Ethanol Lock Therapy for Treatment and Secondary Prophylaxis of Central Line-Associated Bloodstream Infection

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by St. Jude Children's Research Hospital
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT01472965
First received: November 14, 2011
Last updated: May 21, 2014
Last verified: May 2014
  Purpose

Use of long-term central venous access devices (including tunneled lines and ports) can be associated with development of bloodstream infection caused by build-up of bacteria or fungus on the inside of the device, called central line associated bloodstream infection (CLABSI). This infection generally requires hospital admission and antibiotic therapy. This treatment usually helps eradicate the infection but sometimes it is not possible to clear or it comes back after treatment. Also, once someone has had one line infection the chance of getting another one is higher. This study will test whether treatment and secondary prophylaxis of CLABSI with ethanol lock therapy (ELT) can significantly reduce the risk of treatment failure (comprising failure to clear initial infection, relapse or reinfection) in children and adolescents treated for cancer or hematologic disorders or undergoing hematopoietic stem cell transplantation (HSCT). ELT involves injecting a solution of ethanol and water into the line or port, allowing it to dwell for 2 hours, and then withdrawing the solution.


Condition Intervention Phase
Central Line-Associated Bloodstream Infection
Drug: ethanol
Drug: heparin-saline placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Double-Blind, Randomized, Placebo-Controlled, Trial of Ethanol Lock Therapy for Treatment and Secondary Prophylaxis of Central Line Associated Bloodstream Infection (CLABSI) in Children and Adolescents

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Proportion of therapeutic failures (early or late failure) in children and adolescents with CLABSI receiving standard care plus ELT [ Time Frame: Up to 25 weeks after the start of treatment. ] [ Designated as safety issue: No ]
  • Proportion of therapeutic failures (early or late failure) in children and adolescents with CLABSI receiving standard care alone [ Time Frame: Up to 25 weeks after the start of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cumulative incidence of therapeutic failure in participants receiving standard care plus ELT [ Time Frame: Up to 37.5 weeks after the start of treatment ] [ Designated as safety issue: No ]
  • Cumulative incidence of therapeutic failure in participants receiving standard care alone [ Time Frame: Up to 37.5 weeks after the start of treatment ] [ Designated as safety issue: No ]
  • Cumulative incidence of relapse in participants receiving standard care plus ELT [ Time Frame: Up to 37.5 weeks after the start of treatment ] [ Designated as safety issue: No ]
  • Cumulative incidence of relapse in participants receiving standard care alone [ Time Frame: Up to 37.5 weeks after the start of treatment. ] [ Designated as safety issue: No ]
  • Cumulative incidence of reinfection in participants receiving standard care plus ELT [ Time Frame: Up to 37.5 weeks after the start of treatment. ] [ Designated as safety issue: No ]
  • Cumulative incidence of reinfection in participants receiving standard care alone [ Time Frame: Up to 37.5 weeks after the start of treatment. ] [ Designated as safety issue: No ]
  • Rate of CVAD occlusion events in participants receiving standard care plus ELT [ Time Frame: Up to 37.5 weeks after the start of treatment. ] [ Designated as safety issue: No ]
  • Rate of CVAD occlusion events in participants receiving standard care alone [ Time Frame: Up to 37.5 weeks after the start of treatment. ] [ Designated as safety issue: No ]
  • Adverse events in participants receiving standard care plus ELT [ Time Frame: Up to 37.5 weeks after the start of treatment. ] [ Designated as safety issue: No ]
  • Adverse events in participants in participants receiving standard care alone [ Time Frame: Up to 37.5 weeks after the start of treatment. ] [ Designated as safety issue: No ]

Estimated Enrollment: 138
Study Start Date: December 2011
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Treatment
Eligible patients with CLABSI will be enrolled within 96 hours of collection of positive blood culture and randomized to blinded treatment with 70% ethanol catheter lock therapy.
Drug: ethanol
70% ethanol catheter lock therapy
Other Name: 70% ethanol
Placebo Comparator: Control
Eligible patients with CLABSI will be enrolled within 96 hours of collection of positive blood culture and randomized to blinded treatment with heparin-saline placebo catheter lock therapy.
Drug: heparin-saline placebo
heparin-saline placebo catheter lock therapy
Other Name: heparin-saline

Detailed Description:

Eligible patients with CLABSI will be enrolled within 96 hours of collection of positive blood culture and randomized to blinded treatment with 70% ethanol or heparin-saline placebo catheter lock therapy.

After enrollment, all subjects will receive catheter lock therapy for a 5 day Treatment Phase, followed by a 24 week Prophylaxis Phase. Participants in the active treatment arm will receive 70% ethanol locks and those in the placebo arm will receive heparin-saline placebo locks in identical fashion.

In addition to the study intervention, participants in both arms will receive standard systemic antibiotic therapy according to the preference of the ward clinician.

The intervention will continue for 24 weeks unless off-therapy criteria are met or the catheter is removed.

After the intervention is discontinued, participants will be monitored for 90 days, or 30 days after line removal, whichever is shorter. If the intervention is discontinued prior to 24 weeks due to adverse event or physician request, participants will be monitored for the remainder of the 24 week period.

Primary Objective:

  • To compare the proportion of therapeutic failures in children and adolescents with CLABSI during treatment with standard care plus Ethanol Lock Therapy (ELT) versus standard care alone.

Secondary Objectives:

  • To estimate and compare the cumulative incidence of CLABSI treatment failure, relapse or reinfection in children and adolescents receiving ELT plus standard care versus those receiving standard care alone.
  • To estimate the risk of central venous access device (CVAD) occlusion associated with the use of ELT plus standard care, compared with standard care alone, in children and adolescents.
  • To estimate the risk of adverse events possibly attributable to ELT associated with the use of ELT plus standard care, compared with standard care alone, in children and adolescents.
  Eligibility

Ages Eligible for Study:   6 Months to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects ≥6 months to < 25 years of age who are ≥5kg
  • New diagnosis (within 96 hours of collection of first positive blood culture) of CLABSI (participants with previous CLABSI will be eligible if not previously enrolled in the study)
  • Silicone CVAD in situ (ports, Hickman and Broviac lines will all be eligible)
  • Treating clinician plans to attempt salvage of CVAD
  • Participant is receiving treatment for cancer or any hematologic disorder or is receiving hematopoietic stem cell transplantation (HSCT) at a participating institution.

Exclusion Criteria:

  • Allergy to ethanol or components of placebo lock
  • Concomitant use of metronidazole, disulfiram or trabectedin
  • Plan to remove CVAD within 6 days
  • Continuous use of all lumens of CVAD leading to anticipated inability to lock each lumen for at least 2 hours per day
  • Known CVAD obstruction
  • Subjects who are capable of becoming pregnant will require an negative pregnancy test before entry to study
  • Use of ELT in the preceding 2 weeks
  • Expected survival <6 days
  • Proven alternative source of bloodstream infection (BSI), or clinical evidence of CVAD track or port-pocket infection
  • Multiple long-term CVADs in situ
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01472965

Contacts
Contact: Joshua Wolf, MBBS, BA 1-866-278-5833 info@stjude.org

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Joshua Wolf, MBBS, BA    866-278-5833    info@stjude.org   
Principal Investigator: Joshua Wolf, MBBS, BA         
Australia, Victoria
Royal Children's Hospital Melbourne Recruiting
Parkville, Victoria, Australia, 3052
Contact: Tom Connell, FRACP, PhD    61 3 9345 4859    tom.connell@rch.org.au   
Principal Investigator: Tom Connell, FRACP, PhD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Joshua Wolf, MBBS, BA St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01472965     History of Changes
Other Study ID Numbers: ETHEL
Study First Received: November 14, 2011
Last Updated: May 21, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
central line
adolescents
children
bloodstream infection
antibiotic lock therapy
catheter lock therapy
ethanol lock therapy

Additional relevant MeSH terms:
Communicable Diseases
Infection
Calcium heparin
Ethanol
Heparin
Anti-Infective Agents
Anti-Infective Agents, Local
Anticoagulants
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014