3 Clinical evidence

3 Clinical evidence

Summary of clinical evidence

3.1 The key clinical outcomes for the 3M Tegaderm CHG IV securement dressing (Tegaderm CHG) presented in the decision problem were:

  • catheter‑related bloodstream infections (CRBSI)

  • skin and catheter colonisation

  • length of stay in critical care or high dependency unit

  • mortality caused by catheter‑related infections

  • dermatitis

  • local site infection

  • quality of life

  • device‑related adverse events.

3.2 The company identified 5 studies that met their inclusion criteria. There were 3 studies (Maryniak et al. 2009; Olson et al. 2008; Rupp et al. 2008) that reported nursing satisfaction scores on various aspects of dressing design and performance; these were excluded from the clinical evidence review (see section 3.11). An unpublished study by Scoppettuolo et al. (2012) was also excluded because the results from intensive care unit and non‑intensive care unit patients were not reported separately. The company presented the remaining study by Timsit et al. (2012).

3.3 The External Assessment Centre agreed with including Timsit et al. (2012) and excluding the 4 remaining studies identified.

3.4 The External Assessment Centre carried out a further literature search to identify all prospective comparative studies including at least 2 of the 3 dressing types in the scope: Tegaderm CHG, a semipermeable transparent (standard) dressing and a chlorhexidine gluconate (CHG)‑impregnated dressing. This search returned 1755 records of which 4 were considered relevant. Of the 4 studies identified, 2 involved Tegaderm. One of the 2 studies involving Tegaderm was presented by the company (Timsit et al. 2012); the other was identified by the company as an ongoing study (Karpanen et al. 2014) with interim results published after the company's submission of evidence. The External Assessment Centre considered the Timsit et al. (2012) study to be relevant to the decision problem despite the fact that both the intervention and control groups were not swabbed with 2% CHG in alcohol as specified in the decision problem. The other 2 studies (Timsit et al. 2009; Roberts et al. 1998) compared a CHG‑impregnated sponge dressing (Biopatch, Johnson and Johnson) against standard dressings, and were included by the External Assessment Centre to provide an indirect comparison between Tegaderm CHG and a CHG‑impregnated dressing.

3.5 Timsit et al. (2012) reported a large multicentre randomised controlled trial, based in 12 intensive care units in France, involving 1879 patients and 4163 intravascular catheters (2201 arterial and 1962 central venous catheters). Patients needing intravascular access were randomised to 1 of 3 groups: Tegaderm CHG (938 patients), standard dressing (Tegaderm transparent film dressing; 476 patients) or highly‑adhesive dressing (Tegaderm HP transparent film dressing; 465 patients). Assessors were blinded to dressing type. Patients had their skin prepared with povidone‑iodine in alcohol or 0.5% chlorhexidine in alcohol. Dressings were replaced after 24 hours and then every 3–7 days depending on the centre, or as needed if there was leaking or soiling. The study follow‑up period was 48 hours after discharge from the intensive care unit.

3.6 Outcomes were reported on an intention‑to‑treat basis. These were reported for each group, and comparative statistical analyses were done between the Tegaderm CHG group and the 2 non‑CHG‑dressing groups combined (the standard and highly‑adhesive dressing groups), and between the standard dressing group and the highly‑adhesive dressing group. Results showed that CRBSI rates were significantly lower in the Tegaderm CHG group, at 0.5 per 1000 catheter days compared with 1.3 for the highly‑adhesive dressing and standard dressing groups combined (hazard ratio [HR] for CHG compared with non‑CHG dressings 0.402; 95% confidence interval [CI] 0.186 to 0.868, p=0.02). Catheter and skin colonisation were significantly lower in the Tegaderm CHG group at 4.3 per 1000 catheter days compared with 9.6 for the standard dressing group, 12.5 for the highly‑adhesive dressing group, and 10.9 for the 2 non‑CHG dressing groups combined (HR for CHG compared with non‑CHG dressings 0.412; 95% CI 0.306 to 0.556, p<0.0001). Major catheter‑related infections (defined as catheter‑related sepsis with or without CRBSI), were also significantly lower in the Tegaderm CHG group, at 0.7 per 1000 catheter days compared with 2.3 for the standard dressing group and 1.9 for the highly‑adhesive dressing group (HR for CHG compared with non‑CHG dressings 0.328; 95% CI 0.174 to 0.619, p=0.0006). Patients with a Tegaderm CHG dressing had a significantly higher rate of severe contact dermatitis needing removal of the dressing; 1.1% compared with 0.1% for the standard dressing and 0.5% for the highly‑adhesive dressing, p<0.0001. Also, abnormal International Contact Dermatitis Research Group (ICDRG) scores, measured at each dressing change and at catheter removal, were significantly higher for Tegaderm CHG at 2.3%, compared with 1% for the non‑CHG dressings (0.7% for the standard dressing and 1.4% for the highly‑adhesive dressing, p<0.0001). No systemic adverse events related to any of the dressings were reported. The authors concluded that Tegaderm CHG was associated with a lower rate of major catheter‑related infections than either of the non‑CHG dressings.

3.7 Karpanen et al. (2014) reported interim results, in the form of a poster presentation, of a non‑randomised prospective comparative observational study of 273 intensive care unit patients at University Hospitals Birmingham NHS Foundation Trust. Patients had Tegaderm CHG or a standard dressing (Tegaderm IV dressing). Patients in both groups had standard catheter care, including skin preparation with 2% CHG in 70% alcohol. Based on interim results in the 273 patients, there were 10 instances (7.4%) of colonisation of the intradermal section of the central venous catheter in the Tegaderm CHG group compared with 22 (14.6%) in the standard dressing group (p=0.037). There were 10 instances (7.4%) of tip colonisation of the central venous catheter reported in the Tegaderm CHG group compared with 20 instances (16.1%) in the standard dressing group (p=0.08). Adverse events were not reported. The authors concluded that adopting Tegaderm CHG reduced bacterial numbers on the skin and reduced the bacterial load at the central venous catheter insertion site compared with the standard dressing.

Studies on the comparator technologies

3.8 Timsit et al. (2009) reported on a multicentre, 2×2 factorial randomised controlled trial involving 1636 patients in 7 intensive care units in France. The study had 2 aims: to assess the superiority of a CHG‑impregnated sponge compared with a standard dressing on rates of major catheter‑related infection; and to determine the effect on outcomes of a 3- or 7‑day dressing change. Patients were randomised to 1 of 4 groups by both dressing type (CHG‑impregnated sponge [Biopatch] plus a standard dressing [Tegaderm] or a standard dressing alone) and frequency of dressing change (every 3 or 7 days). In all patients an antiseptic solution of 5% povidone‑iodine in 70% ethanol was applied and all dressings were changed 24 hours after catheter insertion and then every 3 or 7 days. The follow‑up period was 48 hours after discharge from the intensive care unit, and all outcomes were based on intention‑to‑treat analyses.

3.9 CRBSI rates were significantly lower in the CHG‑impregnated sponge group at 0.4 per 1000 catheter days compared with 1.3 for the standard dressing group (HR 0.24; 95% CI 0.09 to 0.65, p=0.005). Catheter and skin colonisation rates were significantly lower in the CHG‑impregnated sponge group, 0.6 per 1000 catheter days compared with 1.4 for the standard dressing group (HR 0.36; 95% CI 0.28 to 0.46, p<0.001). Major catheter‑related infection rates were significantly lower in the CHG‑impregnated sponge group, 0.6 per 1000 catheter days compared with 1.4 for the standard dressing group (HR 0.39; 95% CI 0.16 to 0.93, p=0.03). There was no statistically significant difference in these outcomes between the 3- or 7‑day dressing change groups.

3.10 The rate of severe contact dermatitis, needing removal of the dressing, was 0.53% for the CHG‑impregnated sponge group and 0% for the standard dressing group (no statistical analyses reported). Abnormal ICDRG scores, measured at each dressing change and at catheter removal, were significantly higher for the CHG‑impregnated sponge group at 1.49% compared with 1.02% for the standard dressing group, p=0.02. No systemic adverse events related to the dressings were reported. The authors concluded that the CHG‑impregnated sponge dressing was associated with a reduction in the risk of infection, even with low background infection rates, compared with the standard dressing.

3.11 Roberts et al. (1998) carried out a single‑centre randomised controlled trial involving 32 patients with 40 catheters in an Australian intensive care unit. Patients were randomised to have a CHG‑impregnated sponge (Biopatch) plus a standard dressing or a standard dressing alone (Opsite IV 3000, Smith and Nephew). Skin was prepared with 0.5% CHG in alcohol and dressings were changed every 3 days. There was 1 CRBSI in the CHG-impregnated sponge group, and none in the standard dressing group (p value not reported). There were 2 instances of catheter colonisation on the central venous catheter tip, and 4 at the exit site in the CHG‑impregnated sponge group compared with 1 case and 3 cases respectively for the standard dressing group; neither difference was statistically significant. Adverse events were not reported. The authors stated that the data were insufficient to draw conclusions from this study.

3.12 The External Assessment Centre critically appraised the methodology of each study. It judged that the studies by Timsit et al. (2009 and 2012) were the most relevant and best conducted. The study by Roberts et al. (1998) was underpowered to determine the statistical significance of outcomes; provided few details on the methodology used; included no details on how randomisation was achieved; and only provided information on age and gender of the study population at baseline. The poster presentation by Karpanen et al. (2014) contained insufficient detail for the External Assessment Centre to fully appraise its methodology and accurately judge its relevance to the decision problem.

3.13 The External Assessment Centre considered the company's submission to be consistent with the scope. However, it noted that the company's submission did not compare Tegaderm CHG with other CHG‑impregnated dressings because no direct comparative evidence was found in the literature review. The Timsit et al. (2012) study included by the company used internationally‑recognised definitions for catheter colonisation and CRBSI. Mortality caused by catheter‑related infections, local site infection, and quality of life were not addressed in the company's submission. However, given the evidence for a link between CRBSI and mortality, the External Assessment Centre considered it plausible that if Tegaderm CHG reduced CRBSI, it would have a positive effect on CRBSI‑related mortality in practice. The External Assessment Centre noted that the CRBSI rate of 1.3 per 1000 catheter days reported in Timsit et al. (2012) was similar to that reported for the NHS in England in the Matching Michigan study of 1.48 per 1000 catheter days, making its results generalisable to the NHS. However, it also noted that the mortality of 31% for the intensive care units in France in the Timsit studies was substantially higher than the 9.1% mortality reported for adult critical care units in the NHS. This suggests that whereas their demographics were similar, the intensive care units in France probably had more severely ill patients than the UK intensive care units. The skin preparation protocols followed by the intensive care units in France differed from those recommended for the NHS, which were specified in the decision problem.

Adverse events

3.14 The company searched the Medicines and Healthcare Products Regulatory Agency (MHRA) and Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) systems to identify surveillance reports relating to Tegaderm CHG, between 7 January 2000 and 29 July 2013. This revealed 1 result from the MHRA and 109 results from MAUDE. The company also searched its post‑marketing surveillance data for reported skin reactions. This identified a marked reduction in reports, both in numbers and relative to increasing sales, after a modification to the dressing design in 2011 to incorporate a breathable film.

3.15 The External Assessment Centre found that the company's search of the MAUDE and MHRA systems accurately reported, in detail, the adverse events for Tegaderm CHG. Overall, it considered the company's search for adverse events to be robust.

3.16 The External Assessment Centre extended the company's search to 28 November 2014 and identified a further 17 results. These results generally described local skin reactions within 48 hours of dressing application, and many were self‑limiting. There were 2 deaths reported in MAUDE, but these were not directly linked to Tegaderm CHG.

3.17 The company also did a search of the MHRA and MAUDE systems to identify post‑marketing surveillance reports for the Biopatch (CHG‑impregnated sponge) and Opsite IV 3000 (standard) dressings, but it did not report the search terms and dates used. The External Assessment Centre did its own searches of these systems between 1 January 2012 and 30 November 2014. These searches identified 73 records for Biopatch, which were similar in nature to the 29 records for Tegaderm CHG over the same period. However, the External Assessment Centre emphasised that these figures allow no comparison of event rates because no data were available on the numbers of dressings used over this period. One record reported a death; however this was not directly linked to Biopatch. Only 1 minor, self‑correcting adverse reaction was found for the Opsite IV 3000 dressing over this period.

Committee considerations

3.18 The Committee considered that the evidence showed that Tegaderm CHG was effective in reducing CRBSI compared with standard semipermeable transparent dressings. It considered that the Tegaderm CHG and CHG‑impregnated sponge dressings were clinically equivalent in terms of reducing CRBSI. However, it noted that Tegaderm CHG offers the additional benefit of being able to see the catheter insertion site. The Committee was advised by clinical experts that being able to see the catheter insertion site allows the care bundle checks that are needed to minimise infection rates. It was also advised that nurses find Tegaderm CHG easier to apply than CHG‑impregnated sponge dressings.

3.19 The Committee noted that the study evidence was largely from intensive care units in France that followed different skin preparation guidelines and that may have had more severely ill patients than those generally found in the UK. The Committee considered that this evidence was nevertheless generalisable to the UK, based on advice from experts and the External Assessment Centre and on the knowledge of its members.

3.20 The Committee heard from clinical experts that different definitions and measurement methods are used to diagnose CRBSI, making comparison of infection rates difficult. It was advised that a diagnosis of CRBSI should involve tests to confirm that the catheter was the source of the bloodstream infection (typically culture of the catheter tip). It discussed using less rigorous definitions; specifically central line associated bloodstream infection (CLABSI), which is used in hospitals where cultures of the tip, or peripheral blood, are not systematically done. The Committee was advised that using CLABSI risked overestimating the rate of CRBSI and therefore overestimating any potential cost savings from using Tegaderm CHG.

3.21 The Committee was advised by clinical experts that introducing care bundles into intensive care units had significantly reduced rates of CRBSI, but that it is not possible to identify which specific components of a care bundle have led to the reductions in infection rates. It was advised that Tegaderm CHG could be used with existing care bundles as an additional method for minimising rates of CRBSI, but it would not replace the need to use care bundles. The Committee noted that in some hospitals existing infection control procedures may have reduced baseline CRBSI rates to such low levels that they may not be able to realise the benefits of introducing Tegaderm CHG (see section 5.19).

  • National Institute for Health and Care Excellence (NICE)