ClinicalTrials.gov
ClinicalTrials.gov Menu

Black Widow Spider Antivenin for Patients With Systemic Latrodectism (BWSP3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00657540
Recruitment Status : Completed
First Posted : April 14, 2008
Results First Posted : September 18, 2017
Last Update Posted : April 3, 2018
Sponsor:
Collaborator:
Rare Disease Therapeutics Inc.
Information provided by (Responsible Party):
Instituto Bioclon S.A. de C.V.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Latrodectism
Interventions Drug: Analatro
Drug: Saline
Enrollment 60

Recruitment Details Due to the nature of the treatment emergent condition of interest, no patients were actively recruited. Potential subjects presenting with moderate to severe pain associated with diagnosed latrodectism were evaluated at 16 sites across the United States. The first subject was enrolled on 10/08/09. The last subject completed the study on 10/27/14.
Pre-assignment Details  
Arm/Group Title Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Normal Saline
Hide Arm/Group Description

Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2

Analatro: 30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses

Normal Saline

Saline: 50 mL of saline infused over 10 minutes

Period Title: Overall Study
Started 29 31
Completed 28 [1] 27 [1]
Not Completed 1 4
Reason Not Completed
Lost to Follow-up             1             4
[1]
All subjects had a known treatment failure disposition at time of loss to follow-up.
Arm/Group Title Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Normal Saline Total
Hide Arm/Group Description

Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2

Analatro: 30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses

Normal Saline

Saline: 50 mL of saline infused over 10 minutes

Total of all reporting groups
Overall Number of Baseline Participants 29 31 60
Hide Baseline Analysis Population Description
The analysis population consists of all patients that were randomized and received any study drug (modified intent-to-treat population).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 29 participants 31 participants 60 participants
37.3  (15.18) 41.0  (17.84) 39.2  (16.57)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 31 participants 60 participants
Female
11
  37.9%
8
  25.8%
19
  31.7%
Male
18
  62.1%
23
  74.2%
41
  68.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 31 participants 60 participants
Hispanic or Latino
13
  44.8%
17
  54.8%
30
  50.0%
Not Hispanic or Latino
16
  55.2%
14
  45.2%
30
  50.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 31 participants 60 participants
American Indian or Alaska Native
3
  10.3%
0
   0.0%
3
   5.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
   6.9%
0
   0.0%
2
   3.3%
White
14
  48.3%
20
  64.5%
34
  56.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
10
  34.5%
11
  35.5%
21
  35.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 29 participants 31 participants 60 participants
29
 100.0%
31
 100.0%
60
 100.0%
Baseline VAS Pain Score (mm)   [1] 
Mean (Standard Deviation)
Unit of measure:  Mm
Number Analyzed 29 participants 31 participants 60 participants
79.7  (13.16) 73.8  (16.14) 76.7  (14.96)
[1]
Measure Description: The Visual Analog Scale (VAS) ranged from 0 (no pain) to 100 mm (worst possible pain).
1.Primary Outcome
Title Number of Participants With Treatment Failure
Hide Description

The primary efficacy endpoint for this study was the number 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.
Time Frame From start of Dose 1 infusion to 48 hours post treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of all subjects that were randomized and received any study drug (modified intent to treat population).
Arm/Group Title Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Normal Saline
Hide Arm/Group Description:

Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2

Analatro: 30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses

Normal Saline

Saline: 50 mL of saline infused over 10 minutes

Overall Number of Participants Analyzed 29 31
Measure Type: Count of Participants
Unit of Measure: Participants
15
  51.7%
24
  77.4%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2, Normal Saline
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0185
Comments [Not Specified]
Method Chi-squared
Comments The proportion of treatment failures was compared between groups using a one-sided test at the 0.025 level of significance.
2.Secondary Outcome
Title Number of Participants With at Least 13 mm Reduction in Pain Score at 30 Minutes Post-Treatment
Hide Description The number 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. The VAS ranged from 0 (no pain) to 100 mm (worst possible pain).
Time Frame 30 minutes post treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Normal Saline
Hide Arm/Group Description:

Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2

Analatro: 30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses

Normal Saline

Saline: 50 mL of saline infused over 10 minutes

Overall Number of Participants Analyzed 29 31
Measure Type: Count of Participants
Unit of Measure: Participants
13
  44.8%
11
  35.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2, Normal Saline
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2302
Comments [Not Specified]
Method Chi-squared
Comments Chi-squared tests at the 0.025 level of significance were used to test for a difference in proportions between the treatment groups.
3.Secondary Outcome
Title Drug-related Adverse Events
Hide Description To evaluate safety of Analatro, the number 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.
Time Frame Start of Dose 1 through 17 days post treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Normal Saline
Hide Arm/Group Description:

Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2

Analatro: 30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses

Normal Saline

Saline: 50 mL of saline infused over 10 minutes

Overall Number of Participants Analyzed 29 31
Measure Type: Count of Participants
Unit of Measure: Participants
16
  55.2%
18
  58.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2, Normal Saline
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8213
Comments [Not Specified]
Method Chi-squared
Comments The proportion of subjects with at least one drug-related adverse event by treatment groups using a two-sided test at the 0.05 level of significance.
4.Secondary Outcome
Title Number of Participants With at Least 13 mm Reduction in Pain Score at Any Time Point
Hide Description The number 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. The VAS ranged from 0 (no pain) to 100 mm (worst possible pain).
Time Frame Start of Dose 1 to any post-infusion time point
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Normal Saline
Hide Arm/Group Description:

Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2

Analatro: 30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses

Normal Saline

Saline: 50 mL of saline infused over 10 minutes

Overall Number of Participants Analyzed 29 31
Measure Type: Count of Participants
Unit of Measure: Participants
19
  65.5%
18
  58.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2, Normal Saline
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2765
Comments [Not Specified]
Method Chi-squared
Comments The proportion of subjects with decreased pain at any time point between treatment groups using a one-sided test at the 0.025 level of significance.
5.Secondary Outcome
Title Drug-related Serious Adverse Events
Hide Description The number of subjects with drug-related serious adverse events.
Time Frame Start of Dose 1 through 17 days post treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Normal Saline
Hide Arm/Group Description:

Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2

Analatro: 30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses

Normal Saline

Saline: 50 mL of saline infused over 10 minutes

Overall Number of Participants Analyzed 29 31
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
Time Frame Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Normal Saline
Hide Arm/Group Description

Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2

Analatro: 30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses

Normal Saline

Saline: 50 mL of saline infused over 10 minutes

All-Cause Mortality
Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Normal Saline
Affected / at Risk (%) Affected / at Risk (%)
Total   0/29 (0.00%)      0/31 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Normal Saline
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/29 (0.00%)      2/31 (6.45%)    
Injury, poisoning and procedural complications     
Inadequate Pain Control * 1 [1]  0/29 (0.00%)  0 1/31 (3.23%)  1
Skin and subcutaneous tissue disorders     
Cellulitis * 1 [2]  0/29 (0.00%)  0 1/31 (3.23%)  1
1
Term from vocabulary, MedDRA 17.0
*
Indicates events were collected by non-systematic assessment
[1]
A subject was hospitalized for inadequate pain control 24 hours after receiving placebo. The subject was treated with analgesics and was discharged after 3 days of hospitalization. This event was determined to not be related to study drug.
[2]
A subject was hospitalized for the treatment of cellulitis after receiving placebo. The subject had a previous history of methicillin-resistant staphylococcus aureus related to cellulitis. The event was determined to be not related to study drug.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Normal Saline
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   26/29 (89.66%)      27/31 (87.10%)    
Gastrointestinal disorders     
Constipation * 1  0/29 (0.00%)  6/31 (19.35%) 
Nausea * 1  3/29 (10.34%)  1/31 (3.23%) 
Vomiting * 1  1/29 (3.45%)  2/31 (6.45%) 
General disorders     
Chills * 1  3/29 (10.34%)  7/31 (22.58%) 
Fatigue * 1  1/29 (3.45%)  2/31 (6.45%) 
Inflammation * 1  2/29 (6.90%)  0/31 (0.00%) 
Pyrexia * 1  2/29 (6.90%)  4/31 (12.90%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  1/29 (3.45%)  2/31 (6.45%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  7/29 (24.14%)  6/31 (19.35%) 
Myalgia * 1  3/29 (10.34%)  4/31 (12.90%) 
Pain in extremity * 1  4/29 (13.79%)  3/31 (9.68%) 
Nervous system disorders     
Headache * 1  5/29 (17.24%)  4/31 (12.90%) 
Paraesthesia * 1  3/29 (10.34%)  0/31 (0.00%) 
Psychiatric disorders     
Anxiety * 1  0/29 (0.00%)  2/31 (6.45%) 
Insomnia * 1  1/29 (3.45%)  3/31 (9.68%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  1/29 (3.45%)  2/31 (6.45%) 
Skin and subcutaneous tissue disorders     
Pruritus * 1  18/29 (62.07%)  17/31 (54.84%) 
Rash * 1  4/29 (13.79%)  8/31 (25.81%) 
Urticaria * 1  2/29 (6.90%)  0/31 (0.00%) 
1
Term from vocabulary, MedDRA 17.0
*
Indicates events were collected by non-systematic assessment
The study is limited by the small sample size; however this trial was powered appropriately for an orphan indication. The study is also limited by the difficulty in confirming latrodectism without a spider or clear history of seeing a spider.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Victoria Anderson - Research Projects Manager
Organization: Rocky Mountain Poison and Drug Center
Phone: 303-389-1236
Responsible Party: Instituto Bioclon S.A. de C.V.
ClinicalTrials.gov Identifier: NCT00657540     History of Changes
Other Study ID Numbers: XF-07/03
First Submitted: April 9, 2008
First Posted: April 14, 2008
Results First Submitted: August 16, 2017
Results First Posted: September 18, 2017
Last Update Posted: April 3, 2018