Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy. Topical capsaicin in the management of HIV-associated peripheral neuropathy. Phase III placebo-controlled trial of capsaicin cream in the management of surgical neuropathic pain in cancer patients. A randomized vehicle-controlled trial of topical capsaicin in the treatment of postherpetic neuralgia. Topical capsaicin treatment of chronic postherpetic neuralgia. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study. A double-blind comparison of topical capsaicin and oral amitriptyline in painful diabetic neuropathy. Effect of treatment with capsaicin on daily activities of patients with painful diabetic neuropathy. Capsaicin Study Group. A multicenter, randomized, double-blind, controlled study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia.
HIV-associated distal sensory polyneuropathy (HIV-DSP) is a painful condition with limited effective treatment. Capsaicin desensitizes cutaneous nociceptors resulting in reduced pain. We report a placebo-controlled study of a high-concentration capsaicin dermal patch (NGX-4010) for the treatment of painful HIV-DSP.
                This double-blind multicenter study randomized 307 patients with painful HIV-DSP to receive NGX-4010 or control, a low-concentration capsaicin patch. After application of a topical anesthetic, NGX-4010 or control was applied once for 30, 60, or 90 minutes to painful areas on the feet. The primary efficacy endpoint was percent change in Numeric Pain Rating Scale (NPRS) from baseline in mean "average pain for past 24 hours" scores from weeks 2 to 12.
                A single NGX-4010 application resulted in a mean pain reduction of 22.8% during weeks 2 to 12 as compared to a 10.7% reduction for controls (p = 0.0026). Following a transient treatment-related pain increase, pain was reduced; significant improvement was apparent by week 2 and continued throughout the controlled 12-week observation period. Mean pain reductions in the NGX-4010 30-, 60- and 90-minute groups were 27.7%, 15.9%, and 24.7% (p = 0.0007, 0.287, and 0.0046 vs control). One third of NGX-4010-treated patients reported >or=30% pain decrease from baseline as compared to 18% of controls (p = 0.0092). Self-limited, mild-to-moderate local skin reactions were commonly observed.
                A single NGX-4010 application was safe and provided at least 12 weeks of pain reduction in patients with HIV-associated distal sensory polyneuropathy. These results suggest that NGX-4010 could provide a promising new treatment for painful HIV neuropathy. Distal symmetrical peripheral neuropathy (DSPN) is a particularly distressing pain syndrome associated with human immunodeficiency virus (HIV) disease. Capsaicin has been found to be effective in relieving pain associated with other neuropathic pain syndromes, and is mentioned as a possible topical adjuvant analgesic for the relief of DSPN. This multicenter, controlled, randomized, double-masked clinical trial studied patients with HIV-associated DSPN and compared measures of pain intensity, pain relief, sensory perception, quality of life, mood, and function for patients who received topical capsaicin to the corresponding measures for patients who received the vehicle only. Twenty-six subjects were enrolled in the study. At the end of 1 week, subjects receiving capsaicin tended to report higher current pain scores than did subjects receiving the vehicle (Mann-Whitney test; P = 0.042). The dropout rate was higher for the capsaicin group (67%) than for the vehicle group (18%) (chi 2 test of association; P = 0.014). There were no other statistically significant differences between the capsaicin and vehicle groups with respect to current pain, worst pain, pain relief, sensory perception, quality of life, mood, or function at study entry or at any time during the 4-week trial. These results suggest capsaicin is ineffective in relieving pain associated with HIV-associated DSPN. A minority of cancer survivors develops long-term postsurgical neuropathic pain. Based on evidence that capsaicin, the pungent ingredient in hot chili peppers, might be useful for treating neuropathic pain, we developed the present clinical trial.
                Ninety-nine assessable patients with postsurgical neuropathic pain were entered onto this study. After stratification, patients were to receive 8 weeks of a 0.075% capsaicin cream followed by 8 weeks of an identical-appearing placebo cream, or vice versa. A capsaicin/placebo cream was to be applied to the painful site four times daily. Treatment evaluation was performed by patient-completed weekly questionnaires.
                During the first 8-week study period, the capsaicin-cream arm was associated with substantially more skin burning, skin redness, and coughing (P < .0001 for each). Nonetheless, treatment was stopped for patient refusal or toxicity just as often while patients were receiving the placebo as compared with the capsaicin. The capsaicin cream arm had substantially more pain relief (P = .01) after the first 8 weeks, with an average pain reduction of 53% versus 17%. On completion of the 16-week study period, patients were asked which treatment period was most beneficial. Of the responding patients, 60% chose the capsaicin arm, 18% chose the placebo arm, and 22% chose neither (P = .001).
                A topical capsaicin cream decreases postsurgical neuropathic pain and, despite some toxicities, is preferred by patients over a placebo by a three-to-one margin among those expressing a preference. A large double-blind, vehicle-controlled study of 143 patients with chronic postherpetic neuralgia (PHN) was performed to evaluate the degree of efficacy of topically applied capsaicin 0.075% cream. In addition, the safety and efficacy of long-term application of topical capsaicin in PHN was assessed by following patients in an open-label study for up to 2 years. In the double-blind phase, 143 patients with PHN of 6 months' duration or longer were enrolled. Since epidemiologic studies of patients who receive no treatment have shown that only 10% to 25% of those with PHN after 1 month will still have pain at 1 year, two separate efficacy analyses were performed: one with all evaluable patients (n = 131) and the other with 93 patients whose PHN lasted for longer than 12 months prior to study startup. All efficacy variables, including the physician's global evaluation of reduction in PHN pain, changes in pain severity on the categoric scale, visual analogue scale for pain severity, visual analogue scale for pain relief, and functional capacity scale, showed significant improvement at nearly all time points throughout the study for both patient groups, based on duration of PHN pain. In contrast, the group receiving vehicle cream remained essentially unchanged. Data from the long-term, open-label phase (up to 2 years, n = 77), which immediately followed the 6-week blinded phase, showed that the clinical benefit in patients treated for a short (6-week) period with topical capsaicin could be maintained or amplified in most patients (86%) during prolonged therapy. There were no serious adverse effects observed or reported throughout the trial; in fact, the only side effect associated with capsaicin treatment was the burning or stinging at local sites of application (in 9% of patients) during exposures of up to 2 years (long-term phase). On the basis of these data, we conclude that capsaicin 0.075% cream is a safe and effective treatment for the pain of postherpetic neuralgia and should be considered for initial management of patients with this condition. Uncontrolled studies have indicated that topically applied capsaicin may be a safe and effective treatment for postherpetic neuralgia. In a double-blind study 32 elderly patients with chronic postherpetic neuralgia were treated with either capsaicin cream or its vehicle for a 6-week period. Response to treatment was evaluated by visual analogue scales of pain and of pain relief, together with changes in a categoric pain scale and in a physician's global evaluation. Significantly greater relief in the capsaicin-treated group compared with vehicle was observed for all efficacy variables. After 6 weeks almost 80% of capsaicin-treated patients experienced some relief from their pain. Because capsaicin avoids problems with drug interactions and systemic toxicity, we suggest that topical capsaicin be considered for initial management of postherpetic neuralgia. The limitations of current treatments for postherpetic neuralgia (PHN) have led to the investigation of localised, non-systemic alternatives. NGX-4010, a high-concentration (8%) capsaicin dermal patch, was developed to treat patients with neuropathic pain. We report the results of a randomised, double blind, 12-week study of the efficacy and safety of one application of NGX-4010 in patients with PHN.
                In this multicentre, double-blind, parallel-group trial, 402 patients were randomly assigned to one 60-min application of NGX-4010 (640 microg/cm(2) [8% capsaicin]) or a low-concentration capsaicin control patch (3.2 microg/cm(2) [0.04% capsaicin]). Patients were aged 18-90 years, had had postherpetic neuralgia for at least 6 months, and had an average baseline numeric pain rating scale (NPRS) score of 3 to 9. The primary efficacy endpoint was percentage change in NPRS score from baseline to weeks two to eight. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00115310.
                Patients who were randomly assigned to NGX-4010 (n=206) had a significantly greater reduction in pain during weeks two to eight than did patients who had the control patch (n=196). The mean changes in NPRS score were -29.6%vs -19.9% (difference -9.7%, 95% CI -15.47 to -3.95; p=0.001). 87 (42%) patients who received NGX-4010 and 63 (32%) controls had a 30% or greater reduction in mean NPRS score (odds ratio [OR] 1.56, 95% CI 1.03 to 2.37; p=0.03). The patients who had NGX-4010 had significant improvements in pain during weeks two to 12 (mean change in NPRS score -29.9%vs -20.4%, difference -9.5, -15.39 to -3.61; p=0.002). Transient blood pressure changes associated with changes in pain level were recorded on the day of treatment, and short-lasting erythema and pain at the site of application were common, self-limited, and generally mild to moderate in the NGX-4010 group and less frequent and severe in the controls.
                One 60-min application of NGX-4010 provided rapid and sustained pain relief in patients with postherpetic neuralgia. No adverse events were associated with treatment except for local reactions at the site of application and those related to treatment-associated pain. An 8-week double-blind, multicenter, parallel study compared the safety and efficacy of topical capsaicin and oral amitriptyline in patients with painful diabetic neuropathy involving the feet. Two hundred thirty-five patients were randomized to treatment with either capsaicin cream or amitriptyline capsules. Capsaicin-treated patients received inactive capsules, and amitriptyline-treated patients applied vehicle cream. A visual analogue scale of pain intensity and measurements of interference by pain with functional activities were recorded at onset and at 2-week intervals. A visual analogue scale of pain relief and physicians' global evaluation assessed changes in pain status from baseline. Topical capsaicin and oral amitriptyline produced equal and statistically significant improvements in pain over the course of the study. By the end of week 8, 76% of patients in each group experienced less pain, with a mean reduction in intensity of more than 40%. By the end of the study, the interference with daily activities by pain had diminished significantly (P = .001) in both groups, including improvements in sleeping and walking. No systemic side effects were observed in patients treated with topical capsaicin. Most patients receiving amitriptyline experienced at least one systemic side effect, ranging from somnolence (46%) to neuromuscular (23%) and cardiovascular (9%) adverse effects. Topically applied capsaicin is an equally effective but considerably safer alternative to amitriptyline for relief of the pain of diabetic neuropathy. To establish the effects of topically applied capsaicin on daily activities in patients with painful diabetic neuropathy.
                Investigators at 12 sites enrolled 277 men and women with painful peripheral polyneuropathy and/or radiculopathy in an 8-wk double-blind vehicle-controlled study with parallel randomized treatment assignments. Participants were unresponsive or intolerant to conventional therapy and were experiencing pain that interfered with functional activities and/or sleep. Either 0.075% capsaicin cream or vehicle cream was applied to the painful areas 4 times/day. A visual analogue scale of pain intensity and baseline measurements of the pain's interference with the ability to walk, work, participate in recreational activities, use shoes and socks, sleep, and eat were recorded at onset and at 2-wk intervals. A physician's global evaluation scale assessed changes in pain status from baseline.
                Statistically significant differences are percentage of patients with improvement in favor of capsaicin versus vehicle: 69.5 vs 53.4% with clinical improvement in pain status (P = 0.012), 26.1 vs. 14.6% with improvement in walking (P = 0.029), 18.3 vs. 9.2% with improvement in working (P = 0.019), 29.5 vs. 20.3% with improvement in sleeping (P = 0.036), and 22.8 vs. 12.1% with improvement in participating in recreational activities (P = 0.037).
                The results from this study suggest that topical 0.075% capsaicin is effective for reducing pain in patients with painful diabetic neuropathy with subsequent improvement in daily activities, enhancing the quality of the patient's life. To confirm the efficacy, tolerability, and safety of NGX-4010, an 8% capsaicin dermal patch (capsaicin 640 µg/cm(2) ), in patients with postherpetic neuralgia (PHN). PHN is a chronic pain disorder that can be difficult to treat and for which current treatment options are often limited by poor tolerability.
                A total of 418 patients were randomized to receive a single 60-minute application of NGX-4010 or a 0.04% capsaicin control patch (3.2 µg/cm(2) ) in a multicenter, double-blind, confirmatory, phase 3 study.
                Patients were 18-90 years old with a diagnosis of PHN, pain for at least 6 months, and an average baseline Numeric Pain Rating Scale (NPRS) score of 3-9.
                The primary efficacy end point was the percentage change in NPRS score from baseline to weeks 2-8.
                NGX-4010 recipients had a significantly greater mean reduction from baseline in pain during weeks 2-8 compared with the control group (32.0% vs 24.4%; P=0.011). A ≥ 30% reduction in mean NPRS scores was achieved in 46% of NGX-4010 recipients compared with 34% of controls (P=0.02). Pain was significantly lower in NGX-4010 recipients than controls by week 2, and greater pain reduction was maintained throughout the remaining 12-week study period. Most treatment-emergent adverse events were application site specific (notably erythema and pain), transient, and generally mild to moderate in severity.
                In patients with PHN, a single 60-minute application of NGX-4010 produced significant reduction in pain that was maintained over a 12-week period.
                Wiley Periodicals, Inc.
High-concentration topical capsaicin used to treat postherpetic neuralgia and HIV-neuropathy generates more participants with high levels of pain relief than does control treatment using a much lower concentration of capsaicin. The additional proportion who benefit over control is not large, but for those who do obtain high levels of pain relief there are additional improvements in sleep, fatigue, depression and an improved quality of life. High-concentration topical capsaicin is therefore similar to other therapies for chronic pain. In this case, the high cost of single and repeated applications suggest that high-concentration topical capsaicin is likely to be used when other available therapies have failed, and that it should probably not be used repeatedly without substantial documented pain relief. Even when efficacy is established, there are unknown risks, especially on epidermal innervation, of repeated application of long periods.