The cerebrospinal fluid (CSF) pharmacokinetics of a single pre-operative intravenous bolus dose of diclofenac (Dyloject®) in comparison to diclofenac infusion (Voltarol®)

Phase 4

Completed

• Conditions: Peri-operative anti-inflammatory analgesia; Surgery; Peri-operative analgesia

• Registration Number: ISRCTN37500282
• Lead Sponsor: Barts and The London NHS Trust (UK)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-02-12
• Last Update Posted: 17 October 2016

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Male or female patients aged at least 18 years
2. Scheduled to undergo surgery performed under spinal anaesthesia
3. Patients must be inpatients
4. Patient has given written informed consent

Exclusion Criteria

1. History of bleeding diathesis or use of anticoagulant or antiplatelet agent
2. History of spinal or neurological disease (including raised intracranial pressure), or surgery contraindicating spinal anaesthesia
3. Use of aspirin within 72 hours prior to surgery
4. Use of other non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol or steroids within 12 hours before surgery
5. Hypersensitivity to diclofenac or local anaesthetics
6. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) or blood urea nitrogen (BUN) greater than 1.5 x the upper limit of the reference range, or creatinine greater than the upper limit of the reference range
7. Any other abnormal laboratory results considered clinically significant in relation to this study by the investigator
8. Presence of oliguria, anaemia, hypotension or hypovolaemia
9. Contraindications to NSAID/diclofenac
10. Patients who are unwilling or unable to conform to the protocol
11. Patients who have received an unlicensed drug less than 30 days prior to the study
12. Patients who have been previously admitted to the study
13. Pregnant or lactating females or females of child-bearing potential who are unwilling to undertake a pregnancy test (urinary beta-human chorionic gonadotropin [B-HCG])
14. A bloody tap (visible blood in CSF)
15. Patients with a hypersensitivity to the excipients hydroxypropylbetadex (HPßCD) or monothioglycerol
16. Operations with high risk of haemorrhage
17. Patients who are considered unsuitable by the responsible anaesthetist - for whom spinal anaesthesia is deemed to constitute an unacceptable, increased risk
18. Patients who are involved in existing research

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Characterisation of the CSF diclofenac kinetics following administration of intravenous Dyloject®. The patients will receive the drug at 65, 35 and 5 minutes prior to CSF sampling.

Secondary Outcome Measures

Name	Time	Method
1. Characterise CSF PGE2 levels in the normal uninjured human with or without diclofenac<br>2. Establish baseline CSF and plasma prostaglandins and cytokine levels<br>3. Examine the relationship between CNS and plasma PGE2 levels<br>4. Establish proof of concept for further analyses: an optional continuation of this pilot study is proposed dependant on interim analysis of the first phase. This would entail a further 18 patients entering the study.