Preemptive Ethanol Lock Therapy in Pediatric Bloodstream Infection

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02095951
• Other study ID #: 2024.11
• Status: Completed
• Phase: Phase 4
• Start date: June 2014
• Est. completion date: June 2016

Study information

• Verified date: August 2018
• Source: Children's Hospital of Michigan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 21 Years

Eligibility

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.

Related Conditions & MeSH terms

• Blood Disorders
• Hematologic Diseases
• Leukemia
• Lymphoma
• Solid Tumors

Intervention

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.

Locations

Country	Name	City	State
United States	Children's Hospital of Michigan	Detroit	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital of Michigan	Blue Cross Blue Shield of Michigan Foundation

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

McGrath E, Du W, Rajpurkar M. Preemptive Ethanol Lock Therapy in Pediatric Hematology/Oncology Patients With Catheter-Associated Bloodstream Infection: Impact on Length of Stay, Cost, and Catheter Salvage. Clin Pediatr (Phila). 2018 Mar;57(3):285-293. doi — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Catheter Sterilization	Number of Catheters sterilized with interventions	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks
Secondary	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
Secondary	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
Secondary	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