Qutenza for Critical Ischaemia in End Stage Renal Failure

Peripheral vascular disease is common in end-stage renal failure (ESRF) affecting 24-77% of patients (Stack, 2005). Critical ischaemia (pain at rest caused by insufficient blood supply to a limb) is notoriously difficult to treat in this patient group. Advanced disease and extensive co-morbidities limit surgical revascularisation options of proximal vessels (Blankensteijn et al., 1996) and calciphylaxis (a process of calcification within the small vessels unique to patients with end-stage renal failure) has few effective treatments (Ng \& Peng, 2011). Often the only treatment option is symptomatic relief with strong analgesics.

Effective pain relief in patients with end-stage renal failure can be difficult to achieve. The active metabolites of many opiates are renally-excreted and side effects are more common in patients with end-stage renal failure. In particular, confusion and drowsiness limit their use. Similarly drugs commonly used for neuropathic pain, such as gabapentin, have not be investigated in clinical trials in patients with end-stage renal failure (Kurella et al., 1993).

A drug which is not renally excreted, has minimal systemic absorption and does not require dose adjustment in renal failure, is an attractive treatment option for patients with renal failure.

Qutenza (topical capsaicin 8%) is an advanced dermal application system designed for rapid delivery of capsaicin into the skin. The high concentration of capsaicin results in reversible desensitisation of TRPV-1 expressing cutaneous sensory nerve endings and reduction in nerve fibre density in the epidermis (Noto et al., 2009). The resulting pain relief is long-lasting (12 weeks after a single application) (Backonja et al., 2008); Simpson et al., 2008). Previous phase III studies have demonstrated a significant reduction in neuropathic pain in patients with post-herpetic neuralgia (Blonsky et al., 2009) and HIV neuropathy (Noto et al., 2099; Simpson et al., 2008) with a good tolerability profile and it is now licensed for use in treatment of neuropathic pain in these patient groups.

The efficacy and tolerability of Qutenza (topical capsaicin 8%) has been evaluated in over 1,600 patients within clinical trials, with a reduction in pain scores at 8 weeks from 30-32% to 20-24% compared to an active control (capsaicin 0.04%) (Simpson et al., 2008). Patients frequently developed mild irritant symptoms of erythema and itch at the site of application, but significant side effects of blistering were rare occurring in <5%.

Currently Qutenza (topical capsaicin 8%) is not licensed for the treatment of diabetics however there is evidence from a moderate number of diabetics enrolled into clinical trials that Qutenza is both safe and effective in this patient group also. Webster et al, (2011) treated a total of 91 patients with painful diabetic nephropathy and found a 31.5% reduction in mean pain scores during weeks 2-12 post treatment. There was no difference in the incidence of local side effects experienced by diabetics and non-diabetics (Backonja et al, 2011). One patient did develop an ulcer in the area of treatment however it is unclear whether this related to the treatment or not (Webster et al, 2011).

Diabetic patients will be enrolled into this trial due to the frequency of diabetic patients with renal failure and the contributing role of diabetes in small vessel disease leading to critical ischaemia. The distinction between painful diabetic neuropathy and digital critical ischaemia can be difficult to make clinically and it may be that a small proportion of patients recruited for this study also have an element of diabetic neuropathy in addition to their critical ischaemia. In view of the concern with ulceration of the feet in diabetics treated with Qutenza, patients with diabetic neuropathy causing a loss of sensation will be excluded from having their feet treated.

Pain from critical ischaemia is multi-modal and notoriously difficult to treat particularly in patients with established renal failure in whom other analgesic agents are poorly tolerated. A drug such as Qutenza (topical capsaicin 8%) which is not renally excreted, has minimal systemic absorption and does not require dose adjustment in renal failure, is an attractive treatment option for patients with renal failure.

This is a single centre, prospective observational trial evaluating efficacy and tolerability of Qutenza (topical capsaicin 8%) for the treatment of digital critical ischaemia in patients with end stage renal failure.

Primary Objective:

• To evaluate the safety and efficacy of Qutenza (topical capsaicin 8%) in relieving chronic neuropathic pain from digital critical ischaemia in patients with end stage renal failure

Secondary objective:

• To evaluate Quality of Life (QoL) measures in patients with end stage renal failure who have chronic neuropathic pain from critical ischaemia treated with Qutenza (topical capsaicin 8%)