ClearGuard HD antimicrobial barrier caps for preventing haemodialysis catheter-related bloodstream infections

4.1 The committee noted that the literature consistently showed lower infection rates with ClearGuard compared with other options. It considered the 2 randomised controlled trials to be pivotal for decision making. While the studies had some risk of bias, the committee was reassured by the relatively large effect sizes. The way bloodstream infections were measured and reported varied across the evidence. Clinical experts said that this was a common problem in such clinical studies and also in NHS practice. The primary end point in both randomised controlled trials was positive blood cultures. The committee understood that this end point was not specifically attributable to infections arising in the central venous catheters (CVC), but nevertheless it was satisfied by the overall weight of evidence that ClearGuard HD caps are likely to reduce the risk of catheter-related bloodstream infections (CRBSI).

4.2 A clinical expert discussed the potential benefit in children who may need a central line long term, and for whom recurrent infections could limit treatment options in the future. The clinical experts said they considered the incidence rates in the adult studies to be comparable and generalisable to children. They also highlighted some evidence of a benefit for children in the Glennon et al. study, which was in high-risk children, although this evidence is lower quality because it was a retrospective analysis with limited detail and reported as an abstract only. On balance, the committee concluded that the evidence in adults could be generalised to children.

4.3 Clinical experts said that more CVCs were now being used, rather than surgical fistulas, because of the COVID‑19 pandemic. They agreed that the aim was for more people of all ages to use home dialysis. But no evidence was identified on using ClearGuard HD caps at home. The committee felt that they could benefit people having dialysis at home and was encouraged by positive feedback provided by the company from users about their usability. Clinical experts said that in their experience these patients are motivated, and so they did not see any barriers to using the caps safely and effectively at home, as long as people were trained in how to use them.

4.4 The committee discussed the ClearGuard HD caps' compatibility with central lines. It was satisfied that the only central line that they were incompatible with was one that is seldom used. The company confirmed that the caps had been shown to be compatible with other line lock solutions, as part of US Food and Drug Administration (FDA) benchmarking assessments, including heparin-saline, saline and citrate. The committee discussed 1 adverse event reported on the FDA's MAUDE (Manufacturer and User Facility Device Experience) database, of rod detachment. The committee was reassured by the company that the cap had been examined, and that the problem was not replicable and has not been reported before or since.

4.5 The rod and cap threads of ClearGuard HD caps are coated in chlorhexidine acetate, a broad-spectrum antimicrobial agent. Some people are allergic to chlorhexidine, although according to the clinical experts, this is unusual. The committee was satisfied that the device instructions for use clearly state it should not be used for people with known allergies to chlorhexidine. Clinical experts reported that in their experience allergy shows more commonly as a skin reaction, although people can have anaphylactic reactions to chlorhexidine. The committee was concerned that we do not yet know the long-term effects of exposure to chlorhexidine acetate, and if people could become sensitised to it. Because of this, the committee asked the company to proactively find out about adverse events and report them to the Medicines and Healthcare products Regulatory Agency (MHRA). The committee advised the company to provide a plan to monitor chlorhexidine sensitisation or allergies to address this gap in understanding for the future.

4.6 The clinical evidence base was all from the US and North America. The clinical experts said that the baseline rates of catheter-related bloodstream infection in the US studies were broadly comparable to UK NHS practice. A difference between the US and UK is that high-concentrate citrate is used as a catheter lock solution for adults in the UK. But it is not approved for use in this way in the US and therefore was not included in the evidence. The committee agreed that, although citrate's effect on reducing infection rates was uncertain, it was likely to be comparable to the antimicrobial line lock solution comparator in the evidence. The committee concluded that the evidence was broadly generalisable to NHS practice and was a reasonable basis for decision-making purposes.

4.7 The clinical experts said that the 'scrub the hub' disinfection practice would continue regardless of the cap used during haemodialysis. The external assessment centre (EAC) acknowledged this in its minor amendments to the company model. The committee was satisfied that this accurately showed how the caps would be used in NHS practice. It agreed that no additional changes to NHS infrastructure would be needed to use ClearGuard HD caps in the NHS.

4.8 The cost model was well constructed, and the minor changes made by the EAC were appropriate and accepted by the committee. The committee concluded that the comprehensive sensitivity and scenario analyses supported cost savings compared with all comparators.

4.9 The main cost savings were from reduced CRBSI incidence rate. The committee discussed the uncertainty around incidence levels across comparators but concluded that the evidence was strong enough and backed by clinical expert opinion, indicating that there were likely to be costs savings in practice.

4.10 The end points used in the pivotal clinical studies (positive blood cultures) introduced some uncertainty in the outcomes. However, the committee was satisfied that the EAC's extra sensitivity analysis adequately addressed the likely variation in incidence. There was some uncertainty around whether the model results were applicable to the NHS, when the evidence used to inform it did not include the comparator high-concentrate citrate, which is used in the UK but not in the US (see section 4.6). The clinical experts said infection rates with high-concentrate citrate were likely to be comparable to those with the antimicrobial line lock solution comparator used in the scenario analyses, which showed that even at low rates of baseline infection, ClearGuard HD caps were cost saving. The EAC's sensitivity analyses also showed cost savings at even lower rates of infection. The committee therefore concluded that the sensitivity analysis adequately addressed uncertainty around this comparator.

4.11 Comprehensive scenario analyses, including 'worst case' scenarios, showed ClearGuard HD caps to be cost saving compared with all comparators. Additional threshold analysis reported that they were cost neutral at infection thresholds that clinical experts advised were clinically unlikely because they were so low. The committee was satisfied that the cost modelling evidence was robust and shows ClearGuard HD caps are cost saving compared with all comparators.

4.12 The EAC revised the base-case cost savings: it added disinfection costs in the ClearGuard HD caps arm, and reduced standard caps costs because of volume discount. This resulted in cost savings per patient of: