Scopolamine Treatment for Patients With Organophosphate Poisoning

Sponsor

Assaf-Harofeh Medical Center (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00389259

Collaborator

Israeli MOH (Other), International Diabetes Federation (Other)

Enrollment

Location

Arms

Duration (Months)

1.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neurotoxicity Syndromes	Drug: Placebo	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2007

Anticipated Study Completion Date :

Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A IV Scopolamine 0.25mg in adults and 0.006mg/kg in children Q4h	Drug: Placebo IV placebo q4h
Placebo Comparator: B IV Look alike drug Q 4h	Drug: Placebo IV placebo q4h

Arm

Intervention/Treatment

Experimental: A

IV Scopolamine 0.25mg in adults and 0.006mg/kg in children Q4h

Drug: Placebo

IV placebo q4h

Placebo Comparator: B

IV Look alike drug Q 4h

Drug: Placebo

IV placebo q4h

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)