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

ISRCTN	ISRCTN37500282
DOI	https://doi.org/10.1186/ISRCTN37500282
Protocol serial number	BLT-Dylo-07/01
Sponsor	Barts and The London NHS Trust (UK)
Funder	Javelin Pharmaceuticals UK Limited (UK)

Submission date: 23/12/2008
Registration date: 12/02/2009
Last edited: 09/06/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Surgery

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Nilesh Randive
Scientific

PARC
Unit 11, First Floor Dominion House
59 Bartholomew Close
West Smithfield
London
EC1A 7BE
United Kingdom

Email	drnilran@gmail.com

Study information

Primary study design	Interventional
Study design	Prospective open-label randomised single-centre phase IV study
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	The cerebrospinal fluid (CSF) pharmacokinetics of a single pre-operative intravenous bolus dose of diclofenac (Dyloject®) in comparison to diclofenac infusion (Voltarol®): a prospective open-label randomised single-centre phase IV study
Study objectives	Dyloject®, a novel injectable diclofenac bolus is ideally suited for peri-operative anti-inflammatory analgesic use, and in view of the high peak plasma concentration following rapid intravenous administration may facilitate greater penetration of the central nervous system (CNS) and hence exert additional beneficial central actions.
Ethics approval(s)	South East Regional Ethics Committee approval decision awaiting as of 14th January 2009
Health condition(s) or problem(s) studied	Peri-operative anti-inflammatory analgesia
Intervention	Dyloject® (75 mg) single intravenous bolus or Voltarol® ampoules (75 mg) single intravenous infusion will be given pre-operatively prior to spinal anaesthesia for surgery and cerebrospinal fluid sampling.
Intervention type	Drug
Phase	Phase IV
Drug / device / biological / vaccine name(s)	Diclofenac (Dyloject®, Voltarol®)
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	1. Characterise CSF PGE2 levels in the normal uninjured human with or without diclofenac 2. Establish baseline CSF and plasma prostaglandins and cytokine levels 3. Examine the relationship between CNS and plasma PGE2 levels 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.
Completion date	05/08/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	20
Key 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
Key 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
Date of first enrolment	05/02/2009
Date of final enrolment	05/08/2010

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

PARC

London
EC1A 7BE
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

09/06/2016: No publications found, verifying study status with principal investigator.