Affinity-Purified, Mixed Monospecific Crotalid Antivenom Ovine Fab for the Treatment of Crotalid Venom Poisoning,☆☆,,★★

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Abstract

Study objective: To test the efficacy and safety of a new antivenom, affinity-purified, mixed monospecific crotalid antivenom ovine Fab, in human subjects with minimal or moderate crotalid envenomation. Methods: We conducted a prospective multicenter clinical trial of 11 patients 10 years or older with progressive manifestations after mild to moderate crotalid snakebite. After giving their consent, subjects received four to eight vials of study drug and were then repeatedly examined over 48 hours and at 7 and 14 days after discharge. Each patient's clinical condition was evaluated serially with the use of a validated severity score, as well as on the basis of the investigator's assessment. Results: In all 11 subjects the antivenom was judged by the investigator to have had a beneficial response. The severity score for each patient remained the same or decreased over the first 4 hours. However, two subjects demonstrated worsened condition 12 to 15 hours after antivenom administration. In no subject did an allergic reaction develop. Conclusion: In this patient group, affinity-purified, mixed monospecific crotalid antivenom ovine Fab was associated with a halt of progressive crotalid venom poisoning. Initial safety data are promising but must be addressed further in subsequent studies. [Dart RC, Seifert SA, Carroll L, Clark RF, Hall E, Boyer-Hassen LV, Curry SC, Kitchens CS, Garcia RA: Affinity-purified, mixed monospecific crotalid antivenom ovine Fab for the treatment of crotalid venom poisoning.Ann Emerg Med July 1997;30:33-39.]

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INTRODUCTION

Crotalid snakebite is an unusual but important cause of injury in the United States. Rattlesnakes and cottonmouth and copperhead snakes inhabit nearly every state and bite approximately 7,000 people each year, resulting in several deaths.1

Antivenin (Crotalidae) Polyvalent [Wyeth] is the only antidote commercially available for the treatment of crotalid bite. Although the Wyeth antivenom was a major advance when introduced 40 years ago, it is well known that the antivenom causes serious adverse

MATERIALS AND METHODS

Eleven patients were enrolled in this prospective, open-label, multicenter trial from August through November 1993 (Figure). The study was approved by the institutional review board at each site. After enrollment and standardized initial assessment (history, physical examination, and laboratory tests) and informed consent, each patient received an intravenous dose of the study antivenom. The data included in this report were collected directly from case report forms completed by each

RESULTS

Eleven patients were enrolled (Table 1); all met the inclusion criteria for evaluation of efficacy. No patient was excluded. Five patients received four vials and six patients received eight vials of study antivenom. The mean severity score for all patients was 3.9±2.2 (mean±SD) before antivenom administration; 12 hours after administration the mean score was 2.6±1.0 (Table 2).

The investigators judged that all patients were clinically improved after antivenom infusion. Examination of individual

DISCUSSION

In 1985, Lindsey challenged the use of Wyeth antivenom because no controlled study of efficacy and safety had been performed.10 Our trial provides the first prospective evidence in human subjects that antivenom may be an effective treatment for venom poisoning caused by North American crotalid snakes. We used a validated severity score, as well as the investigator's clinical assessment: a clinically relevant, albeit more subjective, judgment. Both measures indicated that all patients were

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    The typical initial dosing of CroFab is 4 to 6 vials; however, the starting dose may vary from 4 to 12 vials based on the clinical judgement and severity of envenomation. In the initial studies of FabAV, “initial control,” defined as a halting of progressive local effects and resolution of hematologic and systemic toxicity, was achieved in 98% of patients (37,38). In 95% of patients, initial control was achieved within 1 h of administration.

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From the Rocky Mountain Poison and Drug Center, Denver Health,* and the University of Colorado Health Sciences Center, Denver, CO; the Department of Emergency Medicine, Kino Community Hospital,§ and the Departments of Pediatrics and Clinical Medicine, University of Arizona College of Medicine, Tucson, AZ; the Department of Medical Toxicology, Good Samaritan Regional Medical Center,# Phoenix, AZ; the San Diego Regional Poison Center** and the University of California,‡‡ San Diego, CA; John D Archbold Memorial Hospital, Thomasville, GA;§§ and the Veterans Administration Hospital, Gainesville, FL.∥∥

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Supported by US Food and Drug Administration Orphan Product Development grant FD-R-000945-01-1.

Reprint no. 47/1/82666

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Address for reprints: Richard C Dart, MD, PhD, Rocky Mountain Poison and Drug Center, 8802 East Ninth Avenue, Denver, CO 80220, 303-739-1100, Fax 303-739-1119, E-mail [email protected]

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