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Trial registered on ANZCTR


Registration number
ACTRN12619000621112p
Ethics application status
Submitted, not yet approved
Date submitted
13/12/2018
Date registered
26/04/2019
Date last updated
26/04/2019
Date data sharing statement initially provided
26/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of the local anaesthetic lidocaine and the antibiotic doxycycline to help protect the blood vessel lining in patients undergoing heart surgery.
Scientific title
Preserving the endothelial glycocalyx in patients undergoing cardiopulmonary bypass. A prospective randomised interventional pilot study of doxycycline and lidocaine.
Secondary ID [1] 296877 0
None
Universal Trial Number (UTN)
U1111-1225-5165
Trial acronym
LiDEG
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ischaemic Heart Disease 310803 0
Valvular Heart Disease 310804 0
Aortic Disease 310805 0
Condition category
Condition code
Anaesthesiology 309478 309478 0 0
Anaesthetics
Cardiovascular 309479 309479 0 0
Coronary heart disease
Cardiovascular 309480 309480 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cardiovascular 309481 309481 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants, patients undergoing elective or urgent surgery requiring cardiopulmonary bypass, will be randomised to 1 of 3 equal groups. The groups consist of a control group, a group receiving intravenous lidocaine (1.5mg/kg bolus followed by 2mg/kg/hr infusion) during their operation, a group receiving oral doxycycline (200mg tablet) in the holding bay 0-90mins prior to being brought into theatre.
Intervention code [1] 313154 0
Treatment: Drugs
Comparator / control treatment
A group will receive neither treatment and their samples will be used as the control.
Control group
Active

Outcomes
Primary outcome [1] 308440 0
Change in syndecan-1 (Biochemical marker of endothelial glycocalyx injury).
Expressed as a fold increase of baseline (pre-induction) level.
Assessed by serial serum assays.
Timepoint [1] 308440 0
Serial measurements,
1. pre induction through invasive monitoring line.
2. after protamine administration (heparin reversal after end of cardiopulmonary bypass)
3. admission to ICU
4. 6 hours post operatively.
5. First post operative morning

(Prior work has a peak at 6 hours with diminishing levels observed by the morning of day 1 post op)
Secondary outcome [1] 354961 0
Vasopressor (blood pressure support) requirements. (Dose of noradrenaline measured in micrograms per minute)


This information is automatically recorded from "smart" infusion pumps and is available from the electronic record in ICU
Timepoint [1] 354961 0
Requirement and agent immediately after arrival in ICU and
Requirement at 6 hours post operatively
Secondary outcome [2] 354962 0
Presence or absence of atrial fibrillation
Timepoint [2] 354962 0
90 days post operatively
This is already routinely screened for and recorded in the electronic notes in all patients
Secondary outcome [3] 354963 0
Incidence of chronic post surgical pain
Timepoint [3] 354963 0
90 days post operatively. via telephone.
"QoR 15" quality of recovery
study-specific questionnaire
Secondary outcome [4] 354964 0
Kidney dysfunction
Timepoint [4] 354964 0
maximum serum creatinine recording within 72 hours post operatively expressed as a fold increase of baseline creatinine.
or
New renal replacement therapy within 72 hours of operation

All info routinely recorded in all patients
Secondary outcome [5] 354965 0
inflammation. Cytokine interleukin 6

Expressed as a fold increase of baseline (pre-induction) level.
Assessed by serial serum assays.
Timepoint [5] 354965 0
Serial measurements,
1. pre induction through invasive monitoring line.
2. after protamine administration (heparin reversal after end of cardiopulmonary bypass)
3. admission to ICU
4. 6 hours post operatively.
5. First post operative morning
Secondary outcome [6] 354966 0
Bleeding- Volume in combined pleural and pericardial drains (drain from common tube)

Expressed in millilitres
Timepoint [6] 354966 0
total 12 hour post operative volume

routinely measured in all patients and recorded in electronic record
Secondary outcome [7] 368153 0
Use of red cell transfusion
Timepoint [7] 368153 0
Within 72 hours of operation. Including intraoperative transfusion.

Routinely recorded.
Secondary outcome [8] 368155 0
Use of any non red cell blood products (any of fresh frozen plasma, platelets, prothrombin complex)
(indicates coagulation disorders)
Timepoint [8] 368155 0
Within 72 hours of operation. Including intraoperative use.

Routinely recorded.
Secondary outcome [9] 368156 0
inflammation. Cytokine interleukin 8

Expressed as a fold increase of baseline (pre-induction) level.
Assessed by serial serum assays.
Timepoint [9] 368156 0
Serial measurements,
1. pre induction through invasive monitoring line.
2. after protamine administration (heparin reversal after end of cardiopulmonary bypass)
3. admission to ICU
4. 6 hours post operatively.
5. First post operative morning
Secondary outcome [10] 368158 0
total White cell count

Expressed as a fold increase of baseline (pre-induction) level.
Assessed by serial serum assays.
Timepoint [10] 368158 0

Serial measurements,
1. pre induction through invasive monitoring line.
2. after protamine administration (heparin reversal after end of cardiopulmonary bypass)
3. admission to ICU
4. 6 hours post operatively.
5. First post operative morning

Eligibility
Key inclusion criteria
All adult patients with capacity to consent undergoing operations requiring cardiopulmonary bypass.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unable to consent/ refusal.
Hypersensitivity to study drugs.
Operations not requiring cardiopulmonary bypass.
Known or suspected liver disease
Alcoholism

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)
3 equal groups of 20 (totalling 60) will be written on paper concealed in opaque envelopes.
This will then be broken into 5 bundles of 12 (with 4 from each of the 3 treatment arms).
Envelopes within each bundle will then be shuffled repeatedly to ensure randomisation.

This technique is to facilitate interim analysis with equal numbers from each group represented.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Factorial
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Comparisons will be made using means paired analyses, computed with “PRISM” statistical software. Being a pilot we are in the hypothesis generating phase and have not performed power analysis.
It will be analysed using a "per protocol" approach.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 12723 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [2] 12724 0
Mount Hospital - Perth
Recruitment postcode(s) [1] 25150 0
6150 - Murdoch
Recruitment postcode(s) [2] 25151 0
6000 - Perth

Funding & Sponsors
Funding source category [1] 301446 0
Charities/Societies/Foundations
Name [1] 301446 0
Spinnaker Foundation
Address [1] 301446 0
Alma Street, Room Fremantle Hospital Alma Street, Room 27B, G Block27B, G Block, Fremantle WA 6160
Country [1] 301446 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Hearty and Lung Institute of Western Australia
Address
Care of: Dept of Anaesthesia (Cardiothoracic division)
Fiona Stanley Hospital
11 Robin Warren Dr,
Murdoch
WA 6150
Australia
Country
Australia
Secondary sponsor category [1] 301137 0
Hospital
Name [1] 301137 0
Fiona Stanley hospital
Address [1] 301137 0
11 Robin Warren Dr, Murdoch WA 6150
Country [1] 301137 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 302181 0
South Metropolitan Health Service Human Research Ethics Committee
Ethics committee address [1] 302181 0
Fiona Stanley Hospital, 11 Robin Warren Dr, Murdoch WA 6150
Ethics committee country [1] 302181 0
Australia
Date submitted for ethics approval [1] 302181 0
25/03/2019
Approval date [1] 302181 0
Ethics approval number [1] 302181 0

Summary
Brief summary
Heart surgery is known to cause damage to the inner lining of blood vessels called the "endothelial glycocalyx". This damage can affect bleeding, swelling and inflammation which can harm organs and delay recovery after surgery. Damage to this layer can be measured using special blood tests. Currently there are no drugs used to protect this layer during surgery. Some experiments have shown the commonly used local anaesthetic "lidocaine" and the antibiotic "doxycycline" may be of benefit to protect this layer. We propose a project in which patients undergoing heart surgery are randomly allocated to receive one or other of the medicines or neither (a "control" group). Blood tests will indicate if these medicines have an effect on this layer. We hypothesise that lidocaine and or doxycycline may protect the endothelial glycocalyx during heart surgery.
Trial website
NA
Trial related presentations / publications
NA
Public notes
NA

Contacts
Principal investigator
Name 89394 0
Dr Mark Johnson
Address 89394 0
Dept. of Anaesthesia,
Fiona Stanley Hospital,
11 Robin Warren Dr, Murdoch WA 6150
Country 89394 0
Australia
Phone 89394 0
+61 474190065
Fax 89394 0
Email 89394 0
Mark.Johnson@health.wa.gov.au
Contact person for public queries
Name 89395 0
Dr Mark Johnson
Address 89395 0
Dept. of Anaesthesia,
Fiona Stanley Hospital,
11 Robin Warren Dr, Murdoch WA 6150
Country 89395 0
Australia
Phone 89395 0
+61 474190065
Fax 89395 0
Email 89395 0
Mark.Johnson@health.wa.gov.au
Contact person for scientific queries
Name 89396 0
Dr Mark Johnson
Address 89396 0
Dept. of Anaesthesia,
Fiona Stanley Hospital,
11 Robin Warren Dr, Murdoch WA 6150
Country 89396 0
Australia
Phone 89396 0
+61 474190065
Fax 89396 0
Email 89396 0
Mark.Johnson@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not required. Data will be analysed by group.
What supporting documents are/will be available?
No other documents available
Summary results
No Results