OverdosePhase 4SNAPNCT01050270
Scottish and Newcastle Anti-emetic Pre-treatment for Paracetamol Poisoning Study (SNAP)
A Phase 4 study testing Ondansetron and acetylcysteine in people with Overdose, run by University of Edinburgh at 3 sites in United Kingdom.
Trial summary
This study is designed to assess the impact of new approaches to therapy for paracetamol poisoning. Standard therapy is currently acetylcysteine by intravenous infusion over 20.25h. This regimen is given to those deemed "at risk" using standard criteria (British National Formulary 200920). Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Overdose
- What is being tested?
- Ondansetron and acetylcysteine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 222 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Sep 2010to Mar 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Any patient admitted to hospital within 36 hours of a single acute paracetamol overdose; AND
- Requires treatment with acetylcysteine.
- These patients will include:
- Patients with no risk factors and timed paracetamol concentrations above the 200-line on the UK paracetamol overdose treatment nomogram.
- Patients with at least 1 risk factor and timed paracetamol concentrations above the 100-line on the UK paracetamol overdose treatment nomogram
- Patients presenting >8 hours, and at risk of liver damage based on history of dose ingested (BNF) that need immediate treatment
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- Risk factors are defined as follows:
- Nutritional deficiency, malnourished and/or debilitating disease: acute or chronic starvation, eating disorders, cachexia, malabsorption syndromes, AIDS, cystic fibrosis, hepatitis C, chronic alcoholism.
- Enzyme induction: use of drugs with this property (carbamazepine, rifampicin, barbiturates, phenytoin, rifabutin, efavirenz, nevirapine, St John's Wort; regular consumption of ethanol above advised amounts.
Who cannot join
- Patients:
- < 16 years old
- Detained under the Mental Health Act
- With known permanent cognitive impairment
- With a life-threatening illness
- Who are known to be pregnant
Show all 16Show fewer
- Who have previously participated in the study
- Unreliable history of paracetamol overdose
- Vomiting and requiring treatment antiemetic prior to randomisation
- Presenting after 36 hours of a single acute paracetamol overdose
- Presenting after taking a staggered paracetamol overdose (defined as when the overdose of paracetamol is taken over a period of more than 2 hours)
- Who take anticoagulants (e.g. warfarin) therapeutically or have taken an overdose of anticoagulants
- Who, in the opinion of the responsible clinician/nurse, are unlikely to complete the full course of acetylcysteine e.g. expressing wish to self-discharge
- Who in the opinion of the responsible clinician/nurse are unable to complete the initial questionnaire either themselves or with nurse assistance.
- Who have a history of hypersensitivity to 5HT3 antagonists
- Non-English speaking patients. (Trial information material will only be produced in English in view of the known and stable demographic of the Edinburgh and Newcastle self harm population)
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Aberdeen Royal Infirmary
Aberdeen, AB25 2ZN
Royal Infirmary of Edinburgh
Edinburgh, EH16 4SA
Royal Victoria Infirmary
Newcastle upon Tyne, NE1 4LP
About this study
Official title: A Randomised Trial to Assess the Effectiveness of Pre-treatment With Ondansetron at Reducing Nausea and Vomiting in Patients Treated With Either the Conventional Regimen or a Modified Regimen of Acetylcysteine for Paracetamol Poisoning
This study is designed to assess the impact of new approaches to therapy for paracetamol poisoning. Standard therapy is currently acetylcysteine by intravenous infusion over 20.25h. This regimen is given to those deemed "at risk" using standard criteria (British National Formulary 200920). It has 3 major problems, adverse events (nausea and vomiting and anaphylactoid reactions), therapy duration and complexity of administration.
This study is primarily designed to test the efficacy of prophylactic anti-emetic therapy.
It will also provide sufficient experience and data from a modified shortened IV acetylcysteine regimen to adequately design and power a study of the modified regimen as a new treatment for this common poison. Such an approach has a major potential to reduce patient adverse events from acetylcysteine therapy and shorten duration of hospital stay.
Read the detailed description
Paracetamol is the commonest poison seen in the United Kingdom and is present in approximately 40% of patients admitted with self harm. Current treatment involves use of the antidote acetylcysteine in patients deemed at risk of potential liver damage. This is given by intravenous infusion over a period of 20.25 hours. This regimen was designed in the 1970s and is empirical, in that a large loading dose of the antidote is administered followed by 2 decreasing concentrations. It is cumbersome to calculate and dilute within the ward and therefore subject to error in preparation. The initial infusion is associated with a significant rate of adverse reactions, in particular nausea and vomiting and anaphylactoid reactions. The latter are particularly troublesome and occur in up to 15% of patients treated. Therapy is discontinued and there is often confusion as to whether it can be restarted in a timely manner.
Studying antidotes in the management of poisoning is challenging not least because of the patient population and of the limited time available to make decisions and gain consent. This will be the first major clinical trial of antidote therapy in this poisoning in the UK in 30 years.
The final objective of this work is to develop a therapeutic regimen of acetylcysteine that does not cause such a high rate of adverse reactions and is also easier for nurses to make up.
The present study focuses on the potential use of ondansetron, an anti-emetic, prior to the administration of acetylcysteine. It will also allow preliminary data to be collected on a new approach to giving acetylcysteine using a modified 12 h regimen, which includes a slower initial intravenous infusion.
The primary trial outcome will therefore inform on the efficacy of ondansetron pre-treatment as an anti-emetic in this situation. In addition valuable data on the incidence of adverse effects caused by the modified acetylcysteine regimen, and changes in liver function and the inflammatory response to paracetamol liver injury caused by paracetamol within this modified acetylcysteine treatment will be obtained.
In addition an opportunity will be taken in a convenience sample of 40 patients to study the pharmacokinetics of acetylcysteine in this group using the standard and modified regimens.
A factorial design is being used to answer the key clinical questions. In total a maximum of 250 patients will be recruited and it is anticipated the data from 200 will be available for final analysis.
The demographic of this patient group is essentially Caucasian English-speaking and at this stage we do not propose to recruit non-English-speaking subjects.
- Conditions
- Overdose
- Being tested
- Ondansetron, acetylcysteine
- Medical subject headings
- Drug Overdose
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OndansetronDrug
Also called CAS number: 99614-02-5
4mgs iv bolus
acetylcysteineDrug
Also called cas number: 616-91-1
100 mg/kg over 2 hours then 200mg/kg over 10 hours, followed by glucose 5% for 8 hours
acetylcysteineDrug
Also called CAS number: 616-91-1
150 mg/kg over 15 mins 50 mg/kg over 4 hours 100 mg/kg over 16 hours
| Study group | Role | What they receive |
|---|---|---|
| Ondansetron /acetylcysteine 20.25h | Other | Ondansetron followed by conventional acetylcysteine regimen Receives: Drug: Ondansetron; Drug: acetylcysteine |
| Placebo/acetylcysteine 20.25h | Other | placebo followed by conventional acetylcysteine regimen Receives: Drug: acetylcysteine |
| Ondansetron/acetylcysteine 12h | Other | ondansetron followed by modified acetylcysteine regimen Receives: Drug: Ondansetron; Drug: acetylcysteine |
| Placebo/acetylcysteine 12h | Other | placebo followed by modified acetylcysteine regimen Receives: Drug: acetylcysteine |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint is the proportion of patients who do not vomit or retch within 2 hours of initiation of acetylcysteine treatment and no use of rescue medication. Retching will be defined as a vomit not producing any liquid.
Measured: 2 hours post start of treatment
Secondary outcomes (1)
The secondary endpoint is nausea or vomiting within 12h of initiation of acetylcysteine treatment.
Measured: 12 hours post start of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2010 (estimated)
- Study startSep 2010
- Primary completionDec 2012
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for OverdoseStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 222 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Lothian, Chief Scientist Office of the Scottish Government
- Responsible party
- Sponsor
- Investigators
- Alasdair J Gray, Principal investigator, NHS LothianHarry K Thanacoody, Principal investigator, Newcastle Hospitals NHS Foundation TrustJamie G Cooper, Principal investigator, NHS Grampian
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01050270
- Sponsor's protocol ID
- CZB/4/722
- Other IDs
- 2009-017800-10, 2009
- Acronym
- SNAP
- Status last verified
- Jul 2013
- First submitted
- 14 Jan 2010
- Last updated
- 31 Jul 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bateman DN, Dear JW, Thanacoody HK, Thomas SH, Eddleston M, Sandilands EA, Coyle J, Cooper JG, Rodriguez A, Butcher I, Lewis SC, Vliegenthart AD, Veiraiah A, Webb DJ, Gray A. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial. Lancet. 2014 Feb 22;383(9918):697-704. doi: 10.1016/S0140-6736(13)62062-0. Epub 2013 Nov 28.
PubMed 24290406Thanacoody HK, Gray A, Dear JW, Coyle J, Sandilands EA, Webb DJ, Lewis S, Eddleston M, Thomas SH, Bateman DN. Scottish and Newcastle antiemetic pre-treatment for paracetamol poisoning study (SNAP). BMC Pharmacol Toxicol. 2013 Apr 4;14:20. doi: 10.1186/2050-6511-14-20.
PubMed 23556549
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Trial to Assess the Effectiveness of Pre-treatment With Ondansetron at Reducing Nausea and Vomiting in Patients Treated With Either the Conventional Regimen or a Modified Regimen of Acetylcysteine for Paracetamol Poisoning
- ClinicalTrials.gov ID
- NCT01050270
- Acronym / sponsor ID
- SNAP / CZB/4/722
- Conditions
- Overdose
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 222 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- NHS Lothian, Chief Scientist Office of the Scottish Government
- Study start
- Sep 2010
- Primary completion
- Dec 2012 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 15 Jan 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to assess the impact of new approaches to therapy for paracetamol poisoning. Standard therapy is currently acetylcysteine by intravenous infusion over 20.25h. This regimen is given to those deemed "at risk" using standard criteria (British National Formulary 200920). It has 3 major problems, adverse events (nausea and vomiting and anaphylactoid reactions), therapy duration and complexity of administration.
This study is primarily designed to test the efficacy of prophylactic anti-emetic therapy.
It will also provide sufficient experience and data from a modified shortened IV acetylcysteine regimen to adequately design and power a study of the modified regimen as a new treatment for this common poison. Such an approach has a major potential to reduce patient adverse events from acetylcysteine therapy and shorten duration of hospital stay.
Detailed description
Paracetamol is the commonest poison seen in the United Kingdom and is present in approximately 40% of patients admitted with self harm. Current treatment involves use of the antidote acetylcysteine in patients deemed at risk of potential liver damage. This is given by intravenous infusion over a period of 20.25 hours. This regimen was designed in the 1970s and is empirical, in that a large loading dose of the antidote is administered followed by 2 decreasing concentrations. It is cumbersome to calculate and dilute within the ward and therefore subject to error in preparation. The initial infusion is associated with a significant rate of adverse reactions, in particular nausea and vomiting and anaphylactoid reactions. The latter are particularly troublesome and occur in up to 15% of patients treated. Therapy is discontinued and there is often confusion as to whether it can be restarted in a timely manner.
Studying antidotes in the management of poisoning is challenging not least because of the patient population and of the limited time available to make decisions and gain consent. This will be the first major clinical trial of antidote therapy in this poisoning in the UK in 30 years.
The final objective of this work is to develop a therapeutic regimen of acetylcysteine that does not cause such a high rate of adverse reactions and is also easier for nurses to make up.
The present study focuses on the potential use of ondansetron, an anti-emetic, prior to the administration of acetylcysteine. It will also allow preliminary data to be collected on a new approach to giving acetylcysteine using a modified 12 h regimen, which includes a slower initial intravenous infusion.
The primary trial outcome will therefore inform on the efficacy of ondansetron pre-treatment as an anti-emetic in this situation. In addition valuable data on the incidence of adverse effects caused by the modified acetylcysteine regimen, and changes in liver function and the inflammatory response to paracetamol liver injury caused by paracetamol within this modified acetylcysteine treatment will be obtained.
In addition an opportunity will be taken in a convenience sample of 40 patients to study the pharmacokinetics of acetylcysteine in this group using the standard and modified regimens.
A factorial design is being used to answer the key clinical questions. In total a maximum of 250 patients will be recruited and it is anticipated the data from 200 will be available for final analysis.
The demographic of this patient group is essentially Caucasian English-speaking and at this stage we do not propose to recruit non-English-speaking subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Ondansetron /acetylcysteine 20.25h | Other | Drug: Ondansetron, Drug: acetylcysteineOndansetron followed by conventional acetylcysteine regimen |
| Placebo/acetylcysteine 20.25h | Other | Drug: acetylcysteineplacebo followed by conventional acetylcysteine regimen |
| Ondansetron/acetylcysteine 12h | Other | Drug: Ondansetron, Drug: acetylcysteineondansetron followed by modified acetylcysteine regimen |
| Placebo/acetylcysteine 12h | Other | Drug: acetylcysteineplacebo followed by modified acetylcysteine regimen |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Any patient admitted to hospital within 36 hours of a single acute paracetamol overdose; AND
- Requires treatment with acetylcysteine.
- Patients with no risk factors and timed paracetamol concentrations above the 200-line on the UK paracetamol overdose treatment nomogram.
- Patients with at least 1 risk factor and timed paracetamol concentrations above the 100-line on the UK paracetamol overdose treatment nomogram
- Patients presenting >8 hours, and at risk of liver damage based on history of dose ingested (BNF) that need immediate treatment
Key exclusion criteria (16 listed)
- < 16 years old
- Detained under the Mental Health Act
- With known permanent cognitive impairment
- With a life-threatening illness
- Who are known to be pregnant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OndansetronAlso: CAS number: 99614-02-54mgs iv bolus | Drug | Ondansetron /acetylcysteine 20.25h, Ondansetron/acetylcysteine 12h |
| acetylcysteineAlso: cas number: 616-91-1100 mg/kg over 2 hours then 200mg/kg over 10 hours, followed by glucose 5% for 8 hours | Drug | Ondansetron/acetylcysteine 12h, Placebo/acetylcysteine 12h |
| acetylcysteineAlso: CAS number: 616-91-1150 mg/kg over 15 mins 50 mg/kg over 4 hours 100 mg/kg over 16 hours | Drug | Ondansetron /acetylcysteine 20.25h, Placebo/acetylcysteine 20.25h |
Primary outcome
The primary endpoint is the proportion of patients who do not vomit or retch within 2 hours of initiation of acetylcysteine treatment and no use of rescue medication. Retching will be defined as a vomit not producing any liquid.
Time frame: 2 hours post start of treatment
1 secondary outcome
The secondary endpoint is nausea or vomiting within 12h of initiation of acetylcysteine treatment.
Time frame: 12 hours post start of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2013.
- Derived from this study: PubMed 24290406Bateman DN, Dear JW, Thanacoody HK, Thomas SH, Eddleston M, Sandilands EA, Coyle J, Cooper JG, Rodriguez A, Butcher I, Lewis SC, Vliegenthart AD, Veiraiah A, Webb DJ, Gray A. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial. Lancet. 2014 Feb 22;383(9918):697-704. doi: 10.1016/S0140-6736(13)62062-0. Epub 2013 Nov 28.
- Derived from this study: PubMed 23556549Thanacoody HK, Gray A, Dear JW, Coyle J, Sandilands EA, Webb DJ, Lewis S, Eddleston M, Thomas SH, Bateman DN. Scottish and Newcastle antiemetic pre-treatment for paracetamol poisoning study (SNAP). BMC Pharmacol Toxicol. 2013 Apr 4;14:20. doi: 10.1186/2050-6511-14-20.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alasdair J Gray principal investigator
NHS Lothian
Harry K Thanacoody principal investigator
Newcastle Hospitals NHS Foundation Trust
Jamie G Cooper principal investigator
NHS Grampian
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ondansetron and acetylcysteine in people with Overdose, run by University of Edinburgh at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary endpoint is the proportion of patients who do not vomit or retch within 2 hours of initiation of acetylcysteine treatment and no use of rescue medication. Retching will be defined as a vomit not producing any liquid. (time frame: 2 hours post start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01050270, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2013.