Condition category
Injury, Occupational Diseases, Poisoning
Date applied
23/01/2009
Date assigned
28/01/2009
Last edited
28/01/2009
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

Prof Andrew Dawson

ORCID ID

Contact details

Program Director
Visiting Professor of Medicine
South Asian Clinical Toxicology Research Collaboration (SACTRC)
University of Peradeniya
Peradeniya
20400
Sri Lanka
+94 (0)81 447 9822
adawson@sactrc.org

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

A dose-finding phase II study of diazepam in adult patients presenting with signs or symptoms of acute organophosphate poisoning

Acronym

Study hypothesis

What is the safe and effective diazepam regimen in organophosphate (OP) poisoning that could:
1. Reduce mortality and/or the need for ventilation
2. Provide moderate sedation
3. Not cause symptomatic adverse effects on blood pressure

Ethics approval

1. Sri Lanka Medical Association Ethical Committee gave approval on the 13th January 2006 (ref: 05-023)
2. University of Peradeniya, Faculty of Medicine, Ethical Review Committee gave approval on the 16th November 2007 (ref: 2006/EC/40)
3. Australian Nation University Ethics Committee gave approval on 15th February 2006 (ref: 2005/354)

Study design

Dose escalation phase II randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Organophosphate poisoning

Intervention

The dose escalation relates to a course of diazepam. The first three doses are single doses of 2.5 mg, 5 mg, and 10 mg. The fourth group will receive a dose of 10 mg - and then two subsequent doses of 5 mg at 6 hour intervals. The first cohort of patients (2 controls and 6 diazepam) would receive a loading dose of 2.5 mg. If this is tolerated the next cohort would receive the next highest loading dose (i.e. 5 mg) and so on. If any patients do not tolerate a dose then the trial will be terminated at that dose level. Diazepam would be administered by a slow infusion with the total dose being given over 30 minutes. The study will be nested into observational trials being conducted in the same hospitals.

This standard treatment is determined by the attending physician who maintains clinical responsibility for all patients. While there may be some minor variation between hospitals current care consists of patient resuscitation, gastrointestinal decontamination when indicated, atropinisation and the use of pralidoxime (typically one gram every six hours). All treatment is recorded by the research team. This intervention represents an added treatment to the existing standard of care.

Intervention type

Drug

Phase

Phase II

Drug names

Diazepam

Primary outcome measures

Number of patients that exhibit possible adverse effects such as:
1. A decrease in level of consciousness (measured using the Glasgow Coma Scale)
2. Respiratory depression (measured by a respiratory rate less than 10, and a tidal volume of less than 180 ml/breath using a Wright's spirometer)
3. Hypotension (blood pressure [BP] less than 90/60 mmHg, or a drop of greater than 20 mmHg systolic in a normotensive patient, i.e. systolic BP less than 140 mmHg)

Monitored every 15 minutes for the first 2 hours of administration of diazepam or placebo and then monitored hourly for the next 3 hours, and thereafter 4-hourly if the patient is clinically well, or more frequently if there are any clinical concerns.

Secondary outcome measures

1. Number of patients that required ventilation
2. Changes in electroencephalogram (EEG), arterial blood gas (ABG), tidal volume and capnography
3. Patients who had seizures or died
Monitored at baseline, 1 hour, 12 hours, 24 hours and daily. Continuous capnographic recording shall also be performed.

Overall trial start date

01/11/2008

Overall trial end date

09/06/2009

Reason abandoned

Eligibility

Participant inclusion criteria

Patients (aged 16 to 60 years, either sex) with symptomatic acute OP poisoning

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

32

Participant exclusion criteria

1. Patients who do not consent
2. Aged less than 16 years or greater than 60 years
3. Pregnant women and lactating mothers
4. Unavailability of ventilator
5. Patients in whom endotracheal (ET) intubation is likely to be difficult
6. Have a Glasgow Coma Score (GCS) less than 12 at the time of recruitment
7. Ingested benzodiazepines in addition to OP
8. Have established renal or hepatic failure
9. Have indications for therapeutic diazepam
10. Patients who have respiratory failure requiring ventilatory support
11. Patients who have systolic blood pressure of less than 90 mmHg within 2 hours of administration of diazepam

Recruitment start date

01/11/2008

Recruitment end date

09/06/2009

Locations

Countries of recruitment

Sri Lanka

Trial participating centre

Program Director, Visiting Professor of Medicine
Peradeniya
20400
Sri Lanka

Sponsor information

Organisation

South Asian Clinical Toxicology Research Collaboration (SACTRC) (Sri Lanka)

Sponsor details

c/o Professor Andrew Hamilton Dawson
Program Director
Visiting Professor of Medicine
University of Peradeniya
Peradeniya
20400
Sri Lanka
+94 (0)81 447 9822
adawson@sactrc.org

Sponsor type

Research organisation

Website

http://www.sactrc.org

Funders

Funder type

Charity

Funder name

International Collaborative Research Grant:

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

The Wellcome Trust (UK) (grant ref: 071669)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

National Health and Medical Research Council (NHMRC) (Australia)

Alternative name(s)

NHMRC

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Australia

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

Publication citations

Additional files

Editorial Notes