Randomized controlled trial of intravenous antivenom versus placebo for latrodectism: The second redback antivenom evaluation (RAVE-II) study

Geoffrey K. Isbister, Colin B. Page, Nicholas A. Buckley, Daniel M. Fatovich, Ovidiu Pascu, Stephen P J MacDonald, Leonie A. Calver, Simon G A Brown

Research output: Contribution to journalArticleResearchpeer-review

33 Citations (Scopus)


Study objective Latrodectism is the most important spider envenomation syndrome worldwide. There remains considerable controversy over antivenom treatment. We aimed to investigate whether antivenom resulted in resolution of pain and systemic effects in patients with latrodectism who received standardized analgesia.

Methods In a multicenter randomized placebo-controlled trial of redback spider antivenom for latrodectism, 224 patients (>7 years) with a redback spider bite and severe pain, with or without systemic effects, were randomized to receive normal saline solution (placebo) or antivenom after receiving standardized analgesia. The primary outcome was a clinically significant reduction in pain 2 hours after trial medication compared with baseline. A second primary outcome for the subgroup with systemic features of envenomation was resolution of systemic features at 2 hours. Secondary outcomes were improved pain at 4 and 24 hours, resolution of systemic features at 4 hours, administration of opioid analgesics or unblinded antivenom after 2 hours, and adverse reactions.

Results Two hours after treatment, 26 of 112 patients (23%) from the placebo arm had a clinically significant improvement in pain versus 38 of 112 (34%) from the antivenom arm (difference in favor of antivenom 10.7%; 95% confidence interval -1.1% to 22.6%; P=.10). Systemic effects resolved after 2 hours in 9 of 41 patients (22%) in the placebo arm and 9 of 35 (26%) in the antivenom arm (difference 3.8%; 95% confidence interval -15% to 23%; P=.79). There was no significant difference in any secondary outcome between antivenom and placebo. Acute systemic hypersensitivity reactions occurred in 4 of 112 patients (3.6%) receiving antivenom.

Conclusion The addition of antivenom to standardized analgesia in patients with latrodectism did not significantly improve pain or systemic effects.

Original languageEnglish
Pages (from-to)620-628
Number of pages9
JournalAnnals of Emergency Medicine
Issue number6
Publication statusPublished - 1 Dec 2014
Externally publishedYes

Cite this