Contact information
Type
Scientific
Primary contact
Mr Michael Eddleston
ORCID ID
Contact details
Scottish Poisons Information Bureau
Royal Infirmary
51 Little France Crescent
Edinburgh
EH16 4SA
United Kingdom
+44 (0)131 242 1383
eddlestonm@yahoo.com
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
GR063560
Study information
Scientific title
Acute organophosphate pesticide poisoning in Sri Lanka: management, complications and pharmacogenetics
Acronym
Study hypothesis
We propose to carry out a randomised controlled trial of single or multi-dose activated charcoal regimens in Sri Lankan patients presenting with a history of acute poisoning. The study will look at unselected adult patients with most forms of acute poisoning.
The main hypothesis is that the multi-dose activated charcoal regimen will reduce the case fatality rate from 10% to 7%, hence the first principal comparison will be multi-dose activated charcoal versus no intervention. The potential of multidose regimens to work long after ingestion - due to interruption of enterohepatic circulation and gut dialysis - means that such a regimen is more likely to work in a situation where people typically present several hours after ingestion.
We suspect that a single dose will be less effective since most absorption will have taken place by the patient's presentation to hospital. Therefore, the second principal comparison will test the hypothesis that the case fatality rate in patients receiving a single dose of activated charcoal is equal to that in patients receiving multiple doses.
In order to investigate whether a single dose of activated charcoal has a similar effect as giving no intervention, the third principal comparison will test the hypothesis that the case fatality rate in patients receiving a single dose of activated charcoal is equal to that in patients receiving no intervention.
It is possible that both treatment regimens, if effective in reducing case fatality rates, will be more effective the earlier they are started. Therefore we will assess the trends in clinical effectiveness according to time post-ingestion to start of therapy.
In order to determine whether treatment should be started irrespective of severity, we will also assess trends in case fatality rates across a gradient of severity.
Admission blood samples will be retrospectively analysed to determine the identity of the poison ingested. The primary analyses will then be repeated with correction for the identity of the poison.
Subgroup analyses are planned to look at the consistency of treatment effect across different types of poison i.e. dimethylated and diethylated Organophosphate (OP) pesticides, organochlorines, all pesticides, and yellow oleander. These will be carried out for the primary outcome and secondary outcomes, plus trends with time and severity.
Please note that this RCT has a nested study registered under ISRCTN55264358. For more details on this nested study please visit http://www.isrctn.com/ISRCTN55264358.
The overall trial end date has been extended from 31/10/2004 to 01/12/2004.
Ethics approval
Not provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Acute self-poisoning in the developing world
Intervention
No charcoal, single 50 g dose of superactivated charcoal, multiple doses (6 x every four hour doses of superactivated charcoal).
Intervention type
Drug
Phase
Not Applicable
Drug names
Activated charcoal
Primary outcome measures
All-cause mortality at hospital discharge.
Secondary outcome measures
Organophosphate pesticides:
1. Percentage of patients requiring intubation
2. Period of 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)
Organochlorine pesticides:
Incidence of status epilepticus (continuous overt generalised seizure activity for mroe than five minutes or two generalised seizures without an intervening recovery of consciousness)
Yellow oleander:
1. Cardiac dysrhythmias requiring anti-digoxin Fab (3° heart block, Mobitz type II 2° block, sinus bradycardia with heart rate less than 35 bpm, and sinus arrest or block with sinus pauses more than 3 seconds), or
2. Serum potassium greater than 6.0
Overall trial start date
31/03/2002
Overall trial end date
01/12/2004
Reason abandoned
Eligibility
Participant inclusion criteria
All patients presenting with a history of acute self-poisoning in selected Sri Lankan hospitals
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
4650
Participant exclusion criteria
We hope to recruit all patients admitted to the medical wards with a history of acute poisoning, except for those:
1. Under the age of 14 years
2. Known to be pregnant
3. Who have ingested hydrocarbons alone or corrosives (good prognosis for former, charcoal contraindicated for latter)
4. Who require oral medication
5. Who present more than 72 hours post-ingestion
6. Patients under the age of 16 or unconscious, who are present without relatives
Recruitment start date
31/03/2002
Recruitment end date
16/10/2004
Locations
Countries of recruitment
Sri Lanka
Trial participating centre
Scottish Poisons Information Bureau
Edinburgh
EH16 4SA
United Kingdom
Sponsor information
Organisation
University of Oxford (UK)
Sponsor details
University Offices
Wellington Square
Oxford
OX1 2JD
United Kingdom
+44 (0)1865 270000
Research.services@admin.ox.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Wellcome Trust
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
international
Location
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
Results - basic reporting
Publication summary
1. 2007 study protocol: http://www.ncbi.nlm.nih.gov/pubmed/17498281
2. 2008 results: http://www.ncbi.nlm.nih.gov/pubmed/18280328
Publication citations
-
Study protocol
Eddleston M, Juszczak E, Buckley NA, Senarathna L, Mohammed F, Allen S, Dissanayake W, Hittarage A, Azher S, Jeganathan K, Jayamanne S, Sheriff MH, Warrell DA, , Study protocol: a randomised controlled trial of multiple and single dose activated charcoal for acute self-poisoning., BMC Emerg Med, 2007, 7, 2, doi: 10.1186/1471-227X-7-2.
-
Results
Eddleston M, Juszczak E, Buckley NA, Senarathna L, Mohamed F, Dissanayake W, Hittarage A, Azher S, Jeganathan K, Jayamanne S, Sheriff MR, Warrell DA, , Multiple-dose activated charcoal in acute self-poisoning: a randomised controlled trial., Lancet, 2008, 371, 9612, 579-587, doi: 10.1016/S0140-6736(08)60270-6.