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

NCT01472965 | Completed Phase 3 Results FDA Drug

• 1 other identifier: ETHEL
• Study Type: interventional
• Target: 95
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Central Line-Associated Bloodstream Infection

Keywords

central line; adolescents; children; bloodstream infection; antibiotic lock therapy; catheter lock therapy; ethanol lock therapy

Outcome Measures

Primary Outcomes (1)

• Percentage of Therapeutic Failures (Early or Late Failure) in Children and Adolescents With CLABSI Receiving Standard Care Plus Ethanol Lock Therapy (ELT) vs. Standard Care Alone

  Therapeutic failure was a pre-defined composite outcome comprising either 'early failure': central line removal, death, persistent positive blood cultures for \>72 hours, development of new CLABSI, or initiation of other ALT) during the 5 day treatment phase, or 'late failure': relapse (new CLABSI with an identical organism), or reinfection (new CLABSI with a different organism) during the 24 week prophylaxis phase. The percentage of evaluable participants with therapeutic failure is reported.

  Up to 25 weeks after the start of treatment.

Secondary Outcomes (5)

• Cumulative Incidence of Therapeutic Failure in Participants Receiving Standard Care Plus ELT vs. Standard Care Alone

  Up to 25 weeks after the start of treatment

• Cumulative Incidence of Relapse in Participants Receiving Standard Care Plus ELT vs. Standard Care Alone

  Up to 25 weeks after the start of treatment

• Cumulative Incidence of Reinfection in Participants Receiving Standard Care Plus ELT vs. Standard Care Alone

  Up to 25 weeks after the start of treatment.

• Rate of Central Venous Access Device (CVAD) Occlusion Events in Participants Receiving Standard Care Plus ELT vs. Standard Care Alone

  Up to 26 weeks after the start of treatment.

• Adverse Events in Participants Receiving Standard Care Plus ELT vs. Standard Care Alone

  Up to 37.5 weeks after the start of treatment.

Study Arms (2)

Treatment

ACTIVE COMPARATOR

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

Control

PLACEBO COMPARATOR

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

Interventions

ethanol DRUG

70% ethanol catheter lock therapy

Also known as: 70% ethanol

Treatment

heparin-saline placebo DRUG

heparin-saline placebo catheter lock therapy

Also known as: heparin-saline

Control

Eligibility Criteria

• Age: 6 Months - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (2)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Royal Children's Hospital Melbourne

Parkville, Victoria, 3052, Australia

Location

Related Publications (1)

• Wolf J, Connell TG, Allison KJ, Tang L, Richardson J, Branum K, Borello E, Rubnitz JE, Gaur AH, Hakim H, Su Y, Federico SM, Mechinaud F, Hayden RT, Monagle P, Worth LJ, Curtis N, Flynn PM. Treatment and secondary prophylaxis with ethanol lock therapy for central line-associated bloodstream infection in paediatric cancer: a randomised, double-blind, controlled trial. Lancet Infect Dis. 2018 Aug;18(8):854-863. doi: 10.1016/S1473-3099(18)30224-X. Epub 2018 Jun 5.

  PMID: 29884572 DERIVED

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Sepsis

Interventions

Ethanol

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals

Results Point of Contact

• Title: Joshua Wolf, MBBS, BA
• Organization: St. Jude Children's Research Hospital

joshua.wolf@stjude.org

901-595-1475

Study Officials

• Joshua Wolf, MBBS, BA

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2011
• First Posted: November 17, 2011
• Study Start: December 29, 2011
• Primary Completion: November 11, 2016
• Study Completion: November 11, 2016
• Last Updated: November 13, 2017
• Results First Posted: November 13, 2017

Record last verified: 2017-08

Locations

US (1); AU (1)