Crotalidae polyvalent immune antivenom (CroFab) improved limb disability in patients bitten by copperhead snakes.
Why does this matter?
RCTs in toxicology are very rare. Early studies of CroFab were performed in patients with rattlesnake bites, not copperhead snakebites. In fact, there was no RCT data prior to this to support CroFab use for any type of snakebite. An earlier retrospective observational study in 2004 found CroFab halted progression of tissue destruction in the majority of patients with copperhead bites, but time to return to work and long-term limb disability were not measured. In fact, this 2004 paper called for a more rigorous trial like the one we are covering today.
Copperhead - like a penny that bites you
This was a small RCT with patients who had mild to moderate copperhead envenomation, with 45 in the CroFab group (roughly 6 vials) and 29 placebo patients. All had limb disability measured at 14 days post-bite. The limb disability score was 1 point better in the CroFab group, and they needed less pain medicine. Most bites were considered mild severity. This was a small improvement and of questionable clinical significance. There was no long-term improvement in functional outcome. And it must be acknowledged that 10 of the 17 authors received funding or support from BTG International, and the study was supported by BTG International, makers of CroFab. Regardless, this was a major accomplishment given 18 centers across the US and the sporadic nature of these bites. It gives us the highest quality evidence for antivenom in copperhead (or other crotaline) snakebites that exists, as far as I am aware. Plus they established the primary outcome and made no changes on clinicaltrials.gov. Keep in mind, severe bites with hypotension or coagulopathy were excluded. These would certainly warrant treatment with antivenom and were not addressed by this article.
So should you give it in mild bites? It is worth having an open discussion of the expected benefits with patients who have mild bites, given the very high cost of this antivenom: $2000-2900 per vial plus additional hospital charges. If it were me, and I was self-pay, I would appreciate a frank discussion of the staggering cost for the medicine vs. the very small short-term and absent long-term improvement in outcome. You'll have to make the call on a case by case basis based on severity of the bite, poison center recommendations, and dialogue with the patient.
The Efficacy of Crotalidae Polyvalent Immune Fab (Ovine) Antivenom Versus Placebo Plus Optional Rescue Therapy on Recovery From Copperhead Snake Envenomation: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial. Ann Emerg Med. 2017 Aug;70(2):233-244.e3. doi: 10.1016/j.annemergmed.2017.04.034. Epub 2017 Jun 13.
Peer reviewed by Thomas Davis, MD.