Fructose-1,6-diphosphate (FDP) in yellow oleander poisoning

ISRCTN	ISRCTN80882762
DOI	https://doi.org/10.1186/ISRCTN80882762
Secondary identifying numbers	071669; sactrc0305

Submission date: 15/11/2006
Registration date: 06/02/2007
Last edited: 26/01/2009

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Injury, Occupational Diseases, Poisoning

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English Summary

Not provided at time of registration

Study website

Contact information

Prof Andrew Dawson
Scientific

South Asian Clinical Toxicology Research Collaboration (SACTRC)
Department of Medicine
University of Peradeniya
Peradeniya
20000
Sri Lanka

Phone	+94 (0)81 4479822
Email	adawson@sactrc.org

Study information

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
Scientific title	Phase II randomised controlled trial of fructose-1,6-diphosphate (FDP) in yellow oleander poisoning
Study 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.
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

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	32
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 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

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

c/o Andrew Dawson
Department of Medicine
University of Peradeniya
Peradeniya
20000
Sri Lanka

Phone	+94 (0)81 4479822
Email	adawson@sactrc.org
Website	http://www.sactrc.org
"ROR"	https://ror.org/04z435g27

Funders

Funder type

Charity

International collaborative research grant:

No information available

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

No information available

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

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan