A multicenter randomized controlled clinical trial comparing central venous catheters impregnated with either 5-fluorouracil or chlorhexidine/silver sulfadiazine in preventing catheter colonization

Introduction

We conducted a national multicenter randomized clinical trial to compare the efficacy of a novel anti-infective central venous catheter (CVC) coated with 5-fluorouracil (5-FU) (Angiotech Pharmaceuticals, Vancouver, Canada) with a catheter coated with chlorhexidine and silver sulfadiazine (CH-SS) (ARROWgard Blue; Arrow International, Inc., Reading, PA, USA) in preventing catheter colonization, local site infection and catheter-related bloodstream infection (CRBSI).

Methods

Male and nonpregnant female subjects ≥ 18 years, who were initially hospitalized in an ICU and required insertion of a triple-lumen CVC, were randomized (1:1) to receive either the 5-FU or CH-SS CVCs, implanted for a maximum of 28 days. Upon removal, catheter tips were cultured using the roll-plate method. CRBSI was defined as isolation of the same species from peripheral blood and the catheter tip. Incidence rates of bacterial catheter colonization between the two treatments were compared using the Cochran–Mantel–Haenszel χ² test. To evaluate bacterial isolates for evidence of acquired 5-FU resistance, isolates cultured from catheter tips were exposed to 5-FU in vitro for a second time.

Results

Of 960 subjects who were randomized, 817 completed the study. Four hundred and nineteen were randomized to the 5-FU group and 398 to the CH-SS group. The rate of colonization of 5-FU catheters was 2.9% (n = 12) compared with 5.3% (n = 21) in the CH-SS-coated catheters (relative reduction in colonization with 5-FU coating of 46%, P = 0.055). There were no statistically significant differences (5-FU vs CH-SS) in local site infections (1.4% vs 0.9%), CRBSI (0% vs 2.8%), and the rate of adverse events related to the study devices (3.4% vs 3.5%). There was no evidence for acquired resistance to 5-FU in clinical isolates exposed to the drug for a second time.

Conclusion

The CVC coated with 5-FU is noninferior in its ability to prevent bacterial colonization of the catheter tip when compared with catheters coated with CH-SS.