Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612001243808
Ethics application status
Approved
Date submitted
16/05/2012
Date registered
26/11/2012
Date last updated
12/01/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Redefining pain management after cardiac surgery to improve intensive care and hospital length of stay: a randomised pilot trial.
Scientific title
Redefining pain management after coronary artery graft surgery to improve intensive care and hospital length of stay: a randomised pilot trial.
Secondary ID [1] 280502 0
Nil
Universal Trial Number (UTN)
Trial acronym
PAINLESS pilot trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary Artery Disease 286480 0
Condition category
Condition code
Cardiovascular 286739 286739 0 0
Coronary heart disease
Anaesthesiology 286740 286740 0 0
Pain management
Physical Medicine / Rehabilitation 286741 286741 0 0
Physiotherapy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Prior to the closeure of the sternotomy wound post coronary artery graft surgery (CAGS), eligible participants will be randomly allocated to receive either 1: usual care, 2: saline (placebo) via On-Q Pain Buster device or 3: continuous infusions via the On-Q Pain Buster device.
Treatment assignment of the infusion solution will remain blinded to study personnel. An un-blinded pharmacist will phone the NHMRC Clinical Trials Centre remote telephone randomisation service. A computer generated programme makes treatment assignment based on stratification by minimisation.
The placebo and active agent pre-loaded bags are stored in the clinical trials refridgerator with a 3 month expiry. A log is kept in the pharmacy with access only by the trial pharmacist. The bag is then blinded and sent to theatre. If treatment assignment is to the trial device, the pharmacist will prepare the appropriate solution (400ml of normal saline or 0.5% ropivacaine solution in the On-Q Pain Buster device plus a 10ml syringe of matched solution which is a part of the 400ml solution) to the operating theatre labeled as "Ropivacaine/Placebo:PAINLESS TRIAL".
The blinded, scrubbed, surgical registered nurse will load the On-Q Pain Buster device which will be tunnelled parasternally in a subpectoral position by one of the investigating surgeons.
The On-Q Pain Buster system utilises a balloon-type elastomeric pump filled with a local anaesthetic that is automatically delivered to the surgical site by the On-Q soaker catheter. Dual catheters have a flow restrictor, one on each catheter side after the bifurcation above the luer lock connection just before the soaker catheters. This ensures that the flow rate to both catheters is equal and prevents the fluid taking the least path of resistance or the lowest catheter port. A small dressing will be placed over the catheter.
Arm1(usual care) will receive standard pain therapies with patient controlled analgesia (PCA), intravenous (IV) morphine or fentanyl, at the discretion of the ICU or pain teams, and oral analgesia
Arm2 will receive normal saline through the On-Q device and usual care
Arm 3 (experimental group) will receive ropivacaine by the delivery system and usual care as needed. The recommended maximum daily dose of ropivacaine will not be exceeded and will be administered within the recommended standard. The 400ml elastomeric pump will be filled with ropivacaine 10x20ml 1% Naropin ampoules and normal saline (200ml) yielding a ropivacaine concentration of 5mg/ml (0.5%). The On-Q pump will deliver 5mg/ml of ropivacaine 0.5% via the two tunnelled catheters at a total rate of 4ml/hr. Therefore the total hourly dose is 20mg resulting in a total 24hr dosage of 480mg of ropivacaine.
For arm 2 and arm 3, prior to the commencement of the infusion, a 10ml bolus dose of the solution (50mg if the solution is ropivacaine or 10ml of saline if placebo) will be given by the cardiothoracic surgeon through the catheters. The infusion will commence at a total rate of 4mls/hr. The catheters will stay in place until the 400ml elastomeric pump is emptied. This will take approximately 4 days (96 hours) at which point the On-Q Pain Buster device will be removed by trained registered nurses (RN) on the cardiothoracic ward.
Surgeons, intensive care specialists, registrars, junior medical officers and nursing staff will be responsible for monitoring signs of toxicity. Premonitory signs of toxicity will be documented in the data sheet. Such symptoms include: dysarthria, muscular rigidity or twitching, unconsciousness, convulsions, hypoxia, hypercapnia, apnoea, severe hypotension or tachycardia, paraesthesia, temperature elevation, rigors (chills), headache and dizziness, vomitting, urinary retention, hypothermia, back pain, dyspnoea, insomnia, chest pain, pain and oliguria (more than 1% risk)
In the event of toxicity, the catheters will be clamped immediately. Subsequently treatment will require securing a patent airway and ventilating with 100% oxygen. In the event of cardiac toxicity, sodium bicarbonate intravenous 1-2meq/kg will be required to treat cardiac toxicity due to sodium channel blockade. The Lipid Rescue Protocol will be observed in the operating theatre (OT) and copies of the rescue protocol will be made available in ICU, cardiothoracic ward and in the OT. Further management will be decided by the intensivist and the cardiothoracic surgeons. Intravenous access will be maintained until the Pain Buster is removed.
The use of the continuous ropivacaine infusion will compliment, not replace existing pain therapies hence patients will have the use of standard intravenous PCA and oral pain medication once the PCA narcotics are ceased as per curent standard practice. The pain team will review this post-operatively. PCA requirements will be monitored for the purpose of this study.

Post operative period
Suitability for extubation and clearance from intensive care will be assessed and documented by the study intensivist and surgeon using standardised criteria. Visual analogue scores (VAS) for pain will be measured every 12 hours for the duration of the local anesthetic infusion or for 4 days (whichever is longer) and before and after physiotherapy treatment sessions. Data on PCA, intravenous and oral analgesia requirements will be collected. The distance participants walk with the physiotherapist in each post operative day will be recorded. The pulmonary function test (forced expiratory volume in 1 second, functional vital capacity and peak expiratory flow) will be conducted pre operatively and on post operative day 3 prior to removal of the device. The discharge date from ICU and hospital will also be recorded.
Preoperatively and at 3 and 6 months participants who agreed to chronic pain substudy will be contacted to complete a chronic pain assessment survey.
Intervention code [1] 284867 0
Prevention
Intervention code [2] 284868 0
Treatment: Drugs
Comparator / control treatment
Both the placebo and usual care groups will be deemed as the control groups in this pilot trial
Control group
Placebo

Outcomes
Primary outcome [1] 287134 0
Greater than 80% of participants' data sheet will be completed, i.e. less than 20% of participants' data sheet will have missing data.
Timepoint [1] 287134 0
30 months
Primary outcome [2] 287253 0
All 75 participants will be recruited within 30months of commencing the pilot trial.
English speaking patients undergoing CAGS only in the Cardiothoracic Departments at Liverpool and Royal Prince Alfred Hospitals are eligible for consideration for inclusion into this study. Various sources are being used to recruit patients including cardiology and cardiothoracic surgery team referrals, cardiothoracic case manager referrals and liaison with ward nursing staff and cardiology registrars These patients will be recruited from the two Liverpool hHospitals in the Sydney South Western Sydney and Sydney Area Health Service (SSWAHS)Local Health Networks. Those who give informed consent for this study will be included. The study nurse will keep the record of the patients who are recruited.
Timepoint [2] 287253 0
30 months
Secondary outcome [1] 297757 0
Proportion of participants who are meet discharge criteria from intensive care unit within 48 hours. Suitability for extubation and clearance from intensive care will be assessed and documented by the study intensivist and surgeon using standardised criteria.
Timepoint [1] 297757 0
30 months
Secondary outcome [2] 299694 0
Proportion of participants needing less than 25 mg of morphine equivalent in the first 48 hour. Data on PCA, intravenous and oral analgesia requirements will be collected.
Timepoint [2] 299694 0
30 months
Secondary outcome [3] 299695 0
Proportion of patricipants walking greater than 80m on post operative day 3. The distance participants walked is measured by the treating physiotherapists each day.
Timepoint [3] 299695 0
30 months
Secondary outcome [4] 299841 0
Pain scores recorded by ropivacaine group will be lower than other groups at specified time points. Visual analogue scores (VAS) for pain will be measured per participants
Timepoint [4] 299841 0
VAS is scored at every 12 hours for the duration of the local anesthetic infusion or for 4 days (whichever is longer) and before and after physiotherapy treatment sessions.4 post operative days per participant.
Secondary outcome [5] 299842 0
Proportion of participants discharged from hospital in less than 5 days. This will be obtained through medical records
Timepoint [5] 299842 0
30 months
Secondary outcome [6] 299843 0
Change in pulmonary function (FEV1, FVC and PEF) from pre op and at post operative day 3. Every participants will perform spirometry by the treating physiotherpist at pre op and at post operative day 3. These two results will be compared.
Timepoint [6] 299843 0
30 months
Secondary outcome [7] 299844 0
Proportion of patients experiencing chronic pain at 3 months and 6 months. The chronic pain survey will be sent out to participants by mail and these will be collected.
Timepoint [7] 299844 0
36 months. (6 months after the last recruited participant)
Secondary outcome [8] 300061 0
Proportion of patients extubated within 24 hours
Timepoint [8] 300061 0
30 months
Secondary outcome [9] 300062 0
Proportion of patients discharged from physiotherapy on day 4 post op. The treating physiotherapist will note the date of when the participants are discharged from physiotherapy discharge criteria.
Timepoint [9] 300062 0
30 months

Eligibility
Key inclusion criteria
The participant must meet ALL the criteria listed below for entry:
1. Participant speaks English
2. Participant can read English
3. Participant must be 18 years or older, and may be of either sex and of any race.
4. Participant is scheduled or will be scheduled for Coronary Artery Graft Surgery (CAGS) with at least one left internal mammary artery
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The participant will be excluded from entry if ANY of the criteria listed below are met:
1. Hypersensitivity to amide-type local anesthetics, verapamil, ciprofloxacin, and norfloxacin.
2. Women of childbearing potential
3. Current severe congestive heart failure (NYHA heart failure class more than and equal to 3).
4. Cardiogenic shock (systolic blood pressure more or equal to 90mm/Hg with or without inotropes, or on inotropes) before randomisation.
5. Left ventricular ejection fraction (LVEF) < 30% (or more than mild dysfunction on echocardiogram).
6. Acute/chronic renal impairment (creatinine level of more or equal to 160umol/L)
7. Significant liver disease (bilirubin level of > 2x the upper limit of normal), inadequate haematologic function (haemoglobin level of < 90g/L, white blood cell count of < 2.5 x 10(9)/L, neutrophil count of less than 1.0 x 10(9)/L, and platelet count of <100 x 10(9)/L).
8. Severe vasculopathy with significant thrombo-occlusive thoracoabdominal aortic disease
9. Logistic EuroSCORE risk of mortality more than and equal to 6%.
10. Use of fluvoxamine (Luvox) at the time of consent.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The participants will be recruited for the study at the time of pre operative clinic as outpatients or at preoperative assessment while inpatient. The participants attend preoperative clinic if their scheduled operation is within 4 weeks. Participants will be randomly allocated to either arm 1, arm 2 or arm 3. The allocation will be by interactive voice randomisation system conducted by the University of Sydney NHMRC Clinical Trials Centre.
Treatment allocation will remain blinded to study personnel except for the instance of the Arm 1
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Once eligibility has been confirmed, participants will be allocated in equal numbers to one of the three treatment groups using a computer generated minimisation randomisation method. This is to ensure good balance in important prognostic factors. The factors included in the randomisation scheme will include: 1 age, 2 gender, 3 left ventricular ejection fraction, and 4 creatinine. Treatment allocation will remain blinded to study personnel.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
nil
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
16/02/2010
Actual
11/02/2010
Date of last participant enrolment
Anticipated
Actual
10/09/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
75
Accrual to date
Final
75
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 5291 0
2020
Recruitment postcode(s) [2] 5292 0
2170
Recruitment postcode(s) [3] 5293 0
2555
Recruitment postcode(s) [4] 5294 0
2560
Recruitment postcode(s) [5] 5295 0
2168
Recruitment postcode(s) [6] 5296 0
2566
Recruitment postcode(s) [7] 5297 0
2176
Recruitment postcode(s) [8] 5298 0
2570
Recruitment postcode(s) [9] 5299 0
2571
Recruitment postcode(s) [10] 5300 0
2164
Recruitment postcode(s) [11] 5301 0
2165
Recruitment postcode(s) [12] 5302 0
2165
Recruitment postcode(s) [13] 5303 0
2573
Recruitment postcode(s) [14] 5304 0
2179
Recruitment postcode(s) [15] 5305 0
2760
Recruitment postcode(s) [16] 5306 0
2177
Recruitment postcode(s) [17] 5307 0
2575
Recruitment postcode(s) [18] 5308 0
2569
Recruitment postcode(s) [19] 5309 0
2675

Funding & Sponsors
Funding source category [1] 285258 0
Charities/Societies/Foundations
Name [1] 285258 0
The Australian and New Zealand Society of Cardiac and Thoracic Surgeons, Research Foundation Grant
Country [1] 285258 0
Australia
Funding source category [2] 285259 0
Commercial sector/Industry
Name [2] 285259 0
I-Flow Cooperation
Country [2] 285259 0
United States of America
Funding source category [3] 285260 0
Commercial sector/Industry
Name [3] 285260 0
Astra Zeneca Australia
Country [3] 285260 0
Australia
Primary sponsor type
Hospital
Name
Cardiac Surgery, Intensive Care Unit and Physiotherapy Department at Liverpool Hospital
Address
Cnr Goulburn and Elizabeth Streets,
Liverpool, NSW 2170
Country
Australia
Secondary sponsor category [1] 284120 0
None
Name [1] 284120 0
Address [1] 284120 0
Country [1] 284120 0
Other collaborator category [1] 260800 0
University
Name [1] 260800 0
University of Sydney NHMRC Clinical Trials Centre
Address [1] 260800 0
Levels 4-6, Medical Foundation Building
92-94 Parramatta Rd,
Camperdown, NSW 2050
Country [1] 260800 0
Australia
Other collaborator category [2] 260801 0
University
Name [2] 260801 0
Faculty of Health Sciences, Physiotherapy, University of Sydney
Address [2] 260801 0
75 East St
Lidcombe, NSW 2141
Country [2] 260801 0
Australia
Other collaborator category [3] 260802 0
Hospital
Name [3] 260802 0
Cardiac Surgery, Physiotherapy and Baired Institue, Royal Prince Alfred Hospital
Address [3] 260802 0
Suite 305
100 Carillon Ave
Newtown, NSW 2042
Country [3] 260802 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287275 0
Human Research Ethics Committee (Western Zone)
Ethics committee address [1] 287275 0
Ethics committee country [1] 287275 0
Australia
Date submitted for ethics approval [1] 287275 0
24/11/2008
Approval date [1] 287275 0
24/06/2009
Ethics approval number [1] 287275 0
08/LPOOL/263
Ethics committee name [2] 287276 0
Human Research Ethics Committee (Eastern Zone)
Ethics committee address [2] 287276 0
Ethics committee country [2] 287276 0
Australia
Date submitted for ethics approval [2] 287276 0
09/11/2011
Approval date [2] 287276 0
01/12/2011
Ethics approval number [2] 287276 0
11/RPAH/499

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34186 0
A/Prof Rebecca Dignan
Address 34186 0
Department of Cardiothoracic Surgery,
Liverpool Hospital
Elizabeth street,
Liverpool NSW 2170
Country 34186 0
Australia
Phone 34186 0
+61 87383000
Fax 34186 0
Email 34186 0
[email protected]
Contact person for public queries
Name 17433 0
Dr. Rebecca Dignan
Address 17433 0
Associate Professor, Senior Cardiothoracic Surgeon
Liverpool Hospital
Cnr Goulburn and Elizabeth Streets,
Liverpool, NSW 2170
Country 17433 0
Australia
Phone 17433 0
+61 2 9828 3000
Fax 17433 0
Email 17433 0
[email protected]
Contact person for scientific queries
Name 8361 0
Dr. Rebecca Dignan
Address 8361 0
Associate Professor, Senior Cardiothoracic Surgeon
Liverpool Hospital
Cnr Goulburn and Elizabeth Streets,
Liverpool, NSW 2170
Country 8361 0
Australia
Phone 8361 0
+61 2 9828 3000
Fax 8361 0
Email 8361 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIDoes regional anaesthesia after coronary artery bypass graft surgery improve pain control and walking distance? A RCT2015https://doi.org/10.1016/j.physio.2015.03.3411
EmbaseDoes continuous infusion of local anaesthesia improve pain control and walking distance after coronary artery bypass graft surgery? A randomised controlled trial.2017https://dx.doi.org/10.1016/j.physio.2017.02.002
N.B. These documents automatically identified may not have been verified by the study sponsor.