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

• Register: ISRCTN
• Last refreshed on: 13 January 2015
• Main ID: ISRCTN80882762
• Date of registration: 06/02/2007
• Prospective Registration: No
• Primary sponsor: South Asian Clinical Toxicology Research Collaboration (SACTRC) (Sri Lanka)
• Public title: Fructose-1,6-diphosphate (FDP) in yellow oleander poisoning
• Scientific title: Phase II randomised controlled trial of fructose-1,6-diphosphate (FDP) in yellow oleander poisoning
• Date of first enrolment: 01/06/2006
• Target sample size: 32
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN80882762
• Study type: Interventional
• Study design: Placebo controlled, randomised phase II study (Treatment)

Countries of recruitment

Sri Lanka

Contacts

• Name: Andrew Dawson

Key inclusion & exclusion criteria

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.
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)

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Yellow oleander-induced cardiac toxicity
Injury, Occupational Diseases, Poisoning
Cardiac toxicity

Intervention(s)

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.

Primary Outcome(s)

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(s)

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).

Secondary ID(s)

071669; sactrc0305

Source(s) of Monetary Support

International collaborative research grant:, The Wellcome Trust (UK) (grant ref: 071669), The National Health and Medical Research Council (NHMRC) of Australia (Australia)