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

June 5, 2006 updated by: Giriraj Hospital

Effectiveness of High Dose Pralidoxime in the Treatment of Organophosphorus Pesticide Poisoning - a Randomised Controlled Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment

200

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Maharashtra.
      • Baramati. Pune District., Maharashtra., India, 413 102.
        • Giriraj Hospital and Intensive Care Unit.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Median atropine dose required in first 24 hours
proportion of patients who required intubation or developed intermediate syndrome
number of days ventilated and required ICU care

Secondary Outcome Measures

Outcome Measure
pneumonia (aspiration or ventilator-associated)
mean systolic and diastolic blood pressure (BP) in first 24 hours
case fatality

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Giriraj Hospital

Investigators

  • Principal Investigator: Kirti S Pawar, MBBS,DA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2000

Study Completion

June 1, 2003

Study Registration Dates

First Submitted

June 5, 2006

First Submitted That Met QC Criteria

June 5, 2006

First Posted (Estimate)

June 6, 2006

Study Record Updates

Last Update Posted (Estimate)

June 6, 2006

Last Update Submitted That Met QC Criteria

June 5, 2006

Last Verified

May 1, 2000

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GRH/IERC/2000/12

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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