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A randomized trial evaluating Prosaptide for HIV-associated sensory neuropathies: use of an electronic diary to record neuropathic pain.

Evans SR, Simpson DM, Kitch DW, King A, Clifford DB, Cohen BA, McArthur JC, Neurologic AIDS Research ConsortiumAIDS Clinical Trials Gro - PLoS ONE (2007)

Bottom Line: We examined PRO against placebo (PBO) for treatment of painful HIV-SN and performed a post-hoc evaluation of an electronic diary (ED) to record HIV-associated neuropathic pain.There were no between-group differences in the frequency of adverse events or laboratory toxicities.The 6-week mean (sd) Gracely pain scale changes were -0.12 (0.23), -0.24 (0.35), -0.15 (0.32), -0.18 (0.34), and -0.18 (0.32) for the 2, 4, 8, 16 mg, and PBO arms respectively.

View Article: PubMed Central - PubMed

Affiliation: Harvard School of Public Health, Boston, Massachusetts, United States of America. evans@sdac.harvard.edu

ABSTRACT

Objectives: To examine the efficacy and safety of Prosaptide (PRO) for the treatment of painful HIV-associated sensory neuropathies (HIV-SN).

Design: A randomized, double-blind, placebo-controlled, multicenter study in participants with sensory neuropathy. Pain modulating therapy was discontinued prior to baseline. Participants were stratified by sural sensory nerve action potential (SNAP) amplitude. Participants were trained to use an electronic diary (ED) to record pain.

Setting: Peripheral neuropathies are common complications of HIV infection. The pathogenesis is unknown and currently treatments are restricted to symptomatic measures. We examined PRO against placebo (PBO) for treatment of painful HIV-SN and performed a post-hoc evaluation of an electronic diary (ED) to record HIV-associated neuropathic pain.

Participants: Eligible participants included adults with neurologist-confirmed painful HIV-SN.

Interventions: 2, 4, 8, or 16 mg/d PRO or PBO administered via subcutaneous (SC) injection for six weeks. Neurotoxic antiretroviral drug usage was held constant.

Outcome measures: Changes from baseline in the weekly average of evaluable daily random prompts measuring pain using the Gracely pain scale and adverse events.

Results: 237 participants were randomized. The study was stopped after a planned futility analysis. There were no between-group differences in the frequency of adverse events or laboratory toxicities. The 6-week mean (sd) Gracely pain scale changes were -0.12 (0.23), -0.24 (0.35), -0.15 (0.32), -0.18 (0.34), and -0.18 (0.32) for the 2, 4, 8, 16 mg, and PBO arms respectively. A similar variability of pain changes recorded using the ED were noted compared to previous trials that used paper collection methods.

Conclusions: 6-week treatment with PRO was safe but not effective at reducing HIV-associated neuropathic pain. Use of an ED to record neuropathic pain is novel in HIV-SN, resulted in reasonable compliance in recording pain data, but did not decrease the variability of pain scores compared to historical paper collection methods.

Trial registration: Current Controlled Trials NCT00286377.

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Related in: MedlinePlus

Difference of Mean Gracely Pain Score Changes (Using LOCF) between each Dosing Group and Placebo across Weeks.
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pone-0000551-g002: Difference of Mean Gracely Pain Score Changes (Using LOCF) between each Dosing Group and Placebo across Weeks.

Mentions: Pain decreased in all arms. The 6-week mean (sd) Gracely pain scale changes (using LOCF) were −0.12 (0.23), −0.24 (0.35), −0.15 (0.32), −0.18 (0.34), and −0.18 (0.32) for the 2, 4, 8, 16 mg, and PBO arms respectively. No statistically significant differences between any PRO arm and PBO were noted (Figure 2). LOCF imputation was required on 33/229 (14.4%) observations. Sensitivity analyses using other methods for missing data yielded similar results, as did treatment comparisons of pain changes assessed using the VAS. There was insufficient evidence to conclude that the “treatment success” rates for the 2 mg (19%), 4 mg (28 %), 8 mg (22 %), and 16 mg (28%), were different from PBO (22%). The median number of times that rescue medication was used per day during the study was comparable: placebo (0.26), 2 mg (0.44), 4 mg (0.45), 8 mg (0.48), and 16 mg (0.38).


A randomized trial evaluating Prosaptide for HIV-associated sensory neuropathies: use of an electronic diary to record neuropathic pain.

Evans SR, Simpson DM, Kitch DW, King A, Clifford DB, Cohen BA, McArthur JC, Neurologic AIDS Research ConsortiumAIDS Clinical Trials Gro - PLoS ONE (2007)

Difference of Mean Gracely Pain Score Changes (Using LOCF) between each Dosing Group and Placebo across Weeks.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1919427&req=5

pone-0000551-g002: Difference of Mean Gracely Pain Score Changes (Using LOCF) between each Dosing Group and Placebo across Weeks.
Mentions: Pain decreased in all arms. The 6-week mean (sd) Gracely pain scale changes (using LOCF) were −0.12 (0.23), −0.24 (0.35), −0.15 (0.32), −0.18 (0.34), and −0.18 (0.32) for the 2, 4, 8, 16 mg, and PBO arms respectively. No statistically significant differences between any PRO arm and PBO were noted (Figure 2). LOCF imputation was required on 33/229 (14.4%) observations. Sensitivity analyses using other methods for missing data yielded similar results, as did treatment comparisons of pain changes assessed using the VAS. There was insufficient evidence to conclude that the “treatment success” rates for the 2 mg (19%), 4 mg (28 %), 8 mg (22 %), and 16 mg (28%), were different from PBO (22%). The median number of times that rescue medication was used per day during the study was comparable: placebo (0.26), 2 mg (0.44), 4 mg (0.45), 8 mg (0.48), and 16 mg (0.38).

Bottom Line: We examined PRO against placebo (PBO) for treatment of painful HIV-SN and performed a post-hoc evaluation of an electronic diary (ED) to record HIV-associated neuropathic pain.There were no between-group differences in the frequency of adverse events or laboratory toxicities.The 6-week mean (sd) Gracely pain scale changes were -0.12 (0.23), -0.24 (0.35), -0.15 (0.32), -0.18 (0.34), and -0.18 (0.32) for the 2, 4, 8, 16 mg, and PBO arms respectively.

View Article: PubMed Central - PubMed

Affiliation: Harvard School of Public Health, Boston, Massachusetts, United States of America. evans@sdac.harvard.edu

ABSTRACT

Objectives: To examine the efficacy and safety of Prosaptide (PRO) for the treatment of painful HIV-associated sensory neuropathies (HIV-SN).

Design: A randomized, double-blind, placebo-controlled, multicenter study in participants with sensory neuropathy. Pain modulating therapy was discontinued prior to baseline. Participants were stratified by sural sensory nerve action potential (SNAP) amplitude. Participants were trained to use an electronic diary (ED) to record pain.

Setting: Peripheral neuropathies are common complications of HIV infection. The pathogenesis is unknown and currently treatments are restricted to symptomatic measures. We examined PRO against placebo (PBO) for treatment of painful HIV-SN and performed a post-hoc evaluation of an electronic diary (ED) to record HIV-associated neuropathic pain.

Participants: Eligible participants included adults with neurologist-confirmed painful HIV-SN.

Interventions: 2, 4, 8, or 16 mg/d PRO or PBO administered via subcutaneous (SC) injection for six weeks. Neurotoxic antiretroviral drug usage was held constant.

Outcome measures: Changes from baseline in the weekly average of evaluable daily random prompts measuring pain using the Gracely pain scale and adverse events.

Results: 237 participants were randomized. The study was stopped after a planned futility analysis. There were no between-group differences in the frequency of adverse events or laboratory toxicities. The 6-week mean (sd) Gracely pain scale changes were -0.12 (0.23), -0.24 (0.35), -0.15 (0.32), -0.18 (0.34), and -0.18 (0.32) for the 2, 4, 8, 16 mg, and PBO arms respectively. A similar variability of pain changes recorded using the ED were noted compared to previous trials that used paper collection methods.

Conclusions: 6-week treatment with PRO was safe but not effective at reducing HIV-associated neuropathic pain. Use of an ED to record neuropathic pain is novel in HIV-SN, resulted in reasonable compliance in recording pain data, but did not decrease the variability of pain scores compared to historical paper collection methods.

Trial registration: Current Controlled Trials NCT00286377.

Show MeSH
Related in: MedlinePlus