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
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