Richard C Dart1, Sean P Bush2, Kennon Heard3, Thomas C Arnold4, Mark Sutter5, Danielle Campagne6, Christopher P Holstege7, Steven A Seifert8, Jean C Y Lo2, Dan Quan9, Stephen Borron10, David A Meurer11, Randy I Burnham12, Jude McNally13, Walter Garcia-Ubbelohde14, Victoria E Anderson12. 1. Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO. Electronic address: Richard.dart@rmpdc.org. 2. Loma Linda University, Loma Linda, CA. 3. Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO; Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO. 4. Department of Emergency Medicine, Louisiana State University Health Sciences Center, Shreveport, LA. 5. Department of Emergency Medicine, University of California-Davis, Sacramento, CA. 6. Department of Clinical Emergency Medicine, University of California-San Francisco, Fresno, CA. 7. Division of Medical Toxicology and Departments of Emergency Medicine and Pediatrics, University of Virginia School of Medicine, Charlottesville, VA. 8. University of New Mexico Health Sciences Center and New Mexico Poison and Information Center, Albuquerque, NM. 9. Department of Emergency Medicine, Maricopa Integrated Health System, Phoenix, AZ. 10. Department of Emergency Medicine, Texas Tech University Health Sciences Center, El Paso, TX. 11. Department of Emergency Medicine, University of Florida College of Medicine, Gainesville, FL. 12. Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO. 13. Rare Disease Therapeutics, Inc, Franklin, TN. 14. Instituto Bioclon S.A. de C.V, Tlalpan, Mexico.
Abstract
STUDY OBJECTIVE: The antivenom currently available for treatment of systemic black widow envenomation (latrodectism) is composed of equine whole immunoglobin. Although considered effective, it has been associated with anaphylaxis and 2 reported fatalities. We test the efficacy and safety of new equine antivenom composed of purified F(ab')2 antibody fragments. METHODS: A randomized, double-blind, placebo-controlled trial was conducted at 16 sites across the United States. Subjects aged 10 years or older with moderate to severe pain because of black widow spider envenomation received F(ab')2 antivenom or placebo. The primary outcome measure was treatment failure, which was defined as failure to achieve and maintain clinically significant reduction in pain for 48 hours posttreatment. Secondary measures of pain intensity differences and summed pain intensity difference were computed. Adverse events were recorded. RESULTS: Sixty patients were treated (29 antivenom and 31 placebo). The mean age was 39 years and 68% were male. There were 15 treatment failures in the antivenom group and 24 in the placebo group (P=.019). Differences in pain intensity difference between groups were lower at each postbaseline point, and the mean summed pain intensity difference was greater for the antivenom group (difference 2,133; 95% confidence interval 177 to 4,090). No deaths or serious drug-related adverse events were detected. CONCLUSION: The F(ab')2 antivenom met the predefined primary outcome of reduced treatment failures. Secondary outcomes of pain intensity difference and summed pain intensity difference also supported efficacy. The rate of symptom improvement in the placebo group was higher than expected, which may be related to enrollment criteria or placebo effect.
STUDY OBJECTIVE: The antivenom currently available for treatment of systemic black widow envenomation (latrodectism) is composed of equine whole immunoglobin. Although considered effective, it has been associated with anaphylaxis and 2 reported fatalities. We test the efficacy and safety of new equine antivenom composed of purified F(ab')2 antibody fragments. METHODS: A randomized, double-blind, placebo-controlled trial was conducted at 16 sites across the United States. Subjects aged 10 years or older with moderate to severe pain because of black widow spider envenomation received F(ab')2 antivenom or placebo. The primary outcome measure was treatment failure, which was defined as failure to achieve and maintain clinically significant reduction in pain for 48 hours posttreatment. Secondary measures of pain intensity differences and summed pain intensity difference were computed. Adverse events were recorded. RESULTS: Sixty patients were treated (29 antivenom and 31 placebo). The mean age was 39 years and 68% were male. There were 15 treatment failures in the antivenom group and 24 in the placebo group (P=.019). Differences in pain intensity difference between groups were lower at each postbaseline point, and the mean summed pain intensity difference was greater for the antivenom group (difference 2,133; 95% confidence interval 177 to 4,090). No deaths or serious drug-related adverse events were detected. CONCLUSION: The F(ab')2 antivenom met the predefined primary outcome of reduced treatment failures. Secondary outcomes of pain intensity difference and summed pain intensity difference also supported efficacy. The rate of symptom improvement in the placebo group was higher than expected, which may be related to enrollment criteria or placebo effect.