Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial.
BACKGROUND
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.


METHODS
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.


METHODS
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.


METHODS
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).


CONCLUSIONS
Intrathecal ziconotide provided clinically and statistically significant analgesia in patients with pain from cancer or AIDS.
Staats
Peter S
PS
Division of Pain Medicine, Johns Hopkins University School of Medicine, Baltimore, Md 21205, USA. pstaats@jhmi.edu
Yearwood
Thomas
T
Charapata
Steven G
SG
Presley
Robert W
RW
Wallace
Mark S
MS
Byas-Smith
Michael
M
Fisher
Robert
R
Bryce
David A
DA
Mangieri
Eugene A
EA
Luther
Robert R
RR
Mayo
Martha
M
McGuire
Dawn
D
Ellis
David
D
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D010148:Intractable Pain / Q000188:drug therapy / Q000209:etiology; D020960:omega-Conotoxins / Q000008:administration & dosage / Q000627:therapeutic use*
D000700:Analgesics; D002121:Calcium Channel Blockers; D020960:omega-Conotoxins; C078452:ziconotide