Scottish and Newcastle Anti-emetic Pre-treatment for Paracetamol Poisoning Study (SNAP)

NCT01050270 | Completed Phase 4 DMC

• 2 other identifiers: CZB/4/7222009-017800-10
• Study Type: interventional
• Target: 222
• Locations: 1 country
• Sites: 3

Brief 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). 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.

Conditions

Overdose

Outcome Measures

Primary Outcomes (1)

• 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.

  2 hours post start of treatment

Secondary Outcomes (1)

• The secondary endpoint is nausea or vomiting within 12h of initiation of acetylcysteine treatment.

  12 hours post start of treatment

Study Arms (4)

Ondansetron /acetylcysteine 20.25h

OTHER

Ondansetron followed by conventional acetylcysteine regimen

Drug: Ondansetron; Drug: acetylcysteine

Placebo/acetylcysteine 20.25h

OTHER

placebo followed by conventional acetylcysteine regimen

Drug: acetylcysteine

Ondansetron/acetylcysteine 12h

OTHER

ondansetron followed by modified acetylcysteine regimen

Drug: Ondansetron; Drug: acetylcysteine

Placebo/acetylcysteine 12h

OTHER

placebo followed by modified acetylcysteine regimen

Drug: acetylcysteine

Interventions

Ondansetron DRUG

4mgs iv bolus

Also known as: CAS number: 99614-02-5

Ondansetron /acetylcysteine 20.25h; Ondansetron/acetylcysteine 12h

acetylcysteine DRUG

100 mg/kg over 2 hours then 200mg/kg over 10 hours, followed by glucose 5% for 8 hours

Also known as: cas number: 616-91-1

Ondansetron/acetylcysteine 12h; Placebo/acetylcysteine 12h

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator
• Chief Scientist Office of the Scottish Government: collaborator

Study Sites (3)

Aberdeen Royal Infirmary

Aberdeen, AB25 2ZN, United Kingdom

Location

Royal Infirmary of Edinburgh

Edinburgh, EH16 4SA, United Kingdom

Location

Royal Victoria Infirmary

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 24290406 DERIVED

• Thanacoody 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.

  PMID: 23556549 DERIVED

MeSH Terms

Conditions

Drug Overdose

Interventions

Ondansetron; Acetylcysteine

Condition Hierarchy (Ancestors)

Prescription Drug Misuse; Drug Misuse; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Alasdair J Gray

  NHS Lothian

  PRINCIPAL INVESTIGATOR

• Harry K Thanacoody

  Newcastle Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• Jamie G Cooper

  NHS Grampian

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2010
• First Posted: January 15, 2010
• Study Start: September 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: March 1, 2013
• Last Updated: July 31, 2013

Record last verified: 2013-07

Locations

GB (3)