Scorpion Sting EnvenomationPhase 2/3NCT00685230
Double-Blind, Alacramyn® vs. Placebo in Pediatric Patients
A Phase 2/3 study testing Antivenin Centruroides (scorpion) equine immune F(ab)2 in people with Scorpion Sting Envenomation, run by Instituto Bioclon S.A. de C.V. at 2 sites in United States.
Trial summary
There is no FDA approved therapy for the treatment of scorpion envenomation, Centruroides scorpion envenomation produces a pattern of neurotoxicity with a spectrum of severity ranging from trivial to life threatening. Read more about this study
- Who is it for?
- Ages 6 months to 18 years
- Conditions the study is for
- Scorpion Sting Envenomation
- What is being tested?
- Antivenin Centruroides (scorpion) equine immune F(ab)2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2004to Oct 2005
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Males and females of 6 months to 18 years of age
- Presenting for emergency treatment within 5 hours with clinically important systemic signs of scorpion sting envenomation.
- Signed written Informed Consent by patient or legal guardian.
- No participation in a clinical drug trial within the last month or concomitantly.
Who cannot join
- Allergy to horse serum.
- Use within the past 24 hours of drugs expected to alter immune response: H1 or H2 blockers, corticosteroids.
- Use of any antivenom within the last month or concomitantly.
- Underlying medical conditions that significantly alter immune response: bone marrow suppression congenital or acquired immuno-deficiency state, chemotherapy and chronic corticosteroid use.
- Allergy to midazolam.
- More than 0.3mg/kg of body weight of midazolam administered during the hour prior to study drug infusion.
- Concurrent medical condition involving a baseline neurologic status mimicking envenomation (chorea, tardive dyskinesia, uncontrolled epilepsy).
- Pregnant and nursing women.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Tucson Medical Center
Tucson, Arizona, 85712
University Medical Center
Tucson, Arizona, 85724
About this study
Official title: Prospective, Randomized, Double-Blind, Controlled Study of Alacramyn® vs. Placebo in Pediatric Patients With Systemic Signs of Scorpion Sting Envenomation
There is no FDA approved therapy for the treatment of scorpion envenomation, Centruroides scorpion envenomation produces a pattern of neurotoxicity with a spectrum of severity ranging from trivial to life threatening. Patients stung by Centruroides scorpions develop a clinical syndrome which may require sedation with benzodiazepines and observation for 6 to 28 hours of intensive care monitoring. A safe therapy is necessary to halt the progression of symptoms early in the clinical course while avoiding the clinical deterioration that can occur en route to a tertiary facility. Alacramyn® is anticipated to be safer and more effective than the present standard of care, midazolam, and faster-acting such that the need for transport of most rural patients will be eliminated and will reduce hospitalization time.
The working hypotheses are as follows:
- The investigational antivenom is safe as treatment of scorpion sting envenomation.
- The investigational antivenom is effective as treatment of scorpion sting envenomation.
Read the detailed description
The purpose of this Prospective, Randomized, Double-Blind, Controlled, Multicenter Treatment Protocol, phase III trial is to examine the safety and efficacy of Alacramyn® for treatment of patients envenomed by scorpion sting.
This study will take place in two pediatric Intensive care units in Tucson, Arizona.
Patients who arrive at the emergency clinic presenting with scorpion sting symptoms will be evaluated for treatment with respect to the inclusion/exclusion criteria according to the study procedures. Only patients with clinically important systemic signs of scorpion sting envenomation will be included in the study. Baseline measures will include severity evaluation of the scorpion sting envenomation. The patient's vital signs, concomitant medication, medical history and demographic data will be collected. Blood tests will be done for haematology, chemistry, venom and anti-venom levels and urine test.
After informed consent and inclusion7exclusion criteria have been obtained and verified, and the baseline measurements have been done, three vials of Alacramyn® or placebo will be administered. During the following 3 hours, midazolam will continue, if indicated for control of agitation.
Patients off midazolam sedation after receiving study drug and no longer manifesting clinically important systemic signs of scorpion envenomation will be discharge at 4 hours, or 2 hours following cessation of midazolam drip, whichever occurs later. Prior to discharge repeat lab work, physical assessments, and vital signs will be done. Patients still requiring midazolam sedation and/or manifesting clinically important systemic signs of scorpion envenomation will be treated with standard of care for the duration of clinical symptoms. Those remaining for extended care undergo final study assessments at time of hospital discharge or at 24 hours after study drug infusion if hospitalization continues.
All patients who participated in the study will be contacted 7 and 14 days after treatment, looking for symptoms suggestive of ongoing venom effect, delayed serum sickness as well as for any other adverse event reported by the patient.
- Conditions
- Scorpion Sting Envenomation
- Being tested
- Antivenin Centruroides (scorpion) equine immune F(ab)2, Placebo
- Keywords
- scorpion sting, envenomation, alacramyn
- Medical subject headings
- Scorpion Stings
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antivenin Centruroides (scorpion) equine immune F(ab)2Biological
Also called Anascorp
3 vials of Alacramyn reconstitued in 50 ml of normal saline as a IV infusion over 10 minutes.
PlaceboOther
Placebo reconstituted in 50 ml of normal saline administered over 10 min
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Alacramyn and midazolam as needed Receives: Biological: Antivenin Centruroides (scorpion) equine immune F(ab)2 |
| 2 | Placebo comparator | placebo and midazolam as needed Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary study endpoint is the resolution of clinically important signs of scorpion envenomation
Measured: 4 hours
Secondary outcomes (2)
Alacramyn®-treated patients require significantly less benzodiazepine sedation than placebo controls, for control of agitation
Measured: 4 hours
Venom blood levels decrease after Alacramyn® treatment, while the placebo group continues to have elevated blood venom levels
Measured: 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2008 (estimated)
- Study startMay 2004
- Primary completionAug 2005
- Study completionOct 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Scorpion Sting EnvenomationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto Bioclon S.A. de C.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Arizona, Universidad Nacional Autonoma de Mexico
- Investigators
- Leslie Boyer, MD, Principal investigator, Poison and Drug CenterWalter Garcia, MD, Study director, Instituto Bioclon S.A. de C.V.Alejandro Alagon, PhD, Study chair, Universidad Nacional Autonoma de Mexico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00685230
- Sponsor's protocol ID
- AL-02/03
- Status last verified
- Jun 2011
- First submitted
- 23 May 2008
- Last updated
- 2 Jun 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Likes K, Banner W Jr, Chavez M. Centruroides exilicauda envenomation in Arizona. West J Med. 1984 Nov;141(5):634-7.
PubMed 6516334Connor, D.A., Seldon, B.S., Scorpion Envenomation. Chapter in Wilderness Medicine; Management of Wilderness and Environmental Emergencies. 3rd edition. Auerbach PS, ed., Mosby Yearbook, Inc. St. Louis, MO. pp 831-842
Gibly R, Williams M, Walter FG, McNally J, Conroy C, Berg RA. Continuous intravenous midazolam infusion for Centruroides exilicauda scorpion envenomation. Ann Emerg Med. 1999 Nov;34(5):620-5. doi: 10.1016/s0196-0644(99)70164-2.
PubMed 10533010Curry SC, Vance MV, Ryan PJ, Kunkel DB, Northey WT. Envenomation by the scorpion Centruroides sculpturatus. J Toxicol Clin Toxicol. 1983-1984;21(4-5):417-49. doi: 10.3109/15563658308990433.
PubMed 6381751Chavez-Haro A., Gonzalez J., Paniagua nJ., Efficiency and Security Comparison between Two Different Scorpion-derived Antivenom in Mexico, Abstract, Leon Study Data Analysis.
Gonzalez, C., et al, Development of an Immunoenzymatic Assay for the Quantification of Scorpion Venom in Plasma, Abstract, Cuernavaca, 2000
LoVecchio F, Welch S, Klemens J, Curry SC, Thomas R. Incidence of immediate and delayed hypersensitivity to Centruroides antivenom. Ann Emerg Med. 1999 Nov;34(5):615-9. doi: 10.1016/s0196-0644(99)70176-9.
PubMed 10533009Alagon Cano, A., Gozalez Juarez, C., From Serotherapy to Fabotherapy, Abstract, Cuernavaca, 1998.
Cabral-Soto, J., et al, Comparison of Efficacy between Two Antiscorpion Antivenoms, Abstract, Cuernavaca, 2000, Clinical Study Report, Randomized, Double-Blind, Variable dosing of Alacramyn in Patients With Scorpion Sting (this was done with two approved products in Mexico, Alacramyn and Birmex), March 2002.
Madrazo Navarro, M., et al, Animales Ponzoñosos en la Población Derechohabiente del IMSS 1990-1996.
Dart, R.C., Horowitz, R.S., Use of Antibodies as Antivenoms: A primitive Solution for Complex Problem? Rocky Mountain Poison and Drug Center, Denver Co, USA.
TESS Data Collection Manual (available upon request)
Berg RA, Tarantino MD. Envenomation by the scorpion Centruroides exilicauda (C sculpturatus): severe and unusual manifestations. Pediatrics. 1991 Jun;87(6):930-3. No abstract available.
PubMed 2034501Rachesky IJ, Banner W Jr, Dansky J, Tong T. Treatments for Centruroides exilicauda envenomation. Am J Dis Child. 1984 Dec;138(12):1136-9. doi: 10.1001/archpedi.1984.02140500042015.
PubMed 6507396Rimsza ME, Zimmerman DR, Bergeson PS. Scorpion envenomation. Pediatrics. 1980 Aug;66(2):298-302.
PubMed 7402816
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Randomized, Double-Blind, Controlled Study of Alacramyn® vs. Placebo in Pediatric Patients With Systemic Signs of Scorpion Sting Envenomation
- ClinicalTrials.gov ID
- NCT00685230
- Acronym / sponsor ID
- AL-02/03
- Conditions
- Scorpion Sting Envenomation
- Keywords
- scorpion sting, envenomation, alacramyn
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Instituto Bioclon S.A. de C.V.Industry (pharma, biotech, devices)
- Collaborators
- University of Arizona, Universidad Nacional Autonoma de Mexico
- Study start
- May 2004
- Primary completion
- Aug 2005 (actual)
- Study completion
- Oct 2005 (actual)
- First posted
- 28 May 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
There is no FDA approved therapy for the treatment of scorpion envenomation, Centruroides scorpion envenomation produces a pattern of neurotoxicity with a spectrum of severity ranging from trivial to life threatening. Patients stung by Centruroides scorpions develop a clinical syndrome which may require sedation with benzodiazepines and observation for 6 to 28 hours of intensive care monitoring. A safe therapy is necessary to halt the progression of symptoms early in the clinical course while avoiding the clinical deterioration that can occur en route to a tertiary facility. Alacramyn® is anticipated to be safer and more effective than the present standard of care, midazolam, and faster-acting such that the need for transport of most rural patients will be eliminated and will reduce hospitalization time.
The working hypotheses are as follows:
- The investigational antivenom is safe as treatment of scorpion sting envenomation.
- The investigational antivenom is effective as treatment of scorpion sting envenomation.
Detailed description
The purpose of this Prospective, Randomized, Double-Blind, Controlled, Multicenter Treatment Protocol, phase III trial is to examine the safety and efficacy of Alacramyn® for treatment of patients envenomed by scorpion sting.
This study will take place in two pediatric Intensive care units in Tucson, Arizona.
Patients who arrive at the emergency clinic presenting with scorpion sting symptoms will be evaluated for treatment with respect to the inclusion/exclusion criteria according to the study procedures. Only patients with clinically important systemic signs of scorpion sting envenomation will be included in the study. Baseline measures will include severity evaluation of the scorpion sting envenomation. The patient's vital signs, concomitant medication, medical history and demographic data will be collected. Blood tests will be done for haematology, chemistry, venom and anti-venom levels and urine test.
After informed consent and inclusion7exclusion criteria have been obtained and verified, and the baseline measurements have been done, three vials of Alacramyn® or placebo will be administered. During the following 3 hours, midazolam will continue, if indicated for control of agitation.
Patients off midazolam sedation after receiving study drug and no longer manifesting clinically important systemic signs of scorpion envenomation will be discharge at 4 hours, or 2 hours following cessation of midazolam drip, whichever occurs later. Prior to discharge repeat lab work, physical assessments, and vital signs will be done. Patients still requiring midazolam sedation and/or manifesting clinically important systemic signs of scorpion envenomation will be treated with standard of care for the duration of clinical symptoms. Those remaining for extended care undergo final study assessments at time of hospital discharge or at 24 hours after study drug infusion if hospitalization continues.
All patients who participated in the study will be contacted 7 and 14 days after treatment, looking for symptoms suggestive of ongoing venom effect, delayed serum sickness as well as for any other adverse event reported by the patient.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: Antivenin Centruroides (scorpion) equine immune F(ab)2Alacramyn and midazolam as needed |
| 2 | Placebo comparator | Other: Placeboplacebo and midazolam as needed |
Who may qualify
- Ages
- 6 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Males and females of 6 months to 18 years of age
- Presenting for emergency treatment within 5 hours with clinically important systemic signs of scorpion sting envenomation.
- Signed written Informed Consent by patient or legal guardian.
- No participation in a clinical drug trial within the last month or concomitantly.
Key exclusion criteria (8 listed)
- Allergy to horse serum.
- Use within the past 24 hours of drugs expected to alter immune response: H1 or H2 blockers, corticosteroids.
- Use of any antivenom within the last month or concomitantly.
- Underlying medical conditions that significantly alter immune response: bone marrow suppression congenital or acquired immuno-deficiency state, chemotherapy and chronic corticosteroid use.
- Allergy to midazolam.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Antivenin Centruroides (scorpion) equine immune F(ab)2Also: Anascorp3 vials of Alacramyn reconstitued in 50 ml of normal saline as a IV infusion over 10 minutes. | Biological | 1 |
| PlaceboPlacebo reconstituted in 50 ml of normal saline administered over 10 min | Other | 2 |
Primary outcome
The primary study endpoint is the resolution of clinically important signs of scorpion envenomation
Time frame: 4 hours
2 secondary outcomes
Alacramyn®-treated patients require significantly less benzodiazepine sedation than placebo controls, for control of agitation
Time frame: 4 hours
Venom blood levels decrease after Alacramyn® treatment, while the placebo group continues to have elevated blood venom levels
Time frame: 1 hour
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2011.
- Background: PubMed 6516334Likes K, Banner W Jr, Chavez M. Centruroides exilicauda envenomation in Arizona. West J Med. 1984 Nov;141(5):634-7.
- BackgroundConnor, D.A., Seldon, B.S., Scorpion Envenomation. Chapter in Wilderness Medicine; Management of Wilderness and Environmental Emergencies. 3rd edition. Auerbach PS, ed., Mosby Yearbook, Inc. St. Louis, MO. pp 831-842
- Background: PubMed 10533010Gibly R, Williams M, Walter FG, McNally J, Conroy C, Berg RA. Continuous intravenous midazolam infusion for Centruroides exilicauda scorpion envenomation. Ann Emerg Med. 1999 Nov;34(5):620-5. doi: 10.1016/s0196-0644(99)70164-2.
- Background: PubMed 6381751Curry SC, Vance MV, Ryan PJ, Kunkel DB, Northey WT. Envenomation by the scorpion Centruroides sculpturatus. J Toxicol Clin Toxicol. 1983-1984;21(4-5):417-49. doi: 10.3109/15563658308990433.
- BackgroundChavez-Haro A., Gonzalez J., Paniagua nJ., Efficiency and Security Comparison between Two Different Scorpion-derived Antivenom in Mexico, Abstract, Leon Study Data Analysis.
- BackgroundGonzalez, C., et al, Development of an Immunoenzymatic Assay for the Quantification of Scorpion Venom in Plasma, Abstract, Cuernavaca, 2000
- Background: PubMed 10533009LoVecchio F, Welch S, Klemens J, Curry SC, Thomas R. Incidence of immediate and delayed hypersensitivity to Centruroides antivenom. Ann Emerg Med. 1999 Nov;34(5):615-9. doi: 10.1016/s0196-0644(99)70176-9.
- BackgroundAlagon Cano, A., Gozalez Juarez, C., From Serotherapy to Fabotherapy, Abstract, Cuernavaca, 1998.
- BackgroundCabral-Soto, J., et al, Comparison of Efficacy between Two Antiscorpion Antivenoms, Abstract, Cuernavaca, 2000, Clinical Study Report, Randomized, Double-Blind, Variable dosing of Alacramyn in Patients With Scorpion Sting (this was done with two approved products in Mexico, Alacramyn and Birmex), March 2002.
- BackgroundMadrazo Navarro, M., et al, Animales Ponzoñosos en la Población Derechohabiente del IMSS 1990-1996.
- BackgroundDart, R.C., Horowitz, R.S., Use of Antibodies as Antivenoms: A primitive Solution for Complex Problem? Rocky Mountain Poison and Drug Center, Denver Co, USA.
- BackgroundTESS Data Collection Manual (available upon request)
- The University of ArizonaLink provided by the sponsor.
- Instituto de Biotecnologia de la UNAMLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leslie Boyer, MD principal investigator
Poison and Drug Center
Walter Garcia, MD study director
Instituto Bioclon S.A. de C.V.
Alejandro Alagon, PhD study chair
Universidad Nacional Autonoma de Mexico
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Antivenin Centruroides (scorpion) equine immune F(ab)2 in people with Scorpion Sting Envenomation, run by Instituto Bioclon S.A. de C.V. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary study endpoint is the resolution of clinically important signs of scorpion envenomation (time frame: 4 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00685230, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2011.