Venous access devices for the delivery of long-term chemotherapy: the CAVA three-arm RCT

Abstract

Background Venous access devices are used for patients receiving long-term chemotherapy. These include centrally inserted tunnelled catheters or Hickman-type devices (Hickman), peripherally inserted central catheters (PICCs) and centrally inserted totally implantable venous access devices (PORTs). Objectives To evaluate the clinical effectiveness, safety, cost-effectiveness and acceptability of these devices for the central delivery of chemotherapy. Design An open, multicentre, randomised controlled trial to inform three comparisons: (1) peripherally inserted central catheters versus Hickman, (2) PORTs versus Hickman and (3) PORTs versus peripherally inserted central catheters. Pre-trial and post-trial qualitative research and economic evaluation were also conducted. Setting This took place in 18 UK oncology centres. Participants Adult patients (aged ≥ 18 years) receiving chemotherapy (≥ 12 weeks) for either a solid or a haematological malignancy were randomised via minimisation. Interventions Hickman, peripherally inserted central catheters and PORTs. Primary outcome A composite of infection (laboratory confirmed, suspected catheter related and exit site infection), mechanical failure, venous thrombosis, pulmonary embolism, inability to aspirate blood and other complications in the intention-to-treat population. Results Overall, 1061 participants were recruited to inform three comparisons. First, for the comparison of peripherally inserted central catheters (n = 212) with Hickman (n = 212), it could not be concluded that peripherally inserted central catheters were significantly non-inferior to Hickman in terms of complication rate (odds ratio 1.15, 95% confidence interval 0.78 to 1.71). The use of peripherally inserted central catheters compared with Hickman was associated with a substantially lower cost (–£1553) and a small decrement in quality-adjusted life-years gained (–0.009). Second, for the comparison of PORTs (n = 253) with Hickman (n = 303), PORTs were found to be statistically significantly superior to Hickman in terms of complication rate (odds ratio 0.54, 95% confidence interval 0.37 to 0.77). PORTs were found to dominate Hickman with lower costs (–£45) and greater quality-adjusted life-years gained (0.004). This was alongside a lower complications rate (difference of 14%); the incremental cost per complication averted was £1.36. Third, for the comparison of PORTs (n = 147) with peripherally inserted central catheters (n = 199), PORTs were found to be statistically significantly superior to peripherally inserted central catheters in terms of complication rate (odds ratio 0.52, 95% confidence interval 0.33 to 0.83). PORTs were associated with an incremental cost of £2706 when compared with peripherally inserted central catheters and a decrement in quality-adjusted life-years gained (–0.018) PORTs are dominated by peripherally inserted central catheters: alongside a lower complications rate (difference of 15%), the incremental cost per complication averted was £104. The qualitative work showed that attitudes towards all three devices were positive, with patients viewing their central venous access device as part of their treatment and recovery. PORTs were perceived to offer unique psychological benefits, including a greater sense of freedom and less intrusion in the context of personal relationships. The main limitation was the lack of adequate power (54%) in the non-inferiority comparison between peripherally inserted central catheters and Hickman. Conclusions In the delivery of long-term chemotherapy, peripherally inserted central catheters should be considered a cost-effective option when compared with Hickman. There were significant clinical benefits when comparing PORTs with Hickman and with peripherally inserted central catheters. The health economic benefits were less clear from the perspective of incremental cost per quality-adjusted life-years gained. However, dependent on the willingness to pay, PORTs may be considered to be cost-effective from the perspective of complications averted. Future work The deliverability of a PORTs service merits further study to understand the barriers to and methods of improving the service. Trial registration This trial is registered as ISRCTN44504648. Funding This project was funded by the National Institute for Health Research (NHIR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 47. See the NIHR Journals Library website for further project information.

Incidence, causes, and timing of peripheral intravenous catheter failure related to insertion timing in the treatment cycle in patients with hematological malignancies: A prospective descriptive study

“…Moreover, patients undergoing chemotherapy for hematologic malignancies may require longer vascular access device indwelling periods as they have persistent neutropenia, lasting 14 days or more (Zimmer & Freifeld, 2019). Due to the distinctive characteristics of hematological malignancies, some facilities use central vascular access devices (Wu et al, 2021) with longer lifespans to deliver chemotherapeutics and subsequent infusates for supportive care. However, they are known to result in more frequent BSIs (Chaftari et al, 2018;Crawford et al, 2004;Maki et al, 2006) and thrombosis (Aw et al, 2012;Blom et al, 2005;Tran et al, 2010) in these patients, compared to patients with solid tumors who use such devices.…”

Predictors of central line-associated bloodstream infections in cancer patients undergoing chemotherapy through implanted venous access ports: a cross-sectional, observational study

“…In the present study, most of the patients were diagnosed within CLABSI within 30 days, which implies that the risk factors identi ed in this paper mainly represent predictors of early complications. Despite the lack of strong evidence on the relative effectiveness and safety of these devices, the use of PICC has increased over the past decade as an alternative to the Hickman and PORT [23]. PICC implantation was conducted by the physician in charge, and data of PICC identifying predictors of CLABSI were clear, due to the data extraction strategy.…”

Scheduled removal of central venous catheters (CVC) to prevent CVC-related bloodstream infections in patients with hematological disease or autologous stem cell transplantation: a registry-based randomized simulation-study

“…Furthermore, a study on 1375 ICU patients, considered CVC use of 15 days or less as short exposure [15], and in a matched-pair analysis comparing data from an RCT with real-world data from our group [28], the median CVC time was 16 days (IQR 9-23). The median time to dCRBSI onset was 14 days (IQR [11][12][13][14][15][16][17][18][19][20][21][22].…”

“…The objective of the present study is to add further evidence against a scheduled routine CVC removal in patients with hematological diseases. Given the lack of data from randomized controlled trials (RCT) in the setting of hematological patients [ 17 ] a registry-based randomized simulation-study was used.…”