Trial from ClinicalTrials.gov

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Trial ID
NCT02449720
Ethics application status
Date submitted
28/04/2015
Date registered
28/04/2015
Date last updated
23/03/2017

Titles & IDs
Public title
Intraperitoneal Local Anaesthetic in Bowel Surgery
Scientific title
The Effect of Intraperitoneal Local Anaesthetic on Functional Recovery Following Bowel Resection: A Prospective Randomised Blinded Trial
Secondary ID [1] 0 0
150219
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Disorders 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: drugs - Ropivacaine
Treatment: drugs - 0.9% Saline

Active Comparator: Laparoscopic Bowel Surgery: IPLA - Participants will undergo laparoscopic bowel surgery. Both on entry into the abdominal cavity and prior to dissection and post-operation but prior to closure of abdominal wall a 50 ml loading dose of IPLA (0.2% Ropivacaine) solution will be distributed throughout the abdomen. Following these bolus doses an ON-Q Painbuster continuous infusion pump will be placed in close proximity to the operative region of greatest dissection and a 10ml/hr intraperitoneal infusion of IPLA (0.2% Ropivacaine, 20mg/hr) solution commenced immediately post-operation and continued for 48 hrs without disruption.

Placebo Comparator: Laparoscopic Bowel Surgery: Control - Participants will undergo laparoscopic bowel surgery. Both on entry into the abdominal cavity and prior to dissection and post-operation but prior to closure of abdominal wall a 50 ml loading dose of Control (0.9% Saline, 20mg/hr) solution will be distributed throughout the abdomen. Following these bolus doses an ON-Q Painbuster continuous infusion pump will be placed in close proximity to the operative region of greatest dissection and a 10ml/hr intraperitoneal infusion of Control (0.9% Saline, 20mg/hr) solution commenced immediately post-operation and continued for 48 hrs without disruption.

Active Comparator: Open Bowel Surgery: IPLA - Participants will undergo open bowel surgery. Both on entry into the abdominal cavity and prior to dissection and post-operation but prior to closure of abdominal wall a 50 ml loading dose of IPLA (0.2% Ropivacaine) solution will be distributed throughout the abdomen. Following these bolus doses an ON-Q Painbuster continuous infusion pump will be placed in close proximity to the operative region of greatest dissection and a 10ml/hr intraperitoneal infusion of IPLA (0.2% Ropivacaine, 20mg/hr) solution commenced immediately post-operation and continued for 48 hrs without disruption.

Placebo Comparator: Open Bowel Surgery: Control - Participants will undergo open bowel surgery. Both on entry into the abdominal cavity and prior to dissection and post-operation but prior to closure of abdominal wall a 50 ml loading dose of Control (0.9% Saline, 20mg/hr) solution will be distributed throughout the abdomen. Following these bolus doses an ON-Q Painbuster continuous infusion pump will be placed in close proximity to the operative region of greatest dissection and a 10ml/hr intraperitoneal infusion of Control (0.9% Saline, 20mg/hr) solution commenced immediately post-operation and continued for 48 hrs without disruption.


Treatment: drugs: Ropivacaine
Intraperitoneal instillation and infusion

Treatment: drugs: 0.9% Saline
Intraperitoneal instillation and infusion

Intervention code [1] 0 0
Treatment: drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline of the Surgical Recovery Scale to Day 45 - The postoperative domains of recovery of fatigue, and the post-discharge return to normal functioning in both cognition (concentration) and activities of daily living will be assessed using the Surgical Recovery Scale, previously validated for use following bowel surgery.
Timepoint [1] 0 0
Baseline (preoperative), and postoperative days 1, 3, 7, 30 and 45
Secondary outcome [1] 0 0
Change in Pain Over Time to Day 7 (Subjective) - Postoperative pain at rest and with movement (defined as coughing) will be evaluated using a 100mm Visual Analogue Scale with the end-points labelled "no pain" and "the worst possible pain" for each of: I. somatic pain (incisional pain in the abdominal wall that the patient can touch) II. visceral pain (deep, dull, inside the abdomen) III. shoulder tip pain
Timepoint [1] 0 0
At postoperative hours 3, 6, 12, 24, 48, and 72, and at day 7
Secondary outcome [2] 0 0
Change in Pain Over Time to day 3 (Objective) - Total opioid analgesia use during the postoperative day 1, 2, and 3 prior to discharge will be recorded and quantified using the Mean Equivalent Daily Dose (MEDD) method. Initially this will be parenteral fentanyl consumption, recorded daily in the patient controlled analgesia (PCA) device until removal of PCA. Then this will be prn tramadol, or other opioid as charted, until discharge.
Time to first PCA button press, and the number of PCA button presses will also be recorded as sometimes patients would like more analgesia than the PCA is able to administer.
Timepoint [2] 0 0
Postoperative day 1, 2, and 3
Secondary outcome [3] 0 0
Recovery of Normal Bowel Function - Time to tolerating oral diet and to first postoperative flatus, and bowel motion will be recorded. Post-operative antiemetic use will be recorded, as will number of episodes of vomiting. The length of time requiring postoperative intravenous fluid will be recorded. The requirement for insertion of naso-gastric tube will be recorded.
Timepoint [3] 0 0
Inpatient postoperative period (variable), and expected duration of 3-7 days.
Secondary outcome [4] 0 0
Time to Readiness for Discharge - The time to readiness for discharge (TRD) is a validated measurement of short-term recovery after colorectal surgery. TRD and actual length of stay (LOS) will be recorded.
Discharge criteria will be defined as
Passage of flatus or bowel motion, tolerance of oral diet and absence of nausea and vomiting.
Mobilisation back to baseline function.
Analgesia requirement managed with oral tablets only.
Willingness to be discharged home. Readmission, defined as unplanned return to hospital within 30 day and requiring an overnight admission, will be recorded.
Total hospital stay will be recorded as LOS + readmission LOS.
Timepoint [4] 0 0
up to 30 days
Secondary outcome [5] 0 0
Operative Complications - All complications that occur within a 30d postoperative period will be recorded. Complications will be recorded and graded using the Clavien-Dindo classification system.
Timepoint [5] 0 0
30 days post operation

Eligibility
Key inclusion criteria
- The study population will include adults from the Central Adelaide Local Health
network catchment area, South Australia.

- Patients known to the Colorectal Surgical Unit who have provided informed consent to
undergo elective large bowel resection for any indication or undergoing reversal of
Hartmann's Procedure will be invited to participate in this study.

- Potential participants will then be provided with an Information Sheet and encouraged
to take the time to read it, discuss it with anyone they like, and ask any questions
they have prior to deciding if they wish to participate. They will be reassured that
participation is voluntary and there is no disadvantage to them if they decide not to
participate.

- After obtaining informed consent, eligibility for inclusion will be determined based
on health questions and blood results.
Minimum age
18 Years
Maximum age
90 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Under 18 years of age or over age 90.

- Allergy to local anaesthetic.

- Underlying medical conditions requiring deviation from the proposed anaesthetic
protocol i.e., use of spinal or epidural anaesthesia rather than general anaesthesia.

- American Society of Anesthesiologists (ASA) >=4 due to the higher likelihood or
morbidity and mortality, which may confound resulting data.

- Severe underlying cardiovascular disease including conduction abnormalities, ischaemic
heart disease or congestive heart failure, or use of amiodarone as a regular
medication due to a higher risk or cardiac arrest under general anaesthetic or during
use of local anaesthesia.

- Chronic Renal Failure (CRF) Stage 3 (GFR > 60 based on two samples a minimum 90d
apart).

- The pharmacokinetics of ropivacaine is not affected by renal failure although the
renal clearance of its main metabolite (S)-2',6'-pipecoloxylidide (PPX) correlates
with creatinine clearance, non-renal clearance compensates for reduced renal clearance
in most patients.

- GFR will be calculated using the Cockcroft Gault equation for creatinine clearance
(CrCl) : CrCl ml/min = [140-age(years)] x bodyweight (kg) / R x serum creatinine
(micromol/L)

- R = 0.815 for males, 0.85 for females

- Hepatic dysfunction of Child-Pugh class B or C. Patients with end-stage liver disease
have about a 60% lower mean ropivacaine clearance than healthy subjects and are thus
expected to have over two-fold higher steady-state ropivacaine plasma concentrations
during a continuous ropivacaine infusion.

- Concurrent or recent (within 3 months) use of fluvoxamine, enoxacin, ketoconazole, or
cimetidine. These are potent CYP (cytochrome P450) 1A2, 2E1, or 3A4 inhibitors that
have been shown to reduce ropivacaine clearance in vivo or in in vitro models.
Potential participants concurrently using other potent CYP1A2, 2E1, or 3A4 inhibitors,
where it is unclear if there is an effect on ropivacaine clearance, will be included
or excluded from the study at the discretion of their study specialist anaesthetist.

- Abdominal-perineal resections (APR) due to the greater area of dissection and skin
incision which will increase the level of baseline somatic pain felt by a patient.

- Requirement for postoperative drain in-situ, as this will drain the experimental
solution out of the abdomen.

- Preoperative systemic steroid dependence due to derangement of the inflammatory
response.

- Preoperative chronic pain illness including fibromyalgia, chronic regional pain
syndrome, chronic fatigue syndrome, non specific chronic pain requiring daily opiate
use, and history of alcohol or drug dependence due to the impact these have on
subjective interpretation of pain and tolerance to opioid requiring significantly
higher dosing regimens.

- Inability to consent or complete data scores in the study questionnaires due to
cognitive impairment and/or language barrier.

- Pregnancy or breastfeeding.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Current
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
4000 - Adelaide

Funding & Sponsors
Primary sponsor type
Other
Name
Royal Adelaide Hospital
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
University of Adelaide
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
University of South Australia
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Saint Andrew's Hospital
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Calvary North Adelaide Hospital
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the addition of a local anaesthetic infusion into the abdomen to
patient controlled analgesia in the management of postoperative pain and recovery after bowel
surgery. Half of the patients will have an infusion of a local anaesthetic called ropivacaine
and half will have an infusion of placebo in addition to their normal pain relief.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jaime A Duffield, BMBS PhD
Address 0 0
Royal Adelaide Hospital, Colorectal Surgical Unit Research Registrar
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries
Contact person responsible for updating information