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Scopolamine Treatment for Patients With Organophosphate Poisoning

S

Shamir Medical Center (Assaf-Harofeh)

Status

Withdrawn

Conditions

Neurotoxicity Syndromes

Treatments

Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT00389259
70/04*1

Details and patient eligibility

About

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.

Full 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.

Enrollment

50 estimated patients

Sex

All

Ages

2 to 60 years old

Volunteers

No 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)

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

50 participants in 2 patient groups, including a placebo group

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

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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