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Taurolidine

Tunneled central venous catheters locked with Taurolock

Tunneled central venous catheter locked with heparin

When not in use the childrens tunneled central venous catheters are locked with the liquid Taurolock instead of heparin.

Taurolock

When not in use the childrens tunneled central venous catheters are locked with heparin

Henrik Schrøder, MD, Dr.med.

Children with cancer need a long term tunnelled central venous catheter (TCVC) for the entire duration of their treatment. TCVCs are locked with heparin when not in use. The most frequent complications of long term TCVC are catheter related blood steam infections. Taurolock is a new lock that is claimed to prevent the formation of luminal biofilm in TCVCs and has been demonstrated to eradicate infected CVCs. In this study the investigators will compare TCVCs locked with heparin with TCVCs locked with Taurolock. Hypothesis: Taurolock will diminish the number of CRBSI in children with cancer compared with children with heparin lock of their CVC.

The most frequent complications of long term TCVC are catheter related blood steam infections(CRBSI)often caused by microorganisms located in the biofilm formed on the inner surface of the TCVC after a short time. CRBSI may be lifethreatening, will need long term intravenous broad spectrum antibiotic therapy possibly combined with intraluminal antibiotic lock therapy. In spite of this CRBSI may often lead to the premature removal of the TCVC.

Several methods to prevent the occurrence of intraluminal microbial colonization have been investigated with no single method standing out as the optimal one.

There is a need for a simple and safe method of reducing the occurrence of CRBSI in immunocompromised children receiving chemotherapy for malignant diseases. Various catheter lock solutions in stead of using heparin have been investigated in experimental models. Taurolidine is a chemically modified amino acid with broad spectrum antimicrobial activity in vitro. It is claimed to prevent the formation of luminal biofilm in TCVCs in a CVC model and it has been demonstrated to eradicate infected CVC in a three reports with a total of 18 patients.

In a 24 months study of routine use of Taurolidine 1,25%/Sodium-Citrate 4% (TaurolockTM) a reduction of gram-positive CVC associated infections was demonstrated. The findings were not statistically significant due to relatively few patients.

There is a need of a larger study with more patients receiving Taurolock for locking the TCVC between use in order to test for a significant reduction of the occurrence of CRBSI. Furthermore there is a need for an in vivo demonstration of the reduction of biofilm formation in TCVCs locked with taurolock compared with TCVCs locked with heparin.

Taurolidine Lock Solution in the Prevention of Catheter Related Bacteremia

A Randomised Study of Taurolock for the Locking of Tunneled Central Venous Catheters in Children With Malignant Diseases.

Danish Child Cancer Foundation

TauroPharm

Aarhus University Hospital

MD, PhD

Catheter-Related Infections

Other Dietary Supplements

Citric Acid

Sodium Citrate

Anti-Infective Agents, Local

Citrate

At the beginning of each course of IV anti-tumor treatment, a nurse removes the lock TauroLock ™ and makes rinsing the CVC. At the end of each course, she rinses again the CVC and instills TauroLock ™ solution. Patients will be followed for each treatment, according to the same rhythm of their anti-tumor treatment program up to the end of the study

At the beginning of each course of IV anti-tumor treatment, a nurse makes rinsing the CVC. At the end of each course, she rinses again the CVC. Patients will be followed for each treatment, according to the same rhythm of their anti-tumor treatment program up to the end of the study

saline solution

Raffaele LONGO, MD

The purpose of this study is to compare the efficacy of a lock taurolidine-citrate solution vs standard saline solution for primary prevention of central venous catheter-associated bloodstream infection in adult patients treated with intra-venous therapy for a solid tumor

The central venous catheter (CVC)-associated bloodstream infection (CLABSI) represent a serious and persistent health problem in cancer patients with an implantable CVC receiving an intravenous (IV) anti-tumor therapy. The CLABSI include the CVC-associated bacteremia and the negative bloodstream local or generalized infections. CLABSI significantly increase morbidity and hospital costs. They can lead also to discontinuation of IV anti-tumor treatment, a severe sepsis, a septic shock or a death. Microbial colonization and biofilm development, which are resistant to antibiotic therapy, often lead to CVC replacement. CLABSI prevention is a key measure to improve clinical outcomes, particularly in patients at high risk. For this reason, CLABSI prevention is a national priority of the healthcare program. Taurolidine \[bis-(1,1-dioxoperhydro-1,2,4-thiadiazinyl-4) methane\] is an antimicrobial agent which kills and inhibits a wide range of micro-organisms in vitro, including multidrug resistant bacteria. A catheter lock solution was developed containing 1.35% taurolidine and 4% citrate. Due to the anti-adhesion activity of the taurolidine and anti-thrombotic properties of the citrate, this lock solution can disrupt bacterial adhesion to the inner surface of the implantable CVC preventing the production of biofilm. This lock solution showed a substantial reduction in the formation of biofilm and bacterial colonization of the inner surface of the implantable CVC is several prospective trials.

In a study of pediatric cancers receiving IV anti-tumor treatment, the use of a lock solution of taurolidine-citrate resulted in a reduction of Gram-positive CLABSI as compared to a control group of patients treated with a standard heparin lock solution. In another study of 71 pediatric patients, taurolidine-citrate solution reduced CLABSI compared with heparin (0.3 vs 1.3 infections per 1000 catheter-days, p: 0.03). Microbial colonization was found in 25.4% of the catheters. Regarding the toxicity, 7 patients only in the taurolidine-citrate group (20%) experienced side effects, the most being nausea, vomiting and abnormal sensations of taste.

Some clinical trials have also demonstrated the efficacy of taurolidine-citrate in terms of CLABSI reduction in patients on home total parenteral nutrition and in hemodialysis patients.

According to the French guidelines, an anti-bacterial lock therapy (preferably taurolidine) may be used as prevention in patients at increased risk of serious CLABSI complications. However, the effectiveness of the lock taurolidine-citrate solution for adult patients with solid tumors receiving an anti-tumor treatment via a totally implantable CVC is actually unknown and it remains to be assessed.

PRIMARY OBJECTIVE

- To compare the efficacy of a lock taurolidine-citrate solution vs standard saline solution for primary prevention of CLABSI in adult patients treated with IV anti-tumor therapy for a solid tumor.

SECONDARY OBJECTIVES

* To compare the impact of CLABSI in the 2 groups in terms of days of hospitalisation, delay of IV anti-tumoral treatment, costs of CVC removal and CLABSI-management
* To evaluate the adverse effects of the lock taurolidine-citrate solution in adult patients receiving an IV anti-tumor therapy for solid tumor PRIMARY ENDPOINT: Incidence rates of CLABSI per 1000 catheter-days

SECONDARY ENDPOINTS

* Days of CLABSI-related hospitalisation
* Anti-tumor treatment CLABSI-related delay
* Total CVC-removal for CLABSI
* Costs associated with the CLABSI management in the perspective of health insurance
* Evaluation of the taurolidine-citrate solution-related adverse effects

METHODOLOGY

* Single-center prospective, randomized, open-label, controlled, clinical phase IV trial
* 1:1 randomization

Stratification:

* Metastatic vs (neo) adjuvant
* Age ≤ 70 years vs \> 70 years

PROCEDURES During a standard clinical visit for IV anti-tumor treatment administration, the investigator informs the patient of the study procedures and check the eligibility criteria. At the beginning of the next cure, he collects his informed consent and performs randomisation. The patient is then included in the TauroLock ™ or saline arm.

At the beginning of each course, a nurse removes the lock TauroLock ™ and / or makes rinsing the CVC. At the end of each course, she rinses again the CVC and instills TauroLock ™ solution for patients in the TauroLock ™ arm. Patients will be followed for each treatment, according to the same rhythm of their anti-tumor treatment program up to the end of the study: the end of the IV anti-tumor treatment, the CVC removal for mechanical reasons or a CLABSI.

A follow-up visit will be performed 7-30 days after the study end.

PATIENTS NUMBER Based on surveillance data of nosocomial infections at our institution, the incidence of CLABSI in the control group is expected to about 3 per 1000 catheter-days.

Assuming that the use of TauroLock ™ will reduce at least this rate by three (expected 1 per 1000 in the treated group rate), which is consistent with literature data, 9785 days must be followed in each group (α and β risk at 5% and 10%, respectively).

Considering a mean follow-up of 4 months, we need for 81 patients pour any treatment group, 162 patients for the 2 groups.

TRIAL TIME

Duration of the inclusion period:

- 6 months

Duration of participation for each patient:

- Duration of IV anti-tumor treatment + 1 month of follow-up

STATISTICAL ANALYSIS Verification of the homogeneity of the groups for major confounding factors: WHO performance status, indication for anti-tumor treatment (metastatic vs (neo)-adjuvant cancer), age, duration of follow-up, type of anti-tumor treatment (weekly, every 15 or 21 days) and type of hospitalisation (full vs day-hospital). Qualitative variables will be compared between the 2 groups by Chi-square test or Fisher exact test if the normality conditions are not met. Quantitative variables are compared by Student's t test or non parametric Wilcoxon test if the normality conditions are not met.

Primary endpoint: the incidence of CLABSI will be compared between groups by a logistic regression test with adjustment for stratification and confounding factors, if necessary.

Secondary endpoints: the qualitative criteria will be compared between the 2 groups by Chi-square test or Fisher exact test if the conditions of normality are not met. The quantitative criteria will be compared by Student's t test or non parametric Wilcoxon test if the conditions of normality are not met.

The α risk is set at 5%.

EXPECTED BENEFITS The expected benefits are a direct reduction of CLABSI for adult cancer patients receiving IV anti-tumor treatment via a CVC leading to a direct reduction of morbidity and mortality. In addition, a better control of CLABSI should allow a cost savings. A literature review by the Centers for Disease Control and Prevention (Atlanta, USA) estimated between $ 29,156 and 7288 the cost of CLABSI. Similarly, a report by the Institute for Research and Documentation in Health Economics (IRDES), based on the PMSI (Program of medicalization of information systems) data, estimated that CLABSI entailed an additional cost of € 10,950 (+ / - 1690) and a extending of the hospitalisation of 14.7 days (+ / - 1.84). Finally, a reduction of the CLABSI should globally lead to a less use of antibiotics and to a consequently reduced probability of resistant organisms selection.

QUALITY ASSURANCE PLAN Data will be recorded in a paper case report form from medical records.

The accuracy and completeness of data will be monitored by a study coordinator :

* 100% inform consent, eligibility criteria and safety data
* 20% data recorded in CRF (case report form) Data will be registered in Microsoft Office ACCESS 2003 Base. It's a single-center study so thre're no special procedures to address registry operations and analysis activities. Safety data like reporting for adverse event will be made by fax with The CRPV (centre régional de pharmacovogilance de Nancy).

The security of the data transfer is assured by the french "Méthodologie de Référence MR001" (Comission Nationale Informatique et Liberté).

ATAPAC Study (TauroLock Activity in Adult Cancer Patients)

Prospective, Randomized, Controlled Trial Evaluating the Efficacy of a Lock-therapy With a Solution of Taurolidine/Citrate (TauroLock) vs Standard Saline Solution for the Primary Prevention of Catheter-related Infections (CLI) in Adult Patients Wtih a Non-hematological Cancer Treated With Intravenous Anti-tumor Therapy

incidence rates of CLABSI per 1000 catheter-days

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Taurolidine Lock Solution in the Prevention of Catheter Related Bacteremia	NCT00735813	Bacteremia Neoplasms	Taurolock Heparin	- 17 Years	Aarhus University Hospital
ATAPAC Study (TauroLock Activity in Adult Cancer Patients)	NCT02279121	Catheter-Relate...	Taurolock saline solution	18 Years -	Centre Hospitalier Régional Metz-Thionville
Taurolidine Lock Solution in the Prevention of Catheter Related Bacteremia	NCT00735813	Bacteremia Neoplasms	Taurolock Heparin	- 17 Years	Aarhus University Hospital

Spots Global Cancer Trial Database for taurolock

Every month we try and update this database with for taurolock cancer trials from around the world to help patients and their families find trials that might be right for them.
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Spots Global Cancer Trial Database for taurolock

Every month we try and update this database with for taurolock cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for taurolock cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.