Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000648123
Ethics application status
Approved
Date submitted
18/04/2019
Date registered
1/05/2019
Date last updated
5/11/2021
Date data sharing statement initially provided
1/05/2019
Date results information initially provided
29/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Lignocaine versus Opioids in Coronary Intervention: Assessing Antiplatelet Activity and Ticagrelor Levels (LOCAL) study
Scientific title
Lignocaine versus opioids as analgesia in patients undergoing percutaneous coronary intervention and its pharmacokinetic and pharmacodynamic impacts on the antiplatelet activity of ticagrelor
Secondary ID [1] 297889 0
Nil known
Universal Trial Number (UTN)
U1111-1231-1375
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
coronary artery disease 312265 0
Analgesia 312266 0
Percutaneous coronary intervention 312267 0
Condition category
Condition code
Anaesthesiology 310814 310814 0 0
Pain management
Cardiovascular 310815 310815 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomised controlled trial comparing intravenous lignocaine to intravenous fentanyl in patients requiring periprocedural analgesia for percutaneous coronary intervention to evaluate pharmacokinetic and pharmacodynamic impact on ticagrelor. The angiogram and coronary stent insertion procedure typically lasts 1-1.5 hours. The intervention will be administered by cath lab nursing staff.
Treatment arm:
- Lignocaine 1mg/kg (maximum dose 100mg) will be given as a intravenous (IV) bolus at the start of the angiogram procedure after time-out is completed
- During the case, if analgesia is required a further bolus of 0.5mg/kg IV will be given at least 15 minutes after previous dose.
- If satisfactory analgesia is not achieved then patient will crossover to fentanyl arm
- Total lignocaine dose will be recorded

Ticagrelor will be given as a 180mg oral tablet loading dose with 250ml of water at the end of the coronary stent procedure in both arms.
Intervention code [1] 314118 0
Treatment: Drugs
Comparator / control treatment
Intravenous fentanyl will be used as the control treatment as this is standard peri-procedural analgesia currently. It will be given at the start of the angiogram procedure after time-out is completed. The angiogram and coronary stent insertion procedure typically takes 1-1.5 hours. The control treatment will be administered by cath lab nursing staff.
Dose:
- If under 70 years of age 0.75mcg/kg of Fentanyl IV will be given at the start of the case. If >70 years of age 0.5mcg/kg will be given at the start of the case.
- Further IV fentanyl boluses can be given at the discretion of the interventional cardiologist if further analgesia is required during the case
- Fentanyl IV 0.5mcg/kg mcg will be given at the end of the case at the time of administration of ticagrelor.
Ticagrelor will be given as a 180mg oral tablet loading dose with 250ml of water at the end of the coronary stent procedure in both arms.
Control group
Active

Outcomes
Primary outcome [1] 319657 0
serum ticagrelor concentration in each arm (ng/ml)
Timepoint [1] 319657 0
2 hours post ticagrelor 180mg oral load
Secondary outcome [1] 369058 0
Results of multimodal platelet function testing between 0-4 hours post ticagrelor load
Area under the ticagrelor plasma concentration-time curve between 0-4 hours
Timepoint [1] 369058 0
at time 0, 30 minutes, 1 hour, 2 hours and 4 hours post ticagrelor load
Secondary outcome [2] 369059 0
Analgesic effectiveness - numerical rating scale score
Timepoint [2] 369059 0
At start of coronary angiogram, at end of procedure and 2 hours after

Eligibility
Key inclusion criteria
Males and non-pregnant females over 18 years of age who have provided informed consent for angiography and PCI
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Out of hospital cardiac arrest
• STEMI
• Cardiogenic shock
• Morphine or opiate administration in the preceding 24 hours or regular use
• Patients with a known coagulopathy or coagulation disorder
• Allergy to fentanyl or lignocaine
• Bradycardia or evidence of AV block
• Ticagrelor or other P2Y12 inhibitor use in the preceding 10 days

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
computer coin toss simulation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis
Sample size calculation was performed based on previous pharmacodynamic data demonstrating a 25-50% reduction in the antiplatelet effects of clopidogrel with concomitant morphine administration using aggregometry assays. We calculated that 35 patients in each group would be required to identify a 20% reduction in ticagrelor’s antiplatelet effects to obtain a power of 80%, assuming a two-sided alpha of 0.05.

Continuous variables will be compared between both study arms with Student’s t-test and Mann–Whitney U test, depending on the presence or absence of the normal distribution (as assessed by the Shapiro-Wilk test). Comparisons between categorical variables were will be performed using Fisher’s exact test. Two sided p values <0.05 will be considered significant.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
2/12/2019
Actual
13/02/2020
Date of last participant enrolment
Anticipated
1/12/2020
Actual
24/12/2020
Date of last data collection
Anticipated
8/12/2020
Actual
4/01/2021
Sample size
Target
70
Accrual to date
Final
70
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 13553 0
The Alfred - Prahran
Recruitment postcode(s) [1] 26177 0
3004 - Prahran

Funding & Sponsors
Funding source category [1] 302411 0
Other Collaborative groups
Name [1] 302411 0
Baker IDI
Country [1] 302411 0
Australia
Funding source category [2] 303958 0
Hospital
Name [2] 303958 0
Alfred Hospital - Special purpose fund
Country [2] 303958 0
Australia
Primary sponsor type
Hospital
Name
Alfred Health
Address
Alfred Hospital
55 Commercial Rd
Prahran
Victoria, 3004
Country
Australia
Secondary sponsor category [1] 302308 0
None
Name [1] 302308 0
Address [1] 302308 0
Country [1] 302308 0
Other collaborator category [1] 280982 0
Other Collaborative groups
Name [1] 280982 0
Baker Heart and Diabetes Institute
Address [1] 280982 0
75 Commercial Rd
Melbourne
VIC 3004
Country [1] 280982 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303080 0
Alfred Health HREC
Ethics committee address [1] 303080 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 303080 0
Australia
Date submitted for ethics approval [1] 303080 0
29/04/2019
Approval date [1] 303080 0
17/09/2019
Ethics approval number [1] 303080 0

Summary
Brief summary
This randomised study will evaluate the efficacy of intravenous lignocaine as an alternative analgesic in patients undergoing percutaneous coronary intervention to fentanyl which is standard of care. The rationale behind this study relates to multiple biochemical studies demonstrating delayed absorption of antiplatelet agents when opioid analgesia is administered. Furthermore, these studies demonstrate that by delaying gastric absorption, the antiplatelet effects of ticagrelor based on platelet function are also delayed. Retrospective analysis of large clinical studies suggest poorer clinical outcomes in patients treated wtih opioid analgesia. Patients admitted and consented for coronary angiography will be recruited from The Alfred Hospital, Victoria. Patients presenting with STEMI, cardiogenic shock, out of hospital cardiac arrest, previous opioid or P2Y12 administration, coagulopathy or allergy to opioids or lignocaine will be excluded. Patients undergoing percutaneous coronary intervention will be randomised to receive either lignocaine or fentanyl as follows:
For patients allocated to lignocaine:
- Lignocaine 1mg/kg (maximum dose 100mg) will be given as a bolus at the start of the case
- During the case, if analgesia is required a further bolus of 0.5mg/kg will be given.
- If satisfactory analgesia is not achieved then patient will crossover to fentanyl arm
- Total lignocaine dose will be recorded

For patients allocated to fentanyl:
- If under 70 years of age 0.75mcg/kg of Fentanyl IV will be given at the start of the case. If >70 years of age 0.5mcg/kg will be given at the start of the case.
- Further IV fentanyl boluses can be given at the discretion of the interventional cardiologist if further analgesia is required during the case
- Fentanyl IV 0.5mcg/kg mcg will be given at the end of the case at the time of administration of ticagrelor.

Study endpoints will evaluate the efficacy of intravenous lignocaine in terms of analgesic efficacy and assess the interaction in terms of platelet function studies and pharmacokinetic analysis. This will determine if lignocaine is a safe, effective alternative analgesic which does not interact with antiplatelet agents.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92398 0
A/Prof Dion Stub
Address 92398 0
Heart Centre
Level 3, Alfred Hospital
55 Commercial Rd,
Prahran
VIC 3004
Country 92398 0
Australia
Phone 92398 0
+61 390762000
Fax 92398 0
Email 92398 0
d.stub@alfred.org.au
Contact person for public queries
Name 92399 0
Dr Himawan Fernando
Address 92399 0
Heart Centre
Level 3, Alfred Hospital
55 Commercial Rd,
Prahran
VIC 3181
Country 92399 0
Australia
Phone 92399 0
+61 390762000
Fax 92399 0
Email 92399 0
h.fernando@alfred.org.au
Contact person for scientific queries
Name 92400 0
Dr Himawan Fernando
Address 92400 0
Heart Centre
Level 3, Alfred Hospital
55 Commercial Rd,
Prahran
VIC 3181
Country 92400 0
Australia
Phone 92400 0
+61 390762000
Fax 92400 0
Email 92400 0
h.fernando@alfred.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
As per ethics submission, individual participant data will not be made available. However, collated data post analysis will be made available to all participants and will be included as part of a manuscript for submission to a peer-reviewed journal. Individuals will not be identifiable from data available for publication.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Himawan Fernando, Thy Duong, Kevin Huynh, Jonathan... [More Details]

Documents added automatically
No additional documents have been identified.