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Trial registered on ANZCTR


Registration number
ACTRN12622000489796
Ethics application status
Approved
Date submitted
17/10/2021
Date registered
28/03/2022
Date last updated
8/03/2023
Date data sharing statement initially provided
28/03/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Wound catheters as an alternative to morphine after major surgery in newborn infants: A comparative study.
Scientific title
The effect of conventional intravenous therapy compared to subcutaneous wound catheter infusion with local anesthetic for the management of postoperative pain in neonates undergoing major surgery.
Secondary ID [1] 305296 0
Eudra CT nr: 2014-004701-32
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Postoperative pain 323611 0
Condition category
Condition code
Anaesthesiology 321147 321147 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
WCI (Wound catheter infusion group)
Wound catheter 19 G PainBuster®, Amaro, Italy; length 2.5 or 6.5 cm.
The wound catheter is put into place before skin closure by the paediatric surgeon at the end of surgery.
Bolus dose levo-bupivacaine (AbbVie AB, 1,25 mg/ml). Immediately after skin closure a bolus dose of levo-bupivacaine 0.5 mg/kg is administered through the wound catheter.
Postoperative continuous infusion levo-bupivacaine (AbbVie AB, 1,25 mg/ml). At arrival to the PICU a continuous infusion of levo-bupivacaine is started at a rate of 0.2 mg/kg/h, using an infusion pump (Perfusor® Space, B Braun, Melsungen AG, Germany).

The study period (IVPT/WCI) will continue for 72 hours. The WCI catheter is thereafter removed by independent personnel. If pain treatment still is required clinical routine is followed.

Coexistent pain therapy - Concomitant medication, both IVPT and WCI
Paracetamol: According to clinical routine ALL study patients (IVPT and WCI group) will have a prescription of paracetamol (Fresenius Kabi, 10 mg/ml) delivered intravenously 4 times per day (7,5-15 mg/kg).
Rescue dose: A “rescue” dose of intravenous administered morphine (Morfin meda, 1 mg/ml) will be prescribed (25-50 microg/kg) to be administered if pain scores indicate pain (Comfort-B), A special protocol is used for this.
Further, a “rescue” dose of intravenous administered clonidine (Boehringer Ingelheim International GmbH, 15 microg/ml) will be prescribed (0,5-1 microg/kg) to be administered if pain scores indicate pain.
Other drugs: In this study there are no limitations concerning other drugs, such as antibiotics, diuretics etc.

Intervention code [1] 321706 0
Treatment: Drugs
Intervention code [2] 321707 0
Treatment: Other
Comparator / control treatment
Conventional pain treatment with intravenous drugs.
IVPT (Intravenous pain therapy group)
Morphine: Continuous infusion with morphine (Morfin Meda, 10 mg/ml). Infusion rate 10 microgram/kg/h.Started when the patient arrives at PICU directly after surgery. The strength of the solution will wary depending on the patient’s body weight.
Clonidine: Continuous infusion of clonidine (Boehringer Ingelheim International GmbH, 2,5 mikrog/ml).Started when the patient arrives at PICU directly after surgery. Infusion rate 1 microg/kg/h.
Coexistent pain therapy - Concomitant medication, both IVPT and WCI
Paracetamol: According to clinical routine ALL study patients (IVPT and WCI group) will have a prescription of paracetamol (Fresenius Kabi, 10 mg/ml) delivered intravenously 4 times per day (7,5-15 mg/kg).
Rescue dose: A “rescue” dose of intravenous administered morphine (Morfin meda, 1 mg/ml) will be prescribed (25-50 microg/kg) to be administered if pain scores indicate pain (Comfort-B), A special protocol is used for this.
Further, a “rescue” dose of intravenous administered clonidine (Boehringer Ingelheim International GmbH, 15 microg/ml) will be prescribed (0,5-1 microg/kg) to be administered if pain scores indicate pain.
Control group
Active

Outcomes
Primary outcome [1] 328934 0
Multimodal postoperative pain documentation and comparison for the two methods used during the study period. Pain assessment will be documented every second hour using the Comfort-B scale

Timepoint [1] 328934 0
Pharmacodynamic data will be presented as pain scores at 24, 48 and 72 (primary time-point) hours postoperatively.
Primary outcome [2] 330221 0
Total opioid consumption
Opioid consumption will be recorded and documented each 24 hours.
Timepoint [2] 330221 0
24, 48 and 72 (primary time-point) hours postoperatively.
Secondary outcome [1] 400893 0
Wound assessments: The wound will be inspected daily until postoperative day 10 and at follow up visit. The following items are specially noted: leakage at wound site, presence of erythema around the wound, signs of infection and presence of normal wound healing at postoperative day 10.
Timepoint [1] 400893 0
The wound will be inspected daily until postoperative day 10 and at follow up visit 1-2 months postoperatively.
Secondary outcome [2] 400894 0
Time to successful enteral feeding.

Enteral feeding is deemed successful if not resulting in gastric retention or vomiting. The time to first successful full meal will be noted into study protocol.
Assessed by accessing patient medical record.
Timepoint [2] 400894 0
Time of discharge from the hospital
Secondary outcome [3] 400895 0
Time to endotracheal extubation will be recorded.
Timepoint [3] 400895 0
Time of discharge from Pediatric Intensive Care Unit (PICU)
Secondary outcome [4] 405334 0
Pharmacokinetic data presented as total and free concentration of levobupivacaine.
Serum samples.
Timepoint [4] 405334 0
12,24,48 and 72 hours postoperatively.
Secondary outcome [5] 407393 0
Pharmacokinetic data on Alpha 1-acid-glycoprotein (AAGP)
Serum samples
Timepoint [5] 407393 0
Peroperatively and 72 hours postoperatively.
Secondary outcome [6] 407396 0
Signs of LAST (local anesthesia toxicity)
Arytmia
Seizures
Timepoint [6] 407396 0
ECG continuous during 72 hours.
EEG if suspected during 72 hours

Eligibility
Key inclusion criteria
Less than 3 month of age
Full term (>gestational week 36+6)
Scheduled for major abdominal or thoracic surgery
Approved and documented written and oral consent from both parents
Minimum age
No limit
Maximum age
3 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Absence of parental consent
Allergy to local anesthetics
Known or suspected liver-, kidney dysfunction or neurological disorder associated with peripheral nerve damage.
Intraperitoneal infection/sepsis.
Reoperation within 6 weeks.
Infants with another severe coexisting sickness (>ASAIII)
Coagulation disorder.
Protocol violation.

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 randomization by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomization table created by computer software.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
All statistical tests are estimated with a two-sided confidence interval. Assuming 15 and 45
observations respectively, in combination with a success rate of 100%, the 95% confidence interval
would be 81.9 to 100% and 93.6 to100% respectively.
We decided to include 30 subjects in the study.


Data will be analysed using non parametrical statistical methods.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
12/01/2021
Date of last participant enrolment
Anticipated
31/12/2023
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
30
Accrual to date
2
Final
Recruitment outside Australia
Country [1] 24115 0
Sweden
State/province [1] 24115 0
Stockholm

Funding & Sponsors
Funding source category [1] 309669 0
Hospital
Name [1] 309669 0
Karolinska University Hospital
Country [1] 309669 0
Sweden
Primary sponsor type
Hospital
Name
Karolinska University Hospital , Region Stockholm
Address
Karolinska University Hospital
Eugeniavägen 23
171 64 Stockholm
Country
Sweden
Secondary sponsor category [1] 310687 0
Charities/Societies/Foundations
Name [1] 310687 0
H.K.H kronprinsessan Lovisas förening
Address [1] 310687 0
Scheelegatan 12
112 28
Stockholm
Country [1] 310687 0
Sweden
Secondary sponsor category [2] 310743 0
Charities/Societies/Foundations
Name [2] 310743 0
Fredrik och Ingrid Thurings stiftelse
Address [2] 310743 0
SEB. Stiftelser KGS
106 40 Stockholm
Country [2] 310743 0
Sweden

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309437 0
Regional Ethics committee Uppsala
Ethics committee address [1] 309437 0
Box 2110
75002 Uppsala
Ethics committee country [1] 309437 0
Sweden
Date submitted for ethics approval [1] 309437 0
03/09/2019
Approval date [1] 309437 0
13/05/2020
Ethics approval number [1] 309437 0

Summary
Brief summary
We have in our group together with our colleagues at the paediatric anaesthesia department and neonatal department since over a decade had a great interest in finding local anaesthesia methods that even our most immature patients can take advantage of.
The Primary aim of this study is to demonstrate that Wound catheter infusion (WCI) with local anaesthetics is at least as effective as Intravenous pain therapy( IVPT) regarding postoperative pain treatment after major thoracic or abdominal surgery in neonates.
Secondary aims are to document effectiveness and safety of conventional intravenously pain treatment therapy (IVPT) and WCI after major thoracic or abdominal surgery in neonate as well as comparing wound healing in the two groups.
In this prospective randomized study, a total of 30 full term infants, less than 3 months of age and scheduled for major abdominal or thoracic surgery will be included. After enrolment patients will be randomly assigned to receive either intravenous pain therapy or wound catheter infusion with levobupivacaine for postoperative pain treatment. Data collection will start postoperatively in the PICU. Pharmacokinetic and pharmacodynamic data will be collected for 72 hours. The surgical wound healing process will be monitored for 10 days and later at follow up. Pain intensity will be analysed and compared in the two groups.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 114154 0
Dr Marie Anell Olofsson
Address 114154 0
Karolinska University Hospital
Eugeniavägen 23
BIVA F3:66
171 64 Stockholm
Country 114154 0
Sweden
Phone 114154 0
+468517772690
Fax 114154 0
Email 114154 0
marie.anell-olofsson@regionstockholm.se
Contact person for public queries
Name 114155 0
Dr Marie Anell Olofsson
Address 114155 0
Karolinska University Hospital
Eugeniavägen 23
BIVA F3:66
171 64 Stockholm
Country 114155 0
Sweden
Phone 114155 0
+468517772690
Fax 114155 0
Email 114155 0
marie.anell-olofsson@regionstockholm.se
Contact person for scientific queries
Name 114156 0
Dr Marie Anell Olofsson
Address 114156 0
Karolinska University Hospital
Eugeniavägen 23
BIVA F3:66
171 64 Stockholm
Country 114156 0
Sweden
Phone 114156 0
+468517772690
Fax 114156 0
Email 114156 0
marie.anell-olofsson@regionstockholm.se

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This is a very small material of infants that is included.
There is a possibility to identify the participants and they are not able to give their own consent to this.


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
No additional documents have been identified.