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    The EU Clinical Trials Register currently displays   44339   clinical trials with a EudraCT protocol, of which   7369   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2015-002209-12
    Sponsor's Protocol Code Number:ABR59689
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2017-04-12
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedNetherlands - Competent Authority
    A.2EudraCT number2015-002209-12
    A.3Full title of the trial
    Less opioids after major abdominal surgery in young infants using wound catheter infusion with local anesthetics: a randomized controlled trial.
    Is een wondcatheter met lokaal anesthetica opioid sparend bij baby's na buikchirurgie?
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Wound catheter infusion after abdominal surgery in baby's.
    Wondkatheter met lokaal anesthetica bij baby's na buikchirurgie.
    A.3.2Name or abbreviated title of the trial where available
    Wound catheter infusion after abdominal surgery in baby's
    A.4.1Sponsor's protocol code numberABR59689
    A.5.4Other Identifiers
    Name:NTR6130Number:Nederlands Trial Register (Dutch Trial Registry)
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorErasmus MC-Sophia Children's Hospital
    B.1.3.4CountryNetherlands
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportStichting Coolsingel
    B.4.2CountryNetherlands
    B.4.1Name of organisation providing supportStichting Erasmus Fonds Pijngeneeskunde
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationErasmus MC Sophia
    B.5.2Functional name of contact pointLonneke Staals
    B.5.3 Address:
    B.5.3.1Street AddressWytemaweg 80
    B.5.3.2Town/ cityRotterdam
    B.5.3.3Post code3015 CN
    B.5.3.4CountryNetherlands
    B.5.4Telephone number0031107036020
    B.5.6E-maill.staals@erasmusmc.nl
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name ropivacaine
    D.2.1.1.2Name of the Marketing Authorisation holderFresenius Kabi
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameropivacaine
    D.3.2Product code ropivacaine
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Children < 1 year of age undergoing major open abdominal surgery.
    E.1.1.1Medical condition in easily understood language
    Children < 1 year of age undergoing major open abdominal surgery.
    E.1.1.2Therapeutic area Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10021298
    E.1.2Term Ileal atresia
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10010526
    E.1.2Term Congenital large intestinal atresia
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10002120
    E.1.2Term Anal atresia
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10010626
    E.1.2Term Congenital small intestinal atresia
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10062022
    E.1.2Term Intestinal atresia
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10013812
    E.1.2Term Duodenal atresia
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10028210
    E.1.2Term Multiple gastrointestinal atresias
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    In this prospective, double-blind, randomized controlled trial, we investigate the hypothesis that regional anesthesia provided by WCI with ropivacaine will reduce pain postoperatively (as measured with COMFORT behavior scale and Numeric Rating Scale (NRS) Pain scores) and lead to a morphine-sparing effect of at least 30% after major abdominal surgery in infants < 1 year of age.
    In this investigation also plasma ropivacaine levels will be measured, during the phase of continuous infusion via the wound catheter, to determine if levels of ropivacaine remain below toxic thresholds.

    Primary Objective:
    The mean cumulative amount of morphine administered over 48 hours postoperatively, in mcg/kg, will be compared in both groups (R group and control group).

    E.2.2Secondary objectives of the trial
    1. Efficacy of treatment of postoperative pain
    • Number of patients needing extra morphine boluses (rescue), over 48 hours.
    • Total amount of morphine administered postoperatively, until removal of the wound catheter.
    • AUC 24 hours COMFORT-B score and NRS, and percentage of high pain scores (NRS ≥ 4 and COMFORT ≥ 17).
    2. Safety of the use of WCI with ropivacaine
    • Toxicity of local anesthetic:
    - hypotension
    - arrhythmia
    - convulsions
    • The incidence of adverse effects related to the wound catheter
    - accidental luxation of the wound catheter
    - infection
    - hematoma of the wound
    - delayed healing of the wound
    - wound dehiscence
    • Plasma concentrations of ropivacaine will be measured, to determine if plasma levels do not exceed toxic thresholds.
    2. Adverse events related to the use of opioids
    • Signs of respiratory depression:
    • Gastro-intestinal
    • Hemodynamic
    4. Other variables
    • Surgical stress score
    • The Parents’ Postoperative Pain Measure- Short Form
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    In order to be eligible to participate in this study, a subject must meet all of the following criteria:
    - Informed consent
    - Children < 1 year of age
    - Minimal post-conceptual age of 35 weeks
    - Minimal body weight of 1500 grams
    - Abdominal (open) surgery

    E.4Principal exclusion criteria
    A potential subject who meets any of the following criteria will be excluded from participation in this study:
    - Withdrawal of informed consent
    - Child with neurological disease, renal or hepatic dysfunction
    - Chronic (more than one day) opioid or psychotropic drug (e.g. antiepileptics, benzodiazepines, antidepressants) exposure pre- or postnatal, in neonates (maximum 28 days old) presenting for surgery, or < 1 month ago.
    - Opioid exposure <24 hours before surgery
    - Receiving ECMO therapy
    - Known allergy / intolerance for paracetamol or morphine
    - Contra-indications for regional analgesia techniques:
    o Allergy to local anesthetics
    o Local or general infection (sepsis)
    E.5 End points
    E.5.1Primary end point(s)
    Primary outcome measure is mean cumulative morphine dose over 48 hours in mcg/kg.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Children will be randomized for treatment with wound catheter infusion (WCI) with a bolus dose and continuous infusion with ropivacaine (R group) or with placebo (saline) (C). At the end of surgery both groups receive a bolus dose IV: morphine in the C group and placebo (saline) in the R group. Both groups will receive intermittent administration of paracetamol IV (as primary analgesic) and titrated morphine IV in case of documented pain as rescue therapy.
    The child's postoeprative pain is assessed every 2 hours, using the validated COMFORT behavior scale and the Numeric Rating Scale Pain (assessed by the attending nurse). Additional morphine is administered whenever the NRS > 4 and COMFORT B scale > 16, which indicates pain.
    E.5.2Secondary end point(s)
    1. Number of patients needing extra morphine boluses (rescue), over 48 hours.
    2. Total amount of morphine administered postoperatively, until removal of the wound catheter.
    3. AUC 24 hours COMFORT-B score and NRS, and percentage of high pain scores.
    4. The incidence of opioid related adverse effects:
    - Signs of respiratory depression
    - Gastro-intestinal
    - Hemodynamic
    5. The incidence of ropivacaine related side effects
    6. The incidence of adverse effects related to the wound catheter:
    - Accidental luxation of the wound catheter
    - Infection: wound infection, sepsis
    - Hematoma of the wound
    - Delayed healing of the wound
    - Wound dehiscence
    7. Plasma concentrations of ropivacaine:
    To determine the PK-PD relationship for paracetamol IV and morphine IV, and to
    determine if plasma ropivacaine levels do not exceed toxic levels, blood samples will be
    taken from an indwelling arterial line, or at the same time a regular blood sample is taken
    by heel prick, concomitant with blood sampling for clinical purposes (in case there is no
    arterial line). PK and PD data will be fitted using data from all individuals simultaneously
    using non-linear mixed effect modelling (NONMEM). Patients will not suffer extra heel
    pricks for only study purposes. With respect to the ethical requirement that not more
    than 3% of the total blood volume (80-100 ml/kg) can be drawn from a patient, sampling
    will be restricted to maximum three samples per day (0.5 ml each) (maximum six samples
    over the whole study period).

    Other study parameters
    1. Baseline value: post conceptual (PC) age at birth, birth weight, (PC) age at the day of operation, weight at the day of operation, indication for surgery, type of operation, medication use, concomitant disease, ASA classification.
    2. Time until discharge from the PICU/ recovery ward
    3. Surgical stress:
    To classify the surgical stress of the different procedures, the Surgical Stress Score is computed by the surgeon at the end of surgery:
    the amount of blood loss (score range 0-3)
    site of surgery (score range 0-2)
    amount of superficial trauma (score range 1-3)
    extent of visceral trauma (score range 1-4)
    duration of surgery (score range 1-5)
    associated stress factors
    hypothermia (score range 0-3)
    infection (score range 0-3)
    The total scores are used to divide the procedures in minor, moderate or severe surgical stress.
    4. PPPM-SF: Parents’ Postoperative Pain Measure – Short Form
    One week after the operation, the parents are contacted by telephone to fill out the PPPM-SF, a validated questionnaire, which shows the postoperative recovery of a child after discharge from the hospital.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Number of patients needing extra morphine boluses (rescue), over 48 hours.
    2. Total amount of morphine administered postoperatively, until removal of the wound catheter (until 72 hours postop)
    3. AUC 24 hours COMFORT-B score and NRS, and percentage of high pain scores.
    4. The incidence of opioid related adverse effects: until 72 hours postop
    5. The incidence of ropivacaine related side effects: until 72 hours postop
    6. The incidence of adverse effects related to the wound catheter: until 72 hours postop
    7. Plasma concentrations of ropivacaine: maximum six samples over 72 hours
    8. Baseline values: at inclusion
    9. Time until discharge from the PICU/ recovery ward: at discharge
    10. Surgical stress: postoperatively
    11. PPPM-SF: One week after the operation
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The study will be temporarily terminated when a patients shows signs of clinical toxicity of local anesthetics, or when a serious adverse event, possibly related to the wound catheter or ropivacaine, occurs (SUSAR).
    In this case the Data Safety Monitoring Board (DSMB), will do an interim analysis, including analysis of the results of the plasma concentrations of ropivacaine per patient, and they will advise on the complete termination of the study, or if the investigation can proceed.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 60
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Yes
    F.1.1.2.1Number of subjects for this age range: 60
    F.1.1.3Newborns (0-27 days) Yes
    F.1.1.3.1Number of subjects for this age range: 60
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 60
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Potential participants will be infants less than 1 year of age, who are undergoing major abdominal surgery (not laparoscopic). Sixty children (30 in each group) will be included in this investigation.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state60
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    The included patient will receive normal postoperative care, not different from the expected normal treatment of their condition
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-04-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-06-21
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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