title: Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial.
abstract: 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.
authors.affiliation: Division of Pain Medicine, Johns Hopkins University School of Medicine, Baltimore, Md 21205, USA. pstaats@jhmi.edu
authors.forename: Peter S
authors.initials: PS
authors.lastname: Staats
authors.forename: Thomas
authors.initials: T
authors.lastname: Yearwood
authors.forename: Steven G
authors.initials: SG
authors.lastname: Charapata
authors.forename: Robert W
authors.initials: RW
authors.lastname: Presley
authors.forename: Mark S
authors.initials: MS
authors.lastname: Wallace
authors.forename: Michael
authors.initials: M
authors.lastname: Byas-Smith
authors.forename: Robert
authors.initials: R
authors.lastname: Fisher
authors.forename: David A
authors.initials: DA
authors.lastname: Bryce
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Mangieri
authors.forename: Robert R
authors.initials: RR
authors.lastname: Luther
authors.forename: Martha
authors.initials: M
authors.lastname: Mayo
authors.forename: Dawn
authors.initials: D
authors.lastname: McGuire
authors.forename: David
authors.initials: D
authors.lastname: Ellis
mesh_terms: 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*
chemical_list: D000700:Analgesics; D002121:Calcium Channel Blockers; D020960:omega-Conotoxins; C078452:ziconotide