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Study to Know the Efficacy of Higher Doses of Pralidoxime in Patients of Organophpsphorus Poisoning.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00333944
Recruitment Status : Completed
First Posted : June 6, 2006
Last Update Posted : June 6, 2006
Information provided by:
Giriraj Hospital

Brief Summary:
The purpose of this study is to determine whether high doses of pralidoxime(PAM) are effective as compare to lower doses of PAM in the management of moderately sever organophosphorus poisoning patients.

Condition or disease Intervention/treatment Phase
Acute Organophosphorus Pesticide Poisoning Drug: Pralidoxime(drug) Not Applicable

Detailed Description:

Standard treatment of organophosphorus pesticide poisoning involves administration of intravenous atropine and oximes to counter acetylcholinesterase inhibition.1 Treatment with atropine is well established, but the efficacy and dosage schedule of oximes are controversial.2-5 A dose of 1g every four to six hours has been the standard regimen in Asian district hospitals but many clinicians remain unconvinced by its effectiveness.3 Randomised controlled trials (RCT) performed in Vellore during the nineties compared a 12g infusion over 3-4 days with a 1g bolus dose and then with placebo.6,7 The authors reported no benefit from pralidoxime and an increased mortality in those receiving the infusion, and have stated that pralidoxime should not be given to organophosphorus poisoned patients.2

Others consider that the dosage regimen was not ideal, with therapeutic concentrations being obtained rarely during the treatment.3,4 Furthermore, many patients presented late and had taken dimethyl pesticides - a class that does not respond well to oximes after several hours - biasing the study against finding benefit.

The proposed minimum effective plasma levels for pralidoxime of 4 mg/L were based on in vitro and animal experiments by Sundwall.8 Recent evidence, however, suggests that higher blood concentrations of pralidoxime are needed to antagonise the toxic effects of many pesticides and that a bolus loading infusion followed by a maintenance infusion would be the best regimen.9 The WHO have proposed that patients receive around 30mg/kg pralidoxime salt as a loading dose followed by an infusion of at least 8mg/kg/hr (roughly equivalent to 1-2 g bolus followed by 0·5 g/h in a 50kg south Asian patient).9,10 However, no trials have yet been performed to determine whether such a regimen reduces morbidity and mortality in severely poisoned patients.3 Since organophosphorus pesticides kill hundreds of thousands of people in rural Asia every year, it is essential to determine whether it benefits or harms such poisoned patients.

Our hospital has typically used a regimen of 1g q4h in organophosphorus poisoned patients but we were unconvinced about the effectiveness of this expensive drug since many patients required ventilation for >10 days. We informally treated several patients with the WHO-recommended regimen but saw little benefit. Since pralidoxime has a high therapeutic index, we then decided to conduct a RCT with still higher doses, i.e. to compare a 1 g infusion every hour (q1h, 24 g/day) with 1g every four hours (q4h, 6 g/day), after a 2 g loading dose, to assess the effectiveness of high dose pralidoxime in organophosphorus poisoned patients.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effectiveness of High Dose Pralidoxime in the Treatment of Organophosphorus Pesticide Poisoning - a Randomised Controlled Trial
Study Start Date : May 2000
Study Completion Date : June 2003

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pesticides Poisoning

Primary Outcome Measures :
  1. Median atropine dose required in first 24 hours
  2. proportion of patients who required intubation or developed intermediate syndrome
  3. number of days ventilated and required ICU care

Secondary Outcome Measures :
  1. pneumonia (aspiration or ventilator-associated)
  2. mean systolic and diastolic blood pressure (BP) in first 24 hours
  3. case fatality

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

-patients with a history of poisoning by an organophosphorus pesticide and clinical features of poisoning.

Exclusion Criteria:

patients who

  • were under 12 years
  • had chronic disease
  • had malignancy
  • were pregnant,
  • presented more than 24 hrs post-ingestion,
  • who could not be resuscitated successfully in the emergency room of our ospital

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00333944

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Giriraj Hospital and Intensive Care Unit.
Baramati. Pune District., Maharashtra., India, 413 102.
Sponsors and Collaborators
Giriraj Hospital
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Principal Investigator: Kirti S Pawar, MBBS,DA
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information Identifier: NCT00333944    
Other Study ID Numbers: GRH/IERC/2000/12
First Posted: June 6, 2006    Key Record Dates
Last Update Posted: June 6, 2006
Last Verified: May 2000
Keywords provided by Giriraj Hospital:
Organophosphorus poisoning
Intermediate syndrome.
Additional relevant MeSH terms:
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Chemically-Induced Disorders
Protective Agents
Physiological Effects of Drugs
Cholinesterase Reactivators
Enzyme Reactivators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents