Central Line-associated Bloodstream Infection Prevention Using TauroLock-Hep100 in Pediatric Oncology Patients

Tunneled central venous access devices (CVAD) are fundamental in pediatric oncology for long-term venous access. The incidence of central line-associated bloodstream infections (CLABSI) is high. In the Princess Máxima Center, the incidence rate of CLABSI is 1.51 per 1,000 CVAD-days, CLABSIs are seen in at least 30% of the children with a CVAD, 17% of the inserted CVADs are removed early and 5% of the patients are admitted at an intensive care unit due to CLABSIs. Central venous thrombosis (CVT) is another severe complication of a CVAD, with an incidence rate of 0.02-0.24 per 1,000 CVAD-days. After a review of the literature, we concluded that the taurolidine-citrate(-heparin) lock solution (TCHL) is the most promising method for the prevention of CLABSIs and CVTs. In the Netherlands, the heparin lock (HL) is the standard of care. The HL however, does not have an antimicrobial activity and its use is barely supported by literature. The TCHL has anticoagulant and antimicrobial activities without reported resistance to taurolidine. The TCHL has shown to decrease the CVAD-infection incidence by 27-100% in hemodialysis, total parenteral nutrition, and adult oncology patients. In pediatric oncology patients, six studies have been performed. Unfortunately, these studies did not deliver enough evidence to implement the TCHL in pediatric oncology patients, mainly due to the small study groups, n-total ≤ 180. Therefore, we want to perform an open labelled RCT in a large patient group (n=462) so that we can finally draw conclusions on the efficacy and safety of the TCHL in pediatric oncology patients. Our goal is to increase the quality of life for children with cancer by reducing the CLABSI-rate, CVAD-removal rate, dispense of antibiotics, days of hospital/intensive care admission, and mortality rate due to CLABSI.

A decrease in the incidence of central line-associated bloodstream infections in the investigational study group, compared to the control group.

Every CVAD will be followed up until first tunneled CLABSI episode has been resolved (symptom free and/or negative blood cultures), removal of the CVAD, or death of the patient, whatever end-point will come first with a maximum study period of 90 days.

Patients in the taurolidine, citrate and heparin lock study arm will receive a lock solution containing taurolidine 1.35%, citrate 4% and heparin 100 IU/ml (TauroLock™-Hep100). Patients in the heparin lock study arm will receive a lock solution containing the standard of care heparin 100 IU/ml. The lock volume will depend on the central venous access device type, the central venous access device (CVAD) lumen needs to be filled completely. The locks will be instilled with a minimum of once every three weeks, and a maximum of once every week. The study locks will be aspirated before manipulation of the CVAD.