. Clin Pediatr (Phila). 2014 Oct;53(11):1069-76. doi: 10.1177/0009922814533591. Epub 2014 May 7.
• McGrath EJ, Salloum R, Chen X, Jiang Y, Boldt-MacDonald K, Becker C, Chu R, Ang JY. Short-dwell ethanol lock therapy in children is associated with increased clearance of central line-associated bloodstream infections. Clin Pediatr (Phila). 2011 Oct;50(10):943-51. doi: 10.1177/0009922811409568. Epub 2011 May 27.
• Rajpurkar M, McGrath E, Joyce J, Boldt-MacDonald K, Chitlur M, Lusher J. Therapeutic and prophylactic ethanol lock therapy in patients with bleeding disorders. Haemophilia. 2014 Jan;20(1):52-7. doi: 10.1111/hae.12241. Epub 2013 Aug 1.

• Responsible Party: Eric McGrath, Assistant Professor of Pediatrics - Clinical, Children's Hospital of Michigan
• ClinicalTrials.gov Identifier: NCT02095951
• Other Study ID Numbers: 2024.11
• First Posted: Mar 26, 2014
• Last Update Posted: Dec 19, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Sepsis; Hematologic Diseases; Ethanol

Study Results

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 Detail	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.

Arm/Group Title	Pre-emptive Ethanol Lock Therapy Group	Standard Ethanol Lock Therapy Group
Arm/Group Description	Study intervention group (Arm 1). Received Early Ethanol Lock Therapy before blood culture results were reported as positive or negative.	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.
Period Title: Overall Study
STARTED	13	14
COMPLETED	4	8
NOT COMPLETED	9	6

Baseline Characteristics

Arm/Group Title	Pre-emptive Ethanol Lock Therapy Group	Standard Ethanol Lock Therapy Group	Total
Arm/Group Description	Study intervention group (Arm 1). Received Early Ethanol Lock Therapy before blood culture results were reported as positive or negative.	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.	Total of all reporting groups
Overall Participants	13	14	27
Age (Count of Participants)
<=18 years	13 100%	14 100%	27 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	3 23.1%	2 14.3%	5 18.5%
Male	10 76.9%	12 85.7%	22 81.5%
Region of Enrollment (participants) [Number]
United States	13 100%	14 100%	27 100%

Outcome Measures

1. Primary Outcome

Title	Length of Stay (LOS) in Those With 14 Confirmed Catheter Related Infection Cases
Description	A primary endpoint of this study is length of stay (LOS) per catheter infection episode/admission
Time Frame	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks

Outcome Measure Data

Analysis Population Description

1 participant with 2 distinct episodes of catheter infection was enrolled twice in each group.

Arm/Group Title	Pre-emptive Ethanol Lock Therapy Group	Standard of Care Ethanol Lock Therapy Group
Arm/Group Description	Pre-emptive Ethanol Lock Therapy Group	Standard of Care Ethanol Lock Therapy group
Measure Participants	4	8
Measure Catheter Infection Episodes (cases)	5	9
Mean (Standard Deviation) [HOURS]	124 (51)	208 (151)

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

1 participant with 2 distinct episodes of catheter infection was enrolled twice in each group.

Arm/Group Title	Pre-emptive Ethanol Lock Therapy Group	Standard Ethanol Lock Therapy Group
Arm/Group Description	Study Arm, given pre-emptive ELT	Study Arm, given standard of care
Measure Participants	4	8
Measure Catheter Infection Episodes (cases)	5	9
Mean (Standard Deviation) [HOURS]	21 (20)	32 (12)

3. Primary Outcome

Title	Hospital COSTS in 14 Confirmed Catheter Related Infection Cases
Description	Hospital COSTS
Time Frame	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks

Outcome Measure Data

Analysis Population Description

1 participant with 2 distinct episodes of catheter infection was enrolled twice in each group.

Arm/Group Title	Pre-emptive Ethanol Lock Therapy Group	Standard Ethanol Lock Therapy Group
Arm/Group Description	Study Arm, given pre-emptive ELT	Study Arm, given standard of care
Measure Participants	4	8
Measure Catheters	5	9
Mean (Standard Deviation) [USD $]	11,441 (3722)	18,071 (3739)

4. Secondary Outcome

Title	Catheter Sterilization
Description	Number of Catheters sterilized with interventions
Time Frame	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks

Outcome Measure Data

Analysis Population Description

1 participant with 2 distinct episodes of catheter infection was enrolled twice in each group.

Arm/Group Title	Pre-emptive Ethanol Lock Therapy Group	Standard Ethanol Lock Therapy Group
Arm/Group Description	Study Arm, given pre-emptive ELT	Study Arm, given standard of care
Measure Participants	4	8
Measure Catheters	5	9
Number [Catheters]	5	9

5. Secondary Outcome

Title	Catheter Salvage
Description	Number of Infected catheters (which achieved sterilization) with salvage for at least 14 days.
Time Frame	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks

Outcome Measure Data

Analysis Population Description

1 participant with 2 distinct episodes of catheter infection was enrolled twice in each group.

Arm/Group Title	Pre-emptive Ethanol Lock Therapy Group	Standard Ethanol Lock Therapy Group
Arm/Group Description	Study intervention group (Arm 1). Received Early Ethanol Lock Therapy before blood culture results were reported as positive or negative.	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.
Measure Participants	4	8
Measure Catheters	5	9
Number [Catheters]	5	9

6. Secondary Outcome

Title	Number of Adverse Events Per Episode of Catheter Infection
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

1 participant with 2 distinct episodes of catheter infection was enrolled twice in each group.

Arm/Group Title	Pre-emptive Ethanol Lock Therapy Group	Standard Ethanol Lock Therapy Group
Arm/Group Description	Study intervention group (Arm 1). Received Early Ethanol Lock Therapy before blood culture results were reported as positive or negative.	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.
Measure Participants	4	8
Measure Catheter Infection Episodes (cases)	5	9
Number [Adverse Events]	0	0

7. Secondary Outcome

Title	Re-infection
Description	Number of Re-Infected of salvaged catheters with same or new organism(s) within 28 days of prior CRI/ELT
Time Frame	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks but for up to 1 month total

Outcome Measure Data

Analysis Population Description

1 participant with 2 distinct episodes of catheter infection was enrolled twice in each group.

Arm/Group Title	Pre-emptive Ethanol Lock Therapy Group	Standard Ethanol Lock Therapy Group
Arm/Group Description	Study intervention group (Arm 1). Received Early Ethanol Lock Therapy before blood culture results were reported as positive or negative.	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.
Measure Participants	4	8
Measure Catheters	5	9
Number [Catheters]	0	0

Adverse Events

Time Frame	Each participant was assessed for Adverse Events for up to 30 days post ELT receipt. (1 participant with 2 distinct episodes of catheter infection was enrolled twice in each group.)
Adverse Event Reporting Description	Elevation of ALT, AST from baseline; CVC line breakage, malfuntion, or thrombosis; Reinfection of line within 14 days after line.
Arm/Group Title	Arm 1		Arm 2
Arm/Group Description	Study Arm, given pre-emptive ELT		Study Arm, given standard of care
All Cause Mortality
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/8 (0%)
Serious Adverse Events
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/8 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.