Condition category
Injury, Occupational Diseases, Poisoning
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Mr Michael Eddleston


Contact details

Scottish Poisons Information Bureau
Royal Infirmary
51 Little France Crescent
EH16 4SA
United Kingdom
+44 (0)131 242 1383

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Acute organophosphate pesticide poisoning in Sri Lanka: management, complications and pharmacogenetics


Study hypothesis

We propose to carry out a double-blind randomised controlled trial (RCT) of pralidoxime in adult patients presenting with a history and symptoms of organophosphate (OP) poisoning. Primary outcome will be in-hospital mortality; secondary outcomes will include the occurrence of serious complications (respiratory arrest, intermediate syndrome) and time requiring assisted ventilation. Analysis will be on an intention-to-treat basis; the effects of reported time to treatment after poisoning and status on admission will also be assessed.

This RCT will be nested into a study of activated charcoal in unselected cases of poisoning (ISRCTN02920054). All investigations and outcome assessments for ISRCTN02920054 will suffice for this RCT. Extra blood samples will not be taken from patients in this RCT.

The main hypothesis is that the pralidoxime will reduce the case fatality rate from 25% to 19%, hence the primary comparison will be pralidoxime versus placebo. The dimethyl versus diethyl state of the OPs is thought to be fundamental for the effectiveness of oximes in OP poisoning. Dimethylated acetylcholinesterase ages quickly such that oximes do not work in vitro more than 12 hours post-ingestion; in contrast, diethylated acetylcholinesterase age slower so that oximes in vitro work for three to four days post-ingestion. Therefore, once the dimethyl/diethyl status has been retrospectively determined, the analysis will be repeated separating the two groups of OP agents.

It is possible that the oxime, if effective in reducing case fatality rates, will be more effective the earlier it is started. Therefore we will assess the trends in clinical effectiveness according to time post-ingestion to start of therapy. This will be repeated once dimethyl compounds have been distinguished from diethyl compounds. We also want to determine whether treatment should be started irrespective of severity. We will therefore assess trends in case fatality rates across a gradient of severity.

We hypothesise that pralidoxime treatment will prevent the occurrence of the intermediate syndrome; this will therefore be an important secondary outcome. This analysis will be repeated once retrospective toxicological analysis has separated dimethyl compounds from diethyl compounds.

Subgroup analyses are planned to look at the consistency of treatment effect across different types of pesticide, i.e. dimethylated versus diethylated OP pesticides, and for locally common pesticides. A further subgroup analysis will be performed according to the presence of reactivatable acetylcholinesterase before treatment, following retrospective assays of ex-vivo reactivatability.

On 14/12/2007 the overall trial end date was changed from 31/05/2007 to 01/07/2007.

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet


Acute organophosphate self-poisoning


Atropine and pralidoxime chloride (2 g stat followed by 500 mg/h for up to seven days) versus atropine and saline placebo.

Intervention type



Not Applicable

Drug names

Atropine, pralidoxime chloride

Primary outcome measure

All-cause mortality at hospital discharge

Secondary outcome measures

1. Percentage of patients requiring intubation
2. Time requiring ventilation
3. Percentage of patients developing the intermediate syndrome (cranial nerve palsies and/or proximal weakness, without distal weakness, after resolution of the cholinergic crisis)

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

All patients (aged 14 years of above, either sex) presenting with history and signs of acute organophosphate self-poisoning in selected Sri Lankan hospitals, requiring atropine.

Participant type


Age group




Target number of participants


Participant exclusion criteria

We hope to recruit all patients admitted to the medical wards with a history of acute poisoning and symptoms and signs of organophosphate poisoning, except for those:
1. Under the age of 14 years
2. Known to be pregnant
3. Have previously received Pralidoxime
4. Patients under the age of 16 or unconscious, who are present without relatives

Recruitment start date


Recruitment end date



Countries of recruitment

Sri Lanka

Trial participating centre

Scottish Poisons Information Bureau
EH16 4SA
United Kingdom

Sponsor information


University of Oxford (UK)

Sponsor details

University Offices
Wellington Square
United Kingdom
+44 (0)1865 270000

Sponsor type




Funder type


Funder name

Wellcome Trust

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

International organizations


United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

2009 results in

Publication citations

  1. Results

    Eddleston M, Eyer P, Worek F, Juszczak E, Alder N, Mohamed F, Senarathna L, Hittarage A, Azher S, Jeganathan K, Jayamanne S, von Meyer L, Dawson AH, Sheriff MH, Buckley NA, Pralidoxime in acute organophosphorus insecticide poisoning--a randomised controlled trial., PLoS Med., 2009, 6, 6, e1000104, doi: 10.1371/journal.pmed.1000104.

Additional files

Editorial Notes