A Randomized, Double-Blind, Placebo-Controlled Trial (TAURCAT Study) of Citrate Lock Solution for Prevention of Endoluminal Central Venous Catheter Infection in Neutropenic Hematological Patients

Abstract

Infection of long-term central venous catheters (CVCs) remains a challenge in the clinical management of cancer patients. We aimed to determine whether a lock solution with taurolidine-citrate-heparin would be more effective than placebo for preventing nontunneled CVC infection in high-risk neutropenic hematologic patients. We performed a prospective, multicenter, randomized (1:1), double-blind, parallel, superiority, placebo-controlled trial involving 150 hematological patients with neutropenia carrying nontunneled CVCs who were assigned to receive CVC lock solution with taurolidine-citrate-heparin or heparin alone. The primary endpoint was bacterial colonization of the CVC hubs. Secondary endpoints were the incidence of catheter-related bloodstream infection (CRBSI), CVC removal, adverse events related to the lock solution, and the 30-day case fatality rate. CVC lock solution with taurolidine-citrate-heparin was associated with less colonization of the CVC hubs than that with placebo, with no statistically significant differences: 4.1%, versus 10.1% (relative risk [RR] = 0.41, 95% confidence interval [CI] = 0.11 to 1.52), with a cumulative incidence of 4.17 (95% CI = 0.87 to 11.70) and 10.14 (95% CI = 4.18 to 19.79), respectively. There were no significant differences regarding the secondary endpoints. Only three episodes of CRBSI occurred during the study period. No adverse events related to the administration of the lock solution occurred. In this trial involving high-risk patients carrying nontunneled CVCs, the use of taurolidine-citrate-heparin did not show a benefit over the use of placebo. Nevertheless, the safety of this prevention strategy and the trend toward less hub colonization in the taurolidine-citrate-heparin group raise the interest in assessing its efficacy in centers with higher rates of CRBSI. (This study has been registered in ISRCTN under identifier ISRCTN47102251.)

The efficacy of taurolidine containing lock solutions for the prevention of central-venous-catheter-related bloodstream infections: a systematic review and meta-analysis

“…Fourteen articles (1219 patients) were included in the qualitative synthesis, nine (918 patients) of these articles were included in the quantitative synthesis. [57][58][59][60][61][62][63][64][65][66][67][68][69][70] [Figure 1]…”

“…Of the 14 included articles, five (36%) had a blinded study design, of which four had a double-blinded design. [61,[66][67][68][69] Two (14%) non-blinded studies used an assessor-masked design to avoid bias. [62,64] The 14 included articles described patients receiving haemodialysis (n=5, 36%) or TPN (n=4, 29%), oncology patients (n=4, 29%), or a combination of these (n=1, 7%).…”

Central venous catheter–related infections in hematology and oncology: 2020 updated guidelines on diagnosis, management, and prevention by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)

“…Heparin lock solutions are commonly used, although saline solution might be a safe alternative as it proved non-inferior in terms of functional problems and CVC-related bacteremia in a randomized trial including 802 cancer patients with totally implantable venous access devices [181]. Taurolidinecitrate-heparin did not result in significantly less CVC hub colonization and CRBSI than placebo in neutropenic hematologic patients in a prospective multicenter trial involving 150 patients with non-tunneled CVCs [182]. Ethanol 70% lock solution has been studied in several randomized trials including heterogenous study populations with conflicting results.…”

Understanding and Managing Sepsis in Patients With Cancer in the Era of Antimicrobial Resistance

“…There are several current studies evaluating the prevalence, clinical features, etiology, and outcomes of cancer patients with bacteremia, with reported rates of septic shock varying by series from 6 to 57% (11,13,15,(18)(19)(20). Nevertheless, very few investigations have focused on patients presenting with sepsis or septic shock (31,36,48,49,52,55,87,88), and among these, some were retrospective, some used different sepsis definitions, and some did not provide comprehensive data.…”

“…Of special concern is the widespread emergence and dissemination of multidrug-resistant (MDR) Gram-negative bacilli (GNB), which are a common cause of infection and sepsis in patients with cancer. Several investigators have reported high rates of bacteremia due to extended-spectrum β-lactamase (ESBL)producing Enterobacterales (10-13), MDR Pseudomonas aeruginosa (MDR-PA) (12,(14)(15)(16)(17), and carbapenem-resistant Enterobacterales (CRE) (18)(19)(20)(21)(22), among others, against which there are few treatment alternatives. This is of paramount importance because inadequate initial empirical antibiotic therapy can increase mortality when patients with cancer have infection due to MDR-GNB (11,(13)(14)(15)(16)(18)(19)(20)(21)(22)(23).…”