Qutenza for Critical Ischaemia in End Stage Renal Failure
Qutenza for Critical Ischaemia in End Stage Renal Failure
Critical ischaemia is pain at rest as the result of poor blood flow and lack of oxygen being
 delivered to the tissues. It normally affects the hands and feet and can be very
 debilitating. It is particularly common and difficult to treat in patients with end stage
 renal failure

 Patients with renal failure are often high risk of any operative intervention which might
 help the pain. Often the only treatment options are painkillers. Unfortunately however, the
 commonly used painkillers, for example morphine, are known to cause worse side effects in
 patients with renal failure (drowsiness, confusion etc.

 Qutenza (topical capsaicin 8%) is a new treatment made from chilli peppers which is applied
 to the skin as a patch and works directly at the nerve endings in the skin to prevent pain.
 It therefore should not have the systemic side effects of other drugs. It has been
 demonstrated to be beneficial in other painful conditions for example post-shingles pain and
 nerve pain from HIV. It has never been used for critical ischaemia before.

 We propose to investigate the efficacy of Qutenza in treating patients with end stage renal
 failure and painful ischaemia. We will recruit 20 patients with painful ischaemia and treat
 them with Qutenza. We will follow them up for 12 weeks and monitor the change in their pain
 scores.
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%)
Inclusion Criteria:

 -  All adult patients > 18 years old with end stage renal disease on dialysis and
 critical ischaemia defined as rest pain most days for >3 months

 Exclusion Criteria:

 -  Pre-dialysis

 -  Hypersensitivity to Qutenza, Emla or any of the excipients

 -  Broken skin or active ulceration at the site of application

 -  Severe uncontrolled hypertension (systolic BP >200)

 -  Proven cardiac event during the preceding 3 months

 -  Women who are pregnant or breast feeding

 -  Diabetic neuropathy resulting in a loss of sensation

 -  Lack of capacity or inability to provide informed consent

 -  Declines participation in the study