Investigation of topical intranasal cocaine for sinonasal procedures: a randomized, phase III clinical trial

Abstract

Background: The objective of this trial was to demonstrate the clinical efficacy and safety of topical cocaine as part of the effort to gain regulatory approval from the United States Food and Drug Administration. Methods: This phase III, randomized, prospective, double-blind, multicenter, single-dose, placebo-and dosecontrolled, parallel-group study aimed to evaluate the safety and efficacy of topical intranasal cocaine (RX0041-002). A total of 925 subjects were screened and a total of 648 subjects were randomized: 95 to placebo; 275 to 4% RX0041-002; and 278 to 8% RX0041-002. Efficacy was assessed with subjective pain intensity scores using the visual numeric rating scale and objectively using the von Frey filament test. Adverse events (AEs), vital signs, Holter monitoring, nasal irritation on visual examination, and smell assessment were recorded. The placebo and experimental groups were compared using a two-tailed Fisher's exact test. Results: Topical 4% and 8% cocaine achieved significant subject analgesia, the primary efficacy endpoint. Both doses were safe and well-tolerated, with a safety profile similar to placebo. In the 4% and 8% groups, headache (1.5% and 2.5%, respectively), epistaxis (0.7% and 1.1%), and anxiety (0.7% and 0%) were the only AEs reported by >1 subject. No cardiovascular AEs, serious AEs, or deaths occurred. A higher percentage of subjects in the 4% and 8% groups compared with the placebo group had a modest increase in either systolic or diastolic blood pressure. Conclusion: Topical 4% and 8% cocaine is an effective anesthetic that can be safely administered for nasal procedures.

Comment on “Investigation of topical intranasal cocaine for sinonasal procedures: a randomized, phase III clinical trial”

“…As cited by McGrath et al., 1 a direct comparison of oxymetazoline and lidocaine shows it to be as effective as cocaine with a longer duration of analgesic effects 3 . Results for tetracaine and oxymetazoline are similar in comparison to cocaine 4 .…”

“…We reviewed the article by McGrath et al 1 . with great interest, but would like to raise some concerns, many of which were previously articulated when Long et al 2 .…”

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“…Recently, a study found that topical 4% and 8% cocaine is an effective anesthetic that can be safely administered for nasal procedures based on a randomized phase III clinical trial. This study aims to favor approval by the United States Food and Drug Administration (FDA) because many otolaryngologists frequently utilize topical cocaine in their practice [4]. For example, in a large survey of active members of the American Academy of Otolaryngology-Head and Neck Surgery, which was published in 2004, fifty percent of respondents reported using cocaine as a topical agent during endoscopic sinus surgery over the preceding calendar year [5].…”

Reply to: Comment on “Investigation of topical intranasal cocaine for sinonasal procedures: a randomized, phase III clinical trial”

“…However, these changes were transient and inconsequential. There were no major adverse events such as arrhythmia nor cardiac arrest 5 …”

“…We also reiterated the notion that the use of topical cocaine in conjunction with other vasoconstrictive agents (ie, epinephrine) can produce adverse events. Thus is should be avoided in patients with significant cardiac histories 5 . We feel that Francis et al., 1 who are at a large academic institution with a well‐known otolaryngology department, should have consulted with these individuals regarding their usage of cocaine.…”