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

ISRCTN	ISRCTN55264358
DOI	https://doi.org/10.1186/ISRCTN55264358
Secondary identifying numbers	GR063560

Submission date: 29/07/2002
Registration date: 29/07/2002
Last edited: 17/02/2015

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Injury, Occupational Diseases, Poisoning

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Mr Michael Eddleston
Scientific

Scottish Poisons Information Bureau
Royal Infirmary
51 Little France Crescent
Edinburgh
EH16 4SA
United Kingdom

Phone	+44 (0)131 242 1383
Email	eddlestonm@yahoo.com

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	Acute organophosphate pesticide poisoning in Sri Lanka: management, complications and pharmacogenetics
Study objectives	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(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Acute organophosphate self-poisoning
Intervention	Atropine and pralidoxime chloride (2 g stat followed by 500 mg/h for up to seven days) versus atropine and saline placebo.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	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 study start date	01/05/2004
Completion date	01/07/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	1500
Key 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.
Key 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
Date of first enrolment	01/05/2004
Date of final enrolment	01/05/2007

Locations

Countries of recruitment

Scotland
Sri Lanka
United Kingdom

Study participating centre

Scottish Poisons Information Bureau

Edinburgh
EH16 4SA
United Kingdom

Sponsor information

University of Oxford (UK)
University/education

University Offices
Wellington Square
Oxford
OX1 2JD
England
United Kingdom

Phone	+44 (0)1865 270000
Email	Research.services@admin.ox.ac.uk
Website	http://www.ox.ac.uk/
"ROR"	https://ror.org/052gg0110

Funders

Funder type

Charity

Wellcome Trust
Private sector organisation / International organizations

Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	30/06/2009		Yes	No