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

This study has been completed.
Sponsor:
Information provided by:
Giriraj Hospital
ClinicalTrials.gov Identifier:
NCT00333944
First received: June 5, 2006
Last updated: NA
Last verified: May 2000
History: No changes posted
  Purpose

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 Intervention
Acute Organophosphorus Pesticide Poisoning
Drug: Pralidoxime(drug)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effectiveness of High Dose Pralidoxime in the Treatment of Organophosphorus Pesticide Poisoning – a Randomised Controlled Trial

Resource links provided by NLM:


Further study details as provided by Giriraj Hospital:

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

Estimated Enrollment: 200
Study Start Date: May 2000
Estimated Study Completion Date: June 2003
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.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00333944

Locations
India
Giriraj Hospital and Intensive Care Unit.
Baramati. Pune District., Maharashtra., India, 413 102.
Sponsors and Collaborators
Giriraj Hospital
Investigators
Principal Investigator: Kirti S Pawar, MBBS,DA
  More Information

No publications provided by Giriraj Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00333944     History of Changes
Other Study ID Numbers: GRH/IERC/2000/12
Study First Received: June 5, 2006
Last Updated: June 5, 2006
Health Authority: India: Indian Council of Medical Research

Keywords provided by Giriraj Hospital:
Organophosphorus poisoning
Atropine
Pralidoxime
Intermediate syndrome.

Additional relevant MeSH terms:
Poisoning
Substance-Related Disorders
Pralidoxime
Antidotes
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cholinesterase Reactivators
Enzyme Reactivators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on April 17, 2014