Context Ziconotide (formerly SNX-111) selectively blocks N-type voltage-sensitive
calcium channels and may be effective in patients with pain that is refractory
to opioid therapy or those with intolerable opioid-related adverse effects.
Objective To assess the safety and efficacy of intrathecal ziconotide in patients
with pain that is refractory to conventional treatment.
Design, Setting, and Patients Double-blind, placebo-controlled, randomized trial conducted from March
12, 1996, to July 11, 1998, at 32 study centers in the United States, Australia,
and the Netherlands. Patients were 111 individuals ages 24 to 85 years with
cancer or AIDS and a mean Visual Analog Scale of Pain Intensity (VASPI) score
of 50 mm or greater. Patients were randomly assigned in a 2:1 ratio to receive
ziconotide or placebo treatment.
Interventions Intrathecal ziconotide was titrated over 5 to 6 days, followed by a
5-day maintenance phase for responders and crossover of nonresponders to the
opposite treatment group.
Main Outcome Measure Mean percentage change in VASPI score from baseline to the end of the
initial titration period.
Results Of the evaluable population, 67 (98.5%) of 68 patients receiving ziconotide
and 38 (95%) of 40 patients receiving placebo were taking opioids at baseline
(median morphine equivalent dosage of 300 mg/d for the ziconotide group and
600 mg/d for the placebo group; P = .63, based on
mean values), and 36 had used intrathecal morphine. Mean (SD) VASPI scores
were 73.6 (1.8) mm in the ziconotide group and 77.9 (2.3) mm in the placebo
group (P = .18). Mean VASPI scores improved 53.1%
(95% confidence interval [CI], 44.0%-62.2%) in the ziconotide group and 18.1%
(95% CI, 4.8%-31.4%) in the placebo group (P<.001),
with no loss of efficacy of ziconotide in the maintenance phase. Pain relief
was moderate to complete in 52.9% of patients in the ziconotide group compared
with 17.5% in the placebo group (P<.001). Five
patients receiving ziconotide achieved complete pain relief, and 50.0% of
patients receiving ziconotide responded to therapy compared with 17.5% of
those receiving placebo (P = .001).
Conclusion Intrathecal ziconotide provided clinically and statistically significant
analgesia in patients with pain from cancer or AIDS.