Black Widow Spider Antivenin for Patients With Systemic Latrodectism (BWSP3)
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Phase III Multicenter Clinical Trial of Analatro® [Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2] in Patients With Systemic Latrodectism|
- Proportion of Treatment Failures [ Time Frame: From start of Dose 1 infusion to 48 hours post treatment ]
The primary efficacy endpoint for this study was the proportion of subjects in which pain control was not achieved 48 hours post-study drug infusion as identified by treatment failure. A treatment failure was defined as a subject who did not achieve pain control during the treatment phase, up to 48 hours after Dose 1 infusion start time. Subjects were deemed treatment failures if they met one or more of the following criteria:
- Subject did not complete the treatment phase due to absence of clinically significant improvement in pain intensity relative to baseline at 60, 90, 120, or 150 minutes post start of Dose 1.
- Subject required treatment with commercially available antivenin or prescription pain medication for signs and symptoms associated with latrodectism at any time during the treatment phase up to 48 hours after Dose 1 infusion start time.
- Reduction in Pain Intensity [ Time Frame: 30 minutes post treatment ]The proportion of patients with a clinically significant decrease in pain intensity at 30 minutes post-treatment (after Dose 1 and Dose 2, as applicable) will be measured by the patient's self-assessment of pain intensity using the visual analog scale (VAS). A clinically significant reduction in pain is defined as a decrease in VAS scores of greater than or equal to 13 mm.
- Drug-related Adverse Events [ Time Frame: Start of Dose 1 through 17 days post treatment ]To evaluate safety of Analatro, the proportion of subjects experiencing at least one adverse event (AE) that was determined to be related to study drug was computed for each treatment group. All AEs classified as definitely or possibly related to study drug were considered drug-related.
- Reduction in Pain Intensity [ Time Frame: Start of Dose 1 to any post-infusion time point ]The proportion of patients with a clinically significant decrease in pain intensity relative to baseline at any time point during the treatment phase was measured by the patient's self-assessment of pain intensity using the visual analog scale (VAS). A clinically significant reduction in pain was defined as a decrease in VAS scores of greater than or equal to 13 mm.
- Drug-related Serious Adverse Events [ Time Frame: Start of Dose 1 through 17 days post treatment ]The proportion of subjects with drug-related serious adverse events.
|Study Start Date:||August 2009|
|Study Completion Date:||October 2014|
|Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2
30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses
Placebo Comparator: 2
50 mL of saline infused over 10 minutes
Other Name: Placebo
Hide Detailed Description
Instituto Bioclon S.A. de C.V. has developed Analatro®, an antibody fragment (Fab2) containing widow spider (Latrodectus) antivenom, and proposes to conduct a clinical trial in hospital emergency departments to assess the efficacy and safety of this product in patients with moderate to severe pain associated with Latrodectus envenomation (latrodectism). The primary objectives of this Phase III, multi-center, double-blind, controlled study are as follows:
To determine the efficacy of Analatro compared to control for the treatment of latrodectism as measured by the proportion of patients in whom pain control is not achieved (e.g., treatment failure)
To further characterize the safety profile of Analatro, including comparison of the rate of drug-related adverse events to control for the treatment of latrodectism
The flow of study procedures are illustrated in the chart on the following page. All patients who consent to participate will be given a visual analog scale (VAS, 0=no pain to 100mm=worst possible pain) for assessing pain intensity. Patients that meet all study enrollment requirements, including a minimum age of 10 years, a clinical diagnosis of latrodectism and a VAS pain score of ≥40 mm (moderate to severe pain) will be randomly assigned to be treated with Analatro or control. A screening phase will be completed, during which time preliminary procedures will be performed by the investigator (medical history, physical exam, and pregnancy test as applicable) and two doses of Analatro or two doses of saline control will be prepared. Fentanyl may be administered intravenously as needed for pain relief during the screening phase at a dosage not to exceed 1.5 µg/kg/hr. At the end of the screening phase, baseline measurements (vital signs, VAS pain score) will be performed. Patients must have a baseline VAS score ≥40 mm to receive study medication.
Eligible patients will begin a 2.5 hour treatment phase. Dose 1 of study medication (50 mL) will be infused intravenously over 10 minutes. Thirty minutes after the start of Dose 1, pain intensity will be assessed (VAS2), vital signs will be recorded (VS2), and a blood sample collected (B2). Clinical improvement in this study will be defined as a VAS score that is at least 13mm less than the baseline VAS score (VAS1). Patients that fail to show clinical improvement at 30 minutes will receive Dose 2 of study medication (Dose 2 will be identical to Dose 1). Patients showing clinical improvement will not receive Dose 2.
Thirty minutes after VAS2 (or after the start of Dose 2, if applicable), VAS3 will be administered, vital signs (VS3) will be recorded, and a blood sample (B3) will be collected. If the patient has not clinically improved relative to baseline, the patient will be deemed a treatment failure; the treatment phase will be discontinued, and the patient will be treated in accordance with standard of care by the investigator and/or treating physician. Patients that have clinically improved will remain in the treatment arm.
The remaining 1.5 hours of the treatment arm will consist of serial assessments of pain intensity (VAS4, 5 and 6), vital signs (VS4, 5 and 6), and collection of one blood sample (B4, 5 and 6) every 30 minutes. After each VAS, the patient must continue to show clinical improvement relative to baseline to remain in the treatment arm. Otherwise, the patient will exit the treatment phase and be treated in accordance with standard of care. No analgesics will be allowed during the treatment phase to eliminate the potential confounding effect of pain medication on assessing the effectiveness of the study medication on clinical improvement. Routine decision points for treatment failure (every thirty minutes) will promote accurate identification of treatment failures without compromising timely provision of pain medication in absence of clinical improvement.
All patients will be closely monitored for adverse events during Dose 1 of treatment until the time of discharge from the emergency department. Follow-up for possible adverse events and recurring/residual symptoms will be conducted by telephone on Days 2, 10, and 17 after discharge from the emergency department.
Treatment failure will be defined as (1) early exit from the treatment phase due to absence of clinical improvement relative to baseline and/or (2) patient requires prescription pain medication or Antivenin Latrodectus Mactans (Merck) for pain associated with the study condition being treated at any time after the treatment phase up to 48 hours after the time of discharge from the emergency department. To improve accurate identification of treatment failure after discharge, no preventative pain medication will be administered or prescribed to patients that successfully complete the treatment phase. Patients will be encouraged to call the investigator or return to the emergency department, if necessary, for proper evaluation and treatment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00657540
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00657540
|United States, Arizona|
|Banner Good Samaritan Medical Center|
|Phoenix, Arizona, United States, 85006|
|Maricopa Medical Center|
|Phoenix, Arizona, United States, 85008|
|United States, California|
|University of California Davis|
|Davis, California, United States, 95616|
|University California San Francisco - Fresno|
|Fresno, California, United States, 93701|
|University of California Irvine|
|Irvine, California, United States, 92697|
|Loma Linda University|
|Loma Linda, California, United States, 92354|
|University of California San Diego|
|San Diego, California, United States, 92103|
|San Diego Children's Hospital|
|San Diego, California, United States, 92123|
|United States, Colorado|
|University of Colorado Hospital|
|Aurora, Colorado, United States, 80010|
|Denver Health and Hospital Authority|
|Denver, Colorado, United States, 80204|
|United States, Florida|
|Cape Coral Hospital|
|Cape Coral, Florida, United States, 33990|
|University of Florida, Department of Emergency Medicine|
|Gainesville, Florida, United States, 32610|
|United States, Louisiana|
|LSU Health Sciences|
|Shreveport, Louisiana, United States, 71106|
|United States, New Mexico|
|University of New Mexico|
|Albuquerque, New Mexico, United States, 87131|
|United States, Texas|
|Texas Tech - West Texas Regional Poison Center|
|El Paso, Texas, United States, 79905|
|United States, Virginia|
|University of Virginia Health System|
|Charlottesville, Virginia, United States, 22908|
|Principal Investigator:||Richard C Dart, MD, PhD||Rocky Mountain Poison & Drug Center - Denver Health|
|Study Director:||Walter Garcia, MD||Instituto Bioclon S.A. de C.V.|