Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609001073291
Ethics application status
Approved
Date submitted
8/12/2009
Date registered
15/12/2009
Date last updated
5/02/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Pain relief after open radical prostate surgery: the use of a subcutaneous local anaesthetic solution.
Scientific title
Systemic lignocaine shortens length of hospital stay after open radical retropubic prostatectomy. A double-blinded, randomised, placebo-controlled multicentre trial.
Secondary ID [1] 1195 0
Nil
Universal Trial Number (UTN)
U1111-1112-8101
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate cancer 252373 0
Radical open retropubic prostatectomy 252374 0
Condition category
Condition code
Anaesthesiology 256554 256554 0 0
Pain management
Cancer 256565 256565 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients in the intervention group will receive an intraoperative intravenous infusion of 2% lignocaine (20mg/ml solution). The perioperative lignocaine protocol will be as follows: Immediately prior to surgical incision, an intravenous loading dose (1.5mg/kg) of 2% lignocaine will be administered over 10 minutes followed by an continuous infusion of intravenous 2% lignocaine at 1.5 mg/kg/hr for the duration of the operation. The duration of this operation at our institution is approximately 2 - 3 hours. At surgical closure, the intravenous infusion will be stopped and a subcutaneous infusion of 2% lignocaine will be commenced at 1.5mg/kg/hr for 24 hours postoperatively. Additional multimodal analgesia including morphine patient controlled analgesia (PCA) will be available for rescue analgesia according to routine hospital protocols for postoperative analgesia. The morphine patient controlled analgesia device will contain morphine (1mg/ml), and will be set with a 5 minute lockout and will continue for 24 hours. Multimodal analgesia will consists of paracetamol 1g orally/intravenously 6 hourly and ketorolac orally/intravenously 30mg 6 hourly (if no contraindications) for 24 hours.
Intervention code [1] 255675 0
Treatment: Drugs
Comparator / control treatment
Patients in the control group will receive an intraoperative intravenous infusion of placebo (normal saline), followed by a subcutaneous infusion of placebo (normal saline) for 24 hours postoperatively, in additional to routine multimodal analgesia including morphine patient controlled analgesia.
Control group
Placebo

Outcomes
Primary outcome [1] 253439 0
The primary outcome measure is time to home readiness.

The criteria for home readiness are as follows:
1. Full mobilisation without assistance
2. Return of gastrointestinal function (eating, drinking, bowel movement)
to normal
3. Mild pain adequately controlled with oral analgesics
4. No postopeartive nausea or vomiting
5. No evidence of infection locally (redness, tenderness) or systemically
(fever, increase in C-reactive protein or leukocyte count)
6. No other ongoing complications (bleeding, respiratory problems, deep vein thrombosis etc)
Timepoint [1] 253439 0
The primary outcome will be recorded for the duration of the patients hospital stay.
Secondary outcome [1] 262568 0
Postoperative pain at rest at the incision site using Visual Analogue Scores (VAS) 0-100mm scale.
Timepoint [1] 262568 0
Measured every 1 h for 4 h, then every 4 h during first 24 hours, and every 6-12 h during 24 - 48 h.
Secondary outcome [2] 262612 0
Postoperative pain with coughing using Visual Analogue Scores (VAS) 0-100mm scale.
Timepoint [2] 262612 0
Measured every 1 h for 4 h, then every 4 h during first 24 hours, and every 6-12 h during 24 - 48 hr.
Secondary outcome [3] 262613 0
Total morphine in milligrams of patient controlled analgesia consumption.
Timepoint [3] 262613 0
Measured every 4 hours for 24 hours.
Secondary outcome [4] 262614 0
Need for rescue analgesia (type, amount, duration).
Timepoint [4] 262614 0
Measured every 1 h for 4 h, then every 4 h during first 24 hours, and every 6-12 h during 24 - 48hr.
Secondary outcome [5] 262615 0
Need for rescue anti-emetic therapy (type, amount, duration)
Timepoint [5] 262615 0
Measured every 1 h for 4 h, every 4 h during first 24 hours, and every 6-12 h during 24 - 48 hr.
Secondary outcome [6] 262616 0
Patient satisfaction scale for pain control during study (24 hours)
(very dissatisfied, dissatisfied, neutral, satisfied, very satisfied)
Timepoint [6] 262616 0
Measured at 24 hours.
Secondary outcome [7] 262617 0
Postoperative sedations scores (0= awake and alert, 1 = occasionally drowsy but easy to rouse, 2 = often drowsy but easy to rouse, 3 = somnolent and difficult to rouse, S = sleeping
Timepoint [7] 262617 0
Measured every 1 h for 4 h, every 4 h during first 24 hours, and every 6-12 h during 24 - 48hr.
Secondary outcome [8] 262618 0
Lignocaine related side effects: circumoral paraesthesia, dizziness, headache, muscle twitching, visual or auditory hallucinations, confusion etc.
Timepoint [8] 262618 0
Measured every 1 h for 4 h, every 4 h during first 24 hours, and every 6-12 h during 24 - 48 hr.
Secondary outcome [9] 262619 0
Gastrointestinal function: time to drinking and eating, and time to first bowel function.
Timepoint [9] 262619 0
Measured at 24 hours & 48 hrs.
Secondary outcome [10] 262620 0
Urine and drain tube output.
Timepoint [10] 262620 0
Measured at 24 hours & 48 hrs.
Secondary outcome [11] 262621 0
Time to mobilise.
Timepoint [11] 262621 0
Measured at 24 hours & 48 hrs.
Secondary outcome [12] 262622 0
Reported medical complications: wound infection, pneumonia, cardiac events, thromboembolic events.
Timepoint [12] 262622 0
Measured throughout duration of hospital stay

Eligibility
Key inclusion criteria
Adults (age > 18 years < 75 years) having elective open radical prostatectomy
American Society of Anesthesiologists (ASA) physical status I-III patients
Minimum age
18 Years
Maximum age
75 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Patient refusal
American Society of Anesthesiologists (ASA) physical status > III
Moderate/severe renal impairment: serum creatinine > 200ummol/l
Chronic opioid use: 1 mg or more intravenous or 3 mg or more oral morphine per hour for a period greater than 1 month may be considered to have high-grade opioid tolerance daily oral opioids
Known allergy or intolerance to morphine or local anaesthetic
Severe hepatic insufficiency (Bilirubin > 30umol/L, Alkaline phosphatse (ALP) > 300iu/L, Alanine transaminase (ALT) > 50iu/L, Albumin < 25g/dL, International normalised ratio (INR > 1.5)
Cardiac conduction defect (second or third degree heart block or severe sinoatrial block without pacemaker)
Reduced seizure threshold defined as any patient with epilepsy or a history of adult seizures, or patients who have undergone an open cranial neurosurgical procedure within a 5-year period.
Myasthenia Gravis
Patients taking other Class I anti-arrhythmic agents or amiodarone

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)
Patients will be informed about the study and consented at the preanaesthesia admission clinic 1-2 weeks prior to surgery.

On the day of surgery, an independent anaesthetist or research nurse who is not a study investigator will open a sealed opaque randomisation envelope. The independent anaesthetist will prepare either 2% lignocaine or 0.9% saline in coded two 50 mls syringes for intraoperative use and a 2% lignocaine 200 mL flask for the postoperative infusion. The syringes and flask will be labeled 2% Trial Drug (ie each mL = 20mg) with coloured printed labels.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomization table created by a computer software (i.e., computerised sequence generation) will be preformed. For each patient, an opaque envelope containing the group assignment will be prepared, sealed and sequentially numbered. On the morning of surgery the anaesthetist will open the envelope and randomised the patients into one of the two groups described above.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
25/07/2008
Actual
25/07/2008
Date of last participant enrolment
Anticipated
31/01/2009
Actual
31/03/2009
Date of last data collection
Anticipated
Actual
Sample size
Target
76
Accrual to date
Final
76
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 256156 0
Hospital
Name [1] 256156 0
Austin Hospital
Country [1] 256156 0
Australia
Primary sponsor type
Hospital
Name
Austin Hospital
Address
Department of Anaesthesia
Studley Road, Heidelberg, 3084, Victoria
Country
Australia
Secondary sponsor category [1] 251495 0
Other
Name [1] 251495 0
Australia & New Zealand College of Anaesthetists
Address [1] 251495 0
ANZCA House, 630 St Kilda Road,
Melbourne
Victoria, 3004
Country [1] 251495 0
Australia
Other collaborator category [1] 996 0
Hospital
Name [1] 996 0
Box Hill Hospital
Address [1] 996 0
Department of Anaesthesia
16 Arnold Street
Box Hill VIC 3128
Country [1] 996 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258257 0
Austin Hospital Research Ethics Committee
Ethics committee address [1] 258257 0
Austin Hospital, Studley Road
Heidelberg, Victoria, 3084
Ethics committee country [1] 258257 0
Australia
Date submitted for ethics approval [1] 258257 0
Approval date [1] 258257 0
01/06/2008
Ethics approval number [1] 258257 0
03180
Ethics committee name [2] 258258 0
Eastern Health Research and Ethics Committee
Ethics committee address [2] 258258 0
Box Hill Hospital, 16 Arnold Street
BOX HILL, Victoria, 3128
Ethics committee country [2] 258258 0
Australia
Date submitted for ethics approval [2] 258258 0
Approval date [2] 258258 0
01/06/2008
Ethics approval number [2] 258258 0
03180

Summary
Brief summary
Postoperative pain relief for patients undergoing open radical prostatectomy (surgical removal of the prostate gland via a lower abdominal surgical incision) is provided by either strong painkillers such as intravenous morphine (delivered into the peripheral vein of the patient), or by the infusion of a local anaesthetic solution via an epidural catheter, which is inserted by an anesthetists into the epidural space that surrounds the spinal cord. The local anaesthetic solution acts by numbing the nerves around the spinal cord thereby providing pain relief from the surgical wound. One alternative method of administering the local anaesthetic solution for its beneficial effects without the inherent risks of epidural insertion is to administer the local anaesthetic solution directly into the patient’s circulation via a peripheral vein. Many well-designed studies investigating patients undergoing major abdominal surgery have shown that this method of administering the local anaesthetic solution provides excellent pain relief with minimal side effects. This technique also has beneficial effects on early postoperative return on bowel function. The administration of local anaesthetic solutions via this route is inexpensive, easy to administer, and safe. There is only one published clinical trial investigating this technique in patients undergoing radical prostatectomy. The main end point of this study was return of bowel function. However, it is not known if the addition of a systemic local anaesthetic solution with morphine accelerates postoperative recovery and shortens the duration of hospital stay. This research study will investigate this precise question.

The purpose of the study is to compare whether the use of a lignocaine infusion together with intravenous morphine reduces time to readiness for discharge compared to using intravenous morphine alone. Adult patients undergoing elective open radical prostatectomy will be invited to participate. Patients will be approached and consented for surgery in the Urology or Anaesthetic Outpatient Clinics. All patients will have general anaesthesia and surgery performed accordance to the standard practice of their caring surgeons and anaesthetists. All patients will receive intravenous morphine together with simple pain relief adjuvants such as paracetamol and non-steroidal anti-inflammatory tablets. This is standard practice at Austin Hospital for all patients undergoing this operation. Consenting patients will be randomised into 2 groups. One group will receive an infusion of a local anaesthetic solution (ligonacaine); the other group will receive a placebo solution of normal saline. Neither the patient nor anaesthetist (or any member of the surgical or nursing team) will know which group the patient has been randomised to. This study is therefore a prospective double-blinded, randomised, placebo-controlled trial. This is the gold standard experimental research design.

The main study aim will be to collect data from the patient’s postoperative records and assess when the patient is ready for hospital discharge. Other secondary end points collected will include pain and sedation scores, return of bowel function, cumulative morphine use, need for rescue pain medication and side effects of morphine and the local anaesthetic solution. Standard and specialised statistical tests will be used to analyse differences between the two groups of patients.

All patients will be managed by the Austin Hospital acute pain service guidelines, in accordance with standard practices and infusion protocols.
Trial website
Trial related presentations / publications
Weinberg L, Rachbuch C, Ting S, Howard W, Yeomans M, Gordon I, McNicol L, James K, Story D, Christophi C.A randomised controlled trial of peri-operative lidocaine infusions for open radical prostatectomy. Anaesthesia. 2016 Jan 8. doi: 10.1111/anae.13368.
Public notes

Contacts
Principal investigator
Name 30602 0
A/Prof Laurence Weinberg
Address 30602 0
Department of Anaesthesia, Austin Hospital
Studley Rd, Heidelberg Victoria Australia 3161
Country 30602 0
Australia
Phone 30602 0
+61394965000
Fax 30602 0
+61394966421
Email 30602 0
[email protected]
Contact person for public queries
Name 13849 0
A/Prof Dr Laurence Weinberg
Address 13849 0
Department of Anaesthesia
Austin Hospital
Studley Road
Heidelberg, 3084, Victoria
Country 13849 0
Australia
Phone 13849 0
+61 3 94965000
Fax 13849 0
+61394966421
Email 13849 0
[email protected]
Contact person for scientific queries
Name 4777 0
A/Prof Dr Laurence Weinberg
Address 4777 0
Department of Anaesthesia
Austin Hospital
Studley Road
Heidelberg, 3084, Victoria
Country 4777 0
Australia
Phone 4777 0
+61 3 94965000
Fax 4777 0
+61394966421
Email 4777 0
[email protected]

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No Supporting Document Provided



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