Scopolamine Treatment for Patients With Organophosphate Poisoning

Neurotoxicity Syndromes Clinical Trial

Official title:

Scopolamine Treatment for Patients With Organophosphate Poisoning - a Randomized, Double Blind, Placebo-Controlled Study.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00389259
• Other study ID #: 70/04*1
• Status: Withdrawn
• Phase: N/A
• First received: October 17, 2006
• Last updated: April 4, 2011
• Start date: October 2007
• Est. completion date: December 2009

Study information

• Verified date: March 2010
• Source: Assaf-Harofeh Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Israeli Health Ministry Pharmaceutical Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 50
• Est. completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 60 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neurotoxicity Syndromes
• Organophosphate Poisoning

Intervention

Drug:
• Placebo
IV placebo q4h

Locations

Country	Name	City	State
Israel	Rambam Hospital	Haifa

Sponsors (3)

Lead Sponsor	Collaborator
Assaf-Harofeh Medical Center	International Diabetes Federation, Israeli MOH

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in neurological status as measured by the Glasgow Coma Scale		1 week
Primary	Duration of seizures.		1 week
Primary	Number of days on ventilator		1 week
Secondary	Total cumulative dose of atropine		1 week
Secondary	Need for benzodiazepines		1 week
Secondary	Number of days in the ICU		2 weeks
Secondary	Adverse effects and complications		2 weeks
Secondary	Neurological assessment at discharge		2 weeks
Secondary	Neurological assessment 3 month after the exposure		3 month
Secondary	Neuro-cognitive assessment at 3 month		3 month
Secondary	Survival at 24 hours		24 hours
Secondary	Survival to discharge		4 weeks
Secondary	Number of days in hospital		4 weeks