Central Line-Associated Bloodstream InfectionPhase 3NCT01472965
Ethanol Lock Therapy for Treatment and Secondary Prophylaxis of Central Line-Associated Bloodstream Infection
A Phase 3 study testing ethanol in people with Central Line-Associated Bloodstream Infection, run by St. Jude Children's Research Hospital at 2 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 6 months to 25 years
- Conditions the study is for
- Central Line-Associated Bloodstream Infection
- What is being tested?
- ethanol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 95 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 29 Dec 2011to 11 Nov 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Australia1 site
Royal Children's Hospital Melbourne
Parkville, Victoria, 3052
About this study
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
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.
Read the 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.
- Being tested
- ethanol, heparin-saline placebo
- Keywords
- central line, adolescents, children, bloodstream infection, antibiotic lock therapy, catheter lock therapy, ethanol lock therapy
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ethanolDrug
Also called 70% ethanol
70% ethanol catheter lock therapy
heparin-saline placeboDrug
Also called heparin-saline
heparin-saline placebo catheter lock therapy
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: heparin-saline placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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 cumulative incidence of therapeutic failure is reported.
Measured: Up to 25 weeks after the start of treatment
Cumulative Incidence of Relapse in Participants Receiving Standard Care Plus ELT vs. Standard Care Alone
Relapse was defined as new CLABSI with an identical organism occurring during the 24 week prophylaxis phase. The percentage of evaluable participants with relapse is reported.
Measured: Up to 25 weeks after the start of treatment
Cumulative Incidence of Reinfection in Participants Receiving Standard Care Plus ELT vs. Standard Care Alone
Reinfection was defined as new CLABSI with a different organism occurring during the 24 week prophylaxis phase. The percentage of evaluable participants with reinfection is reported.
Measured: 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
Occlusion was defined as central line occlusion or dysfunction requiring thrombolytic therapy. The percentage of evaluable participants requiring thrombolytic therapy for central line occlusion is reported.
Measured: Up to 26 weeks after the start of treatment.
Adverse Events in Participants Receiving Standard Care Plus ELT vs. Standard Care Alone
Adverse events attributable to lock therapy or related to the central venous access device (CVAD) were elicited from direct questioning at study visits and from the medical record. The percentage of evaluable participants with any potentially attributable adverse effect is reported.
Measured: Up to 37.5 weeks after the start of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2011 (estimated)
- Study start29 Dec 2011
- Primary completion11 Nov 2016
- Study completion11 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Central Line-Associated Bloodstream InfectionStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joshua Wolf, MBBS, BA, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01472965
- Sponsor's protocol ID
- ETHEL
- Status last verified
- Aug 2017
- First submitted
- 14 Nov 2011
- Last updated
- 13 Nov 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 29884572
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01472965
- Acronym / sponsor ID
- ETHEL
- Keywords
- central line, adolescents, children, bloodstream infection, antibiotic lock therapy, catheter lock therapy, ethanol lock therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 95 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Study start
- 29 Dec 2011 (actual)
- Primary completion
- 11 Nov 2016 (actual)
- Study completion
- 11 Nov 2016 (actual)
- First posted
- 17 Nov 2011 (estimated)
- Results
- Posted 13 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Active comparator | Drug: ethanolEligible 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. |
| Control | Placebo comparator | Drug: heparin-saline placeboEligible 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. |
Who may qualify
- Ages
- 6 months to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ethanolAlso: 70% ethanol70% ethanol catheter lock therapy | Drug | Treatment |
| heparin-saline placeboAlso: heparin-salineheparin-saline placebo catheter lock therapy | Drug | Control |
Primary outcome
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
Time frame: Up to 25 weeks after the start of treatment.
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.
5 secondary outcomes
Cumulative Incidence of Therapeutic Failure in Participants Receiving Standard Care Plus ELT vs. Standard Care Alone
Time frame: Up to 25 weeks after the start of treatment
Cumulative Incidence of Relapse in Participants Receiving Standard Care Plus ELT vs. Standard Care Alone
Time frame: Up to 25 weeks after the start of treatment
Cumulative Incidence of Reinfection in Participants Receiving Standard Care Plus ELT vs. Standard Care Alone
Time frame: 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
Time frame: Up to 26 weeks after the start of treatment.
Adverse Events in Participants Receiving Standard Care Plus ELT vs. Standard Care Alone
Time frame: Up to 37.5 weeks after the start of treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29884572Wolf 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.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joshua Wolf, MBBS, BA principal investigator
St. Jude Children's Research Hospital
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ethanol in people with Central Line-Associated Bloodstream Infection, run by St. Jude Children's Research Hospital at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Up to 25 weeks after the start of treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01472965, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2017.