Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies.

TitleExperience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies.
Publication TypeJournal Article
Year of Publication2013
AuthorsHarrison T, Miyahara S, Lee A, Evans S, Bastow B, Simpson D, Gilron I, Dworkin R, Daar ES, Wieclaw L, Clifford DB
Corporate AuthorsACTG A5252 Team
JournalPain Med
Volume14
Issue7
Pagination1039-47
Date Published2013 Jul
ISSN1526-4637
KeywordsAdult, Aged, Analgesics, Analgesics, Opioid, Comorbidity, Cross-Over Studies, Double-Blind Method, Drug Combinations, Duloxetine Hydrochloride, Female, HIV Infections, Humans, Male, Methadone, Middle Aged, Pain Measurement, Patient Selection, Polyneuropathies, Serotonin Uptake Inhibitors, Thiophenes, Treatment Failure, Treatment Outcome, Young Adult
Abstract

OBJECTIVE: There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared with placebo.

DESIGN: This study was a phase II, randomized, double-blind, placebo-controlled, four-period crossover multicenter study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary.

RESULTS: A total of 15 patients were enrolled from eight study sites and eight patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared with placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study dropout.

CONCLUSIONS: Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed.

DOI10.1111/pme.12084
Alternate JournalPain Med
PubMed ID23565581
PubMed Central IDPMC4207215
Grant ListAI069432 / AI / NIAID NIH HHS / United States
AI0694595 / AI / NIAID NIH HHS / United States
AI069471 / AI / NIAID NIH HHS / United States
AI069472 / AI / NIAID NIH HHS / United States
AI069501 / AI / NIAID NIH HHS / United States
AI069503 / AI / NIAID NIH HHS / United States
AI69450 / AI / NIAID NIH HHS / United States
NS32228 / NS / NINDS NIH HHS / United States
R01 NS032228 / NS / NINDS NIH HHS / United States
RR025780 / RR / NCRR NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States