Condition category
Injury, Occupational Diseases, Poisoning
Date applied
15/11/2006
Date assigned
06/02/2007
Last edited
26/01/2009
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.sactrc.org

Contact information

Type

Scientific

Primary contact

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 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

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

Trial setting

Other

Trial 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

Phase

Phase II

Drug names

Fructose-1,6-Diphosphate

Primary outcome measures

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 trial start date

01/06/2006

Overall trial end date

01/06/2007

Reason abandoned

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

Patient

Age group

Adult

Gender

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

Trial 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

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

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

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes