Pediatric Ethanol Lock Therapy Study.

Study Overview
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Brief Summary
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This study is a double-blind crossover design to compare prophylaxis with ethanol lock therapy versus placebo lock therapy (heparin). The primary outcome measure will be the number of catheter related blood stream infections (CRBSI) in each time period.

Detailed Description
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Central venous catheters (CVCs) are crucial for patients who require long term vascular access due to a variety of underlying diseases. Children with intestinal insufficiency and other diseases require vascular access to receive total parenteral nutrition, chemotherapy, fluid support and for the convenience of avoiding peripheral sticks when multiple blood draws are required. While these catheters have many benefits, they are also associated with complications such as catheter-related bloodstream infections (CRBSI). These infections can be a major cause of morbidity, mortality, and increased health care costs. Coagulase-negative staphylococci, Staphylococcus aureus, aerobic gram-negative bacilli, and Candida species (especially albicans) are the most common organisms responsible for these infections. These infections are traditionally treated with systemic antimicrobial therapy. There are times when the catheter must be removed to adequately treat the infection, however, indications for catheter removal in children are controversial. For some children with a history of multiple line infections, there are limited sites available to place new vascular access when the CVC needs to be replaced. Reducing the number of infections in this group of children is highly desirable. The goal of this study is to improve patient outcomes by reducing the risk of infection, thereby decreasing waitlist morbidity and mortality and improving post transplant care. Lock therapy is the procedure of allowing medications to dwell in the line for extended periods of time without interruption. Many different agents such as ethanol, vancomycin and gentamicin have been used successfully as a means to salvage a CVC that has become infected. There is limited information regarding the use of lock therapy to prevent CRBSI in patients with CVCs. However, in patients with a history of multiple CRBSI, who have a critical need to maintain vascular access, lock therapy with a solution of 25% ethanol has been suggested to prevent future CRBSI. There is sufficient data to suggest that this combination is likely to be effective, is unlikely to lead to the development of multidrug resistant organisms and is well tolerated. Our hypothesis is that the use of ethanol as a lock therapy can reduce the number of CRBSI in both pre and post transplant patients with intestinal insufficiency. Specific Aim: To compare the number of CRBSI in patients who receive ethanol lock therapy with the number of infections while on placebo lock therapy with heparin. This will be accomplished by conducting a prospective cross-over, double blind, placebo controlled study in children who have intestinal insufficiency and a history of multiple CRBSIs. Each child will receive 3 months of study lock therapy (25% ethanol) and 3 months of placebo lock therapy (heparin). The investigators, the patient and their family will be blinded to the treatment. The primary outcome measure will be the number of CRBSIs. Patients will also be observed for possible side effects from the therapy, and the need for line removal. This pilot study should provide preliminary data and information regarding the feasibility for a larger, multi-center study of ethanol lock therapy for the prevention of CRBSI.

Official Title
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Ethanol Lock Therapy for the Prevention of Catheter Related Blood Stream Infections

Conditions
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Catheter-Related Infections

Intervention / Treatment
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* Drug: 25% ethanol
* Other: heparin lock


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: patients with central venous access and a history of three or more CRBSI in the prior 6 months age greater than 6 months anticipation for the need for continued central venous access over the next 7 months availability to come for a monthly study visit anticipation that the patient will receive medical care at Children's Hospital of Pittsburgh for the majority of the CRBSI which occur during the next 7 months and the ability to lock the central venous catheter for a minimum of 4 hours per day Exclusion criteria: age less than 6 months and greater than or equal to 21 years known immunodeficiency (with the exception of immunosuppression in a patient after organ transplantation) known allergy or intolerance to ethanol or heparin lock therapy

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>25% ethanol for 12 weeks; wash out period for 4 weeks; heparin lock for 12 weeks | Drug: 25% ethanol<br>* Study Lock -25% Ethanol- The ethanol lock therapy consists of placing up to 2.3 ml of 25% ethanol into the central venous catheter and allowing it to dwell for 4 to 12 hours per day.<br>* Other names: ethanol;Other: heparin lock<br>* Placebo Lock - Heparin - These will be prepared in a sterile fashion in the Pharmacy of Children's Hospital of Pittsburgh in 10 day supplies as 1ml lock syringes utilizing 100 units/ml if the central venous catheter is accessed once daily and 10 units/ml if accessed more than once daily. The lock solution will be instilled and allowed to dwell for 4 to 12 hours.<br>|
| Experimental: Group 2<br>heparin lock for 12 weeks; wash out period for 4 weeks; 25% ethanol lock for 12 weeks | Drug: 25% ethanol<br>* Study Lock -25% Ethanol- The ethanol lock therapy consists of placing up to 2.3 ml of 25% ethanol into the central venous catheter and allowing it to dwell for 4 to 12 hours per day.<br>* Other names: ethanol;Other: heparin lock<br>* Placebo Lock - Heparin - These will be prepared in a sterile fashion in the Pharmacy of Children's Hospital of Pittsburgh in 10 day supplies as 1ml lock syringes utilizing 100 units/ml if the central venous catheter is accessed once daily and 10 units/ml if accessed more than once daily. The lock solution will be instilled and allowed to dwell for 4 to 12 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Episodes of Catheter Related Blood Stream Infections in Each Study Period. | For the purpose of this study, episodes of catheter related blood stream infections were considered as the primary outcome measure. An episode of infection was defined as more than one positive blood culture obtained from the catheter requiring antibiotic therapy. Each episode after enrollment was recorded in its appropriate study period: ethanol lock, placebo lock, or washout period. If a patient had a catheter related blood stream infections, the study locks were held until after the number of days in each period was calculated as the number of days not on antibiotic therapy. | 7 months per study patient | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, Side Effects | collection of adverse events and safety information. Each participant was contacted either at a clinical visit or by phone every two weeks while enrolled in the study. | 7 months per study patient | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intestinal insufficiency, central venous catheter, Catheter-Related Infections, pediatrics, ethanol