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

NCT ID: NCT00333944

Last Updated: 2006-06-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-05-31
• Study Completion Date: 2003-06-30

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.

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.

Conditions

Acute Organophosphorus Pesticide Poisoning

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Pralidoxime(drug)

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Giriraj Hospital

OTHER

Sponsor Role: lead

Principal Investigators

Kirti S Pawar, MBBS,DA

Role: PRINCIPAL_INVESTIGATOR

Locations

Giriraj Hospital and Intensive Care Unit.

Baramati. Pune District., Maharashtra, India

Countries

India

References

Pawar KS, Bhoite RR, Pillay CP, Chavan SC, Malshikare DS, Garad SG. Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial. Lancet. 2006 Dec 16;368(9553):2136-41. doi: 10.1016/S0140-6736(06)69862-0.

Reference Type: DERIVED

PMID: 17174705 (View on PubMed)

Other Identifiers

GRH/IERC/2000/12

Identifier Type: -

Identifier Source: org_study_id