Phase II, open-label, multicenter study of combined intrathecal morphine and ziconotide: Addition of ziconotide in patients receiving intrathecal morphine for severe chronic pain

Mark S. Wallace, Peter S. Kosek, Peter Staats, Robert Fisher, David M. Schultz, Michael Leong

Research output: Contribution to journalArticle

Abstract

Objective. To assess the safety and efficacy of adding intrathecal ziconotide to intrathecal morphine in patients being treated with a stable intrathecal morphine dose. Design. Phase II, multicenter, open-label study with a 5-week titration phase and an extension phase. Setting. Outpatient clinics. Patients. Patients with suboptimal pain relief receiving stable intrathecal morphine doses (2-20mg/day). Interventions. Intrathecal morphine dosing remained constant during the titration phase. Ziconotide therapy began at 0.60μg/day and was titrated to a maximum of 7.2μg/day. During the extension phase, ziconotide and intrathecal morphine dosing were adjusted at the investigator's discretion. Outcome Measures. Safety was assessed primarily via adverse event reports. Efficacy was analyzed via percentage change on the visual analog scale of pain intensity and in weekly systemic opioid consumption. Results. Twenty-six patients were enrolled. Treatment-emergent adverse events were generally mild or moderate; the most common (≥15% of patients in either study phase) study drug-related (i.e., ziconotide/ morphine combination [or ziconotide monotherapy in the extension phase only]) events were confusion, dizziness, abnormal gait, hallucinations, and anxiety. The mean percentage improvement in visual analog scale of pain intensity scores was 14.5% (95% confidence interval: -9.4% to 38.5%) from baseline to week 5 and varied during the extension phase (range: -0.4% to 42.8%). Mean percentage change from baseline in systemic opioid consumption was -14.3% at week 5 and varied considerably during the extension phase. Conclusions. Ziconotide, combined with stable intrathecal morphine, may reduce pain and decrease systemic opioid use in patients with pain inadequately controlled by intrathecal morphine alone.

Original languageEnglish (US)
Pages (from-to)271-281
Number of pages11
JournalPain Medicine
Volume9
Issue number3
DOIs
StatePublished - Apr 2008

Fingerprint

Chronic Pain
Morphine
Multicenter Studies
Opioid Analgesics
Pain Measurement
Pain
Safety
Confusion
ziconotide
Hallucinations
Dizziness
Ambulatory Care Facilities
Gait
Anxiety
Research Personnel
Outcome Assessment (Health Care)
Confidence Intervals
Therapeutics
Pharmaceutical Preparations

Keywords

  • ChronicPain
  • CombinationTherapy
  • Intrathecal
  • Morphine
  • Ziconotide

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Phase II, open-label, multicenter study of combined intrathecal morphine and ziconotide : Addition of ziconotide in patients receiving intrathecal morphine for severe chronic pain. / Wallace, Mark S.; Kosek, Peter S.; Staats, Peter; Fisher, Robert; Schultz, David M.; Leong, Michael.

In: Pain Medicine, Vol. 9, No. 3, 04.2008, p. 271-281.

Research output: Contribution to journalArticle

Wallace, Mark S. ; Kosek, Peter S. ; Staats, Peter ; Fisher, Robert ; Schultz, David M. ; Leong, Michael. / Phase II, open-label, multicenter study of combined intrathecal morphine and ziconotide : Addition of ziconotide in patients receiving intrathecal morphine for severe chronic pain. In: Pain Medicine. 2008 ; Vol. 9, No. 3. pp. 271-281.
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abstract = "Objective. To assess the safety and efficacy of adding intrathecal ziconotide to intrathecal morphine in patients being treated with a stable intrathecal morphine dose. Design. Phase II, multicenter, open-label study with a 5-week titration phase and an extension phase. Setting. Outpatient clinics. Patients. Patients with suboptimal pain relief receiving stable intrathecal morphine doses (2-20mg/day). Interventions. Intrathecal morphine dosing remained constant during the titration phase. Ziconotide therapy began at 0.60μg/day and was titrated to a maximum of 7.2μg/day. During the extension phase, ziconotide and intrathecal morphine dosing were adjusted at the investigator's discretion. Outcome Measures. Safety was assessed primarily via adverse event reports. Efficacy was analyzed via percentage change on the visual analog scale of pain intensity and in weekly systemic opioid consumption. Results. Twenty-six patients were enrolled. Treatment-emergent adverse events were generally mild or moderate; the most common (≥15{\%} of patients in either study phase) study drug-related (i.e., ziconotide/ morphine combination [or ziconotide monotherapy in the extension phase only]) events were confusion, dizziness, abnormal gait, hallucinations, and anxiety. The mean percentage improvement in visual analog scale of pain intensity scores was 14.5{\%} (95{\%} confidence interval: -9.4{\%} to 38.5{\%}) from baseline to week 5 and varied during the extension phase (range: -0.4{\%} to 42.8{\%}). Mean percentage change from baseline in systemic opioid consumption was -14.3{\%} at week 5 and varied considerably during the extension phase. Conclusions. Ziconotide, combined with stable intrathecal morphine, may reduce pain and decrease systemic opioid use in patients with pain inadequately controlled by intrathecal morphine alone.",
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AB - Objective. To assess the safety and efficacy of adding intrathecal ziconotide to intrathecal morphine in patients being treated with a stable intrathecal morphine dose. Design. Phase II, multicenter, open-label study with a 5-week titration phase and an extension phase. Setting. Outpatient clinics. Patients. Patients with suboptimal pain relief receiving stable intrathecal morphine doses (2-20mg/day). Interventions. Intrathecal morphine dosing remained constant during the titration phase. Ziconotide therapy began at 0.60μg/day and was titrated to a maximum of 7.2μg/day. During the extension phase, ziconotide and intrathecal morphine dosing were adjusted at the investigator's discretion. Outcome Measures. Safety was assessed primarily via adverse event reports. Efficacy was analyzed via percentage change on the visual analog scale of pain intensity and in weekly systemic opioid consumption. Results. Twenty-six patients were enrolled. Treatment-emergent adverse events were generally mild or moderate; the most common (≥15% of patients in either study phase) study drug-related (i.e., ziconotide/ morphine combination [or ziconotide monotherapy in the extension phase only]) events were confusion, dizziness, abnormal gait, hallucinations, and anxiety. The mean percentage improvement in visual analog scale of pain intensity scores was 14.5% (95% confidence interval: -9.4% to 38.5%) from baseline to week 5 and varied during the extension phase (range: -0.4% to 42.8%). Mean percentage change from baseline in systemic opioid consumption was -14.3% at week 5 and varied considerably during the extension phase. Conclusions. Ziconotide, combined with stable intrathecal morphine, may reduce pain and decrease systemic opioid use in patients with pain inadequately controlled by intrathecal morphine alone.

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