Scopolamine Treatment for Patients With Organophosphate Poisoning
Information source: Assaf-Harofeh Medical Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Neurotoxicity Syndromes
Intervention: Placebo (Drug)
Phase: N/A
Status: Withdrawn
Sponsored by: Assaf-Harofeh Medical Center Official(s) and/or principal investigator(s): Eran Kozer, MD, Principal Investigator, Affiliation: Assaf-Harofeh Medical Center
Summary
Organophosphate (OP) compounds are a major threat as chemical warfare agents or in terrorist
act. OPs are also the active ingredient of many insecticides. Ingestion of insecticides is a
common cause of death among people who commit suicide in developing countries. OPs poisoning
also frequently occurs after accidental exposure to agricultural OPs and in children as a
result of unintentional ingestion.
The use of competitive inhibitors of acetylcholine other than atropine for patient with
organophosphate (OP) poisoning is controversial. Because scopolamines' ability to cross the
blood brain barrier is better than atropine, it has been suggested that scopolamine should
be used OP poisoned patients who have central nervous system (CNS) manifestations. However
there is controversy regarding its potential benefit in the treatment of organophosphate
poisoning in humans. To the best of our knowledge there are no randomised controlled studies
on the use of scopolamine in humans. This prospective randomised controlled study is aimed
to determine whether adding scopolamine to the standard treatment of atropine and oximes in
patients with CNS symptoms of OP poisoning improve the outcome.
Clinical Details
Official title: Scopolamine Treatment for Patients With Organophosphate Poisoning - a Randomized, Double Blind, Placebo-Controlled Study.
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Improvement in neurological status as measured by the Glasgow Coma ScaleDuration of seizures. Number of days on ventilator
Secondary outcome: Total cumulative dose of atropineNeed for benzodiazepines Number of days in the ICU Adverse effects and complications Neurological assessment at discharge Neurological assessment 3 month after the exposure Neuro-cognitive assessment at 3 month Survival at 24 hours Survival to discharge Number of days in hospital
Detailed description:
Objective: to determine whether adding scopolamine to the standard treatment of atropine and
oximes improve the outcome of patients with OP poisoning and CNS manifestations. Design: A
multi-center, randomized, double blind, placebo controlled study. Setting: Emergency
Departments & Intensive Care Units in Israel. Participants: Patients 2 - 60 years old with
acute OP poisoning and CNS manifestations. Interventions: In addition to standard treatment
with atropine and obidoxime, eligible patients will be randomly assigned to one of two
treatment groups, scopolamine group, and placebo group (both given in the same volume).
Scopolamine will be given IM or IV in a dose of 0. 25mg for adults and 0. 006mg/kg for
children every 4 hours. At least three doses of scopolamine (or placebo) will be given. The
medical staff will be blinded to the treatment given. Main outcome measures: Improvement in
neurological status, duration of seizures and number of days on ventilator. Data analysis:
The main outcome measures, will be compared using the Student's t-test or the Mann-Whitney
tests as appropriate. The *2 or Fisher Exact tests, as appropriate, will be used for
comparisons of categorical variables. We will use multiple logistic regression to examine
the extent to which variables predict success or failure of the treatment.
Eligibility
Minimum age: 2 Years.
Maximum age: 60 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Age: 2- 60 years
- At least two of the following three criteria:
- Known exposure to an organophosphate or carbamate insecticide in the last 72
hours.
- Symptoms and signs typical to organophosphate poisoning involving at least two
systems (gastrointestinal, respiratory, skin, eyes,) See appendix
- Low levels of plasma butyrylcholinesterase (less than 50% of the lower normal
range )
- CNS involvement in the first 72 hours after exposure: determined by finding at least
one of the following major criteria or at least two of the minor criteria
Major criteria for CNS involvement:
- Seizures
- Extrapyramidal or Parkinson like symptoms
- Decreased level of consciousness (GCS< 12)
Minor criteria for CNS involvement:
- GCS 14-12
- Confusion
- Hallucinations
Exclusion Criteria:
- Hypersensitivity to scopolamine
- Glaucoma, narrow-angle (angle-closure)
- Tachyarrhythmias, congestive heart failure
- Obstructive gastrointestinal disease
- Myasthenia Gravis
- Reflux esophagitis
- Ulcerative colitis
- Known obstructive uropathy
- Pregnancy
- Patient or legal guardian unable to give informed consent (see comment under ethics)
- Severe co-morbidity (multi-trauma, advanced cancer, etc)
Locations and Contacts
Rambam Hospital, Haifa, Israel
Additional Information
Starting date: October 2007
Last updated: April 4, 2011
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