Scopolamine Treatment for Patients With Organophosphate Poisoning

• ClinicalTrials.gov Identifier: NCT00389259
• Recruitment Status: Withdrawn
• First Posted: October 18, 2006
• Last Update Posted: April 5, 2011
• Sponsor: Assaf-Harofeh Medical Center
• Collaborators: Israeli MOH; International Diabetes Federation
• Information provided by: Assaf-Harofeh Medical Center

Tracking Information

• First Submitted Date: October 17, 2006
• First Posted Date: October 18, 2006
• Last Update Posted Date: April 5, 2011
• Study Start Date: October 2007
• Primary Completion Date: Not Provided

Current Primary Outcome Measures (submitted: November 1, 2007)

• Improvement in neurological status as measured by the Glasgow Coma Scale [ Time Frame: 1 week ]
• Duration of seizures. [ Time Frame: 1 week ]
• Number of days on ventilator [ Time Frame: 1 week ]

Original Primary Outcome Measures (submitted: October 17, 2006)

• Improvement in neurological status as measured by the Glasgow Coma Scale
• Duration of seizures.
• Number of days on ventilator

Current Secondary Outcome Measures (submitted: November 1, 2007)

• Total cumulative dose of atropine [ Time Frame: 1 week ]
• Need for benzodiazepines [ Time Frame: 1 week ]
• Number of days in the ICU [ Time Frame: 2 weeks ]
• Adverse effects and complications [ Time Frame: 2 weeks ]
• Neurological assessment at discharge [ Time Frame: 2 weeks ]
• Neurological assessment 3 month after the exposure [ Time Frame: 3 month ]
• Neuro-cognitive assessment at 3 month [ Time Frame: 3 month ]
• Survival at 24 hours [ Time Frame: 24 hours ]
• Survival to discharge [ Time Frame: 4 weeks ]
• Number of days in hospital [ Time Frame: 4 weeks ]

Original Secondary Outcome Measures (submitted: October 17, 2006)

• Total cumulative dose of atropine
• Need for benzodiazapines
• 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 one month and 3 month
• Survival at 24 hours
• Survival to discharge
• Number of days in hospital

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Scopolamine Treatment for Patients With Organophosphate Poisoning
• Official Title: Scopolamine Treatment for Patients With Organophosphate Poisoning - a Randomized, Double Blind, Placebo-Controlled Study.

Brief 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.

• 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.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Neurotoxicity Syndromes

Intervention

Drug: Placebo

IV placebo q4h

Study Arms

• Experimental: A
  IV Scopolamine 0.25mg in adults and 0.006mg/kg in children Q4h
  Intervention: Drug: Placebo
• Placebo Comparator: B
  IV Look alike drug Q 4h
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Estimated Enrollment (submitted: November 1, 2007): 50
• Original Enrollment: Not Provided
• Estimated Study Completion Date: December 2009
• Primary Completion Date: Not Provided

Eligibility 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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 60 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Israel

Administrative Information

• NCT Number: NCT00389259
• Other Study ID Numbers: 70/04*1
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Not Provided
• Study Sponsor: Assaf-Harofeh Medical Center

Collaborators

• Israeli MOH
• International Diabetes Federation

Investigators

• Principal Investigator: Eran Kozer, MD; Assaf-Harofeh Medical Center

• PRS Account: Assaf-Harofeh Medical Center
• Verification Date: March 2010