Contact information
Type
Scientific
Contact name
Prof Andrew Dawson
ORCID ID
Contact details
South Asian Clinical Toxicology Research Collaboration (SACTRC)
Department of Medicine
University of Peradeniya
Peradeniya
20000
Sri Lanka
+94 (0)81 4479822
adawson@sactrc.org
Additional identifiers
EudraCT/CTIS number
IRAS number
ClinicalTrials.gov number
Protocol/serial number
071669; sactrc0305
Study information
Scientific title
Phase II randomised controlled trial of fructose-1,6-diphosphate (FDP) in yellow oleander poisoning
Acronym
FDP Oleander Toxicity
Study hypothesis
Fructose-1,6-diphosphate (FDP) can reverse yellow oleander-induced cardiac toxicity in humans, specifically cardiac arrhythmia and hyperkalaemia.
Ethics approval(s)
1. Australian National University Human Ethics Research Committee (Approval 2005/208) on 16th September 2005.
2. Sri Lankan Medical Association Ethical Review Committee (Approval ERC/O5-004) on 20th July 2005.
Study design
Placebo controlled, randomised phase II study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
Other
Study type
Treatment
Patient information sheet
Condition
Yellow oleander-induced cardiac toxicity
Intervention
A blood sample will be taken on all randomised patients at the start and end of the infusion and 30 minutes, four and 12 hours later and then at daily intervals. Serum potassium, magnesium, calcium, as well as renal function and liver function will be measured (routine clinical biochemistry methodology). The cardiac glycoside and FDP concentration will also be measured at these times.
Four dose levels of FDP will be studied with the dose doubled if the results in the preceding eight patients do not indicate any concerning dose-related adverse effects. Two patients will receive a placebo and six patients will receive active treatment at each dose level.
Doses:
The first dose will be 30 mg/kg, 60% of the dose shown to be effective for this indication in dogs (50 mg/kg Intravenous [IV]). The dose will be doubled (60 mg/kg, 125 mg/kg) until 250 mg/kg assuming there is no significant toxicity attributed to the preparation at the previous dose. All these doses are well within the range of doses used in previous human studies. The highest dose is chosen as it was the most effective IV dose in one human study of ischemia/reperfusion injury post cardiac surgery (although FDP was also used in the cardioplegia solution), and larger doses (three doses of 250 mg/kg) seemed no more effective in this study and a non-significantly higher rate of acidosis and atrial fibrillation was also observed. Doses will be diluted in 5% dextrose and infused over 30 minutes with infusion pumps. Placebo infusions will be an equal volume of 5% dextrose. Drugs will be prepared shortly before use by a registered pharmacist. Treating doctors will be blind to treatment allocation.
Intervention type
Drug
Pharmaceutical study type(s)
Phase
Phase II
Drug/device/biological/vaccine name(s)
Fructose-1,6-Diphosphate
Primary outcome measure
The primary outcome will be the time to revert to continuous sinus rhythm with rate more than 44/min, in those receiving FDP versus the placebo group.
Secondary outcome measures
1. The number of patients with sinus rhythm with rate more than 44 bpm at two hours
2. Number of patients administered DigiFab
3. Other adverse events
4. Death
Secondary analysis will also compare the results at each dosing level as well as comparing trends with dose. Adverse events reported by doctors will be rated by them as to the likelihood of them being due to FDP infusion (certain, probable, possible, unlikely).
Overall study start date
01/06/2006
Overall study end date
01/06/2007
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Patients (16 years of age and older, male or female) with significant cardiotoxicity will be recruited to this study, i.e. those with: 3° heart block, Mobitz type II 2° block, atrial tachyarrhythmias, sinus bradycardia with heart rate less than 35 bpm, or sinus arrest or block with sinus pauses more than 3 seconds.
Participant type(s)
Patient
Age group
Adult
Sex
Both
Target number of participants
32
Participant exclusion criteria
1. No consent
2. Pregnant
3. Less than 16 years of age
4. Ingested other cardioactive substances in addition to oleander
5. Other major medical conditions (e.g. cardiovascular disease renal or hepatic failure)
Recruitment start date
01/06/2006
Recruitment end date
01/06/2007
Locations
Countries of recruitment
Sri Lanka
Study participating centre
South Asian Clinical Toxicology Research Collaboration (SACTRC)
Peradeniya
20000
Sri Lanka
Sponsor information
Organisation
South Asian Clinical Toxicology Research Collaboration (SACTRC) (Sri Lanka)
Sponsor details
c/o Andrew Dawson
Department of Medicine
University of Peradeniya
Peradeniya
20000
Sri Lanka
+94 (0)81 4479822
adawson@sactrc.org
Sponsor type
Research organisation
Website
ROR
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
The National Health and Medical Research Council (NHMRC) of Australia (Australia)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Individual participant data (IPD) sharing plan
IPD sharing plan summary
Not provided at time of registration
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|