Condition category
Injury, Occupational Diseases, Poisoning
Date applied
29/07/2002
Date assigned
29/07/2002
Last edited
17/02/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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

http://www.ox.ac.uk/

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

  1. 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.

  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.

Additional files

Editorial Notes