|- candidate number||3929|
|- NTR Number||NTR1438|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||5-sep-2008|
|- Secondary IDs||MEC-2007-355 MAIV|
|- Public Title||Morphine vs. intravenous Acetaminophen after surgery in patients under the age of 1 year.|
|- Scientific Title||Morphine intravenous vs. Acetaminophen intravenous in neonates and young infants undergoing major, non-cardiac surgery.|
|- hypothesis||Patients after non-cardiac thoracic or abdominal major surgery receive morphine as pain relief medication whereas this is associated with morphine related side effects. In these patients a non-opioid drug could be appropriate for postoperative pain relief. Intermittent administration of intravenous acetaminophen, to young infants up to 48 hours after major surgery e.g. thoracic and abdominal, will lead to a clinically significant (>30%) morphine sparing effect. |
|- Healt Condition(s) or Problem(s) studied||Children, Opioids, Analgesics, Acetaminophen, Perfalgan, Post operative|
|- Inclusion criteria||1. Informed consent. |
2. Neonate / child under the age of one year.
3. Minimal post conceptual age of 36 weeks.
4. Minimal body weight of 1500 grams.
5. Major thoracic (non cardiac) or abdominal surgery, including urological surgery.
|- Exclusion criteria||1. Withdrawal of informed consent.|
2. Neonate/child with neurological, renal insufficiency, or hepatic dysfunction.
3. Chronic (more than one day) opioid or psychotropic drug (e.g. antiepileptics, benzodiazepines, antidepressants) exposure pre- or postnatal.
4. Opioid exposure <24 hrs before surgery.
5. Receiving ECMO-therapy.
6. Known allergy / intolerance for acetaminophen or morphine.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-mrt-2008|
|- planned closingdate||1-okt-2009|
|- Target number of participants||72|
|- Interventions||After surgery patients will be randomised for treatment with Morphine or Acetaminophen intravenoously. |
In case of post operative pain (COMFORT score>=17 and/or VAS>= 4) additional morphine in both groups is administrated following our post-operative pain protocol.
For PK-PD relationship for acetaminophen IV and morphine in this population three blood samples are taken from an indwelling arterial line and saliva cortisol is obtained.
|- Primary outcome||- The absolute amount of morphine in mcg/kg/48 hours is the primary outcome measure.
|- Secondary outcome||Secondary Objective(s): |
1. To compare in the first 48 hrs after abdominal or non-cardiac thoracic surgery in infants less than one year of age who receive either acetaminophen IV boluses or morphine IV.
a. number of patients needing extra morphine boluses.
b. the incidence of opioid related adverse effects;
- Hypotension with the need for vaso- active medication or fluid boluses.
- Seizures without other demonstrable causes.
- Bradycardia other than due to or directly related to the disease or operation.
- Decreased gasto-intestinal motility or intestinal obstruction not directly related to the underlying diagnosis or operation and not previously existing, with the need for intervention.
c. average pain scores, AUEC of pain score and percentage of abnormal scores (comfort / VAS)
d. % of time patient is adequately pain free, based on pain scores.
e. body part activity scores using acceleration sensor as surrogate marker of pain and pain thresholds.
f. saliva cortisol levels (as surrogate marker of stress).
e. renal clearance of acetaminophen and glucuronidation and sulphate formation.
g. pharmacogenetic markers (e.g. CYP polymorphisms)
PK-PD relationship for acetaminophen IV and morphine in this population three blood samples are taken from an indwelling arterial line.
|- Timepoints||Patients are followed 48 hours post operatively or is ended after an earlier discharge.|
|- Trial web site||N/A|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES||Prof.Dr. D. Tibboel|
|- CONTACT for SCIENTIFIC QUERIES||Prof.Dr. D. Tibboel|
|- Sponsor/Initiator ||Erasmus Medical Center, Sophia Children's Hospital, Department of Pediatric Surgical Intensive Care|
(Source(s) of Monetary or Material Support)
|Erasmus Medical Center, Sophia Children's Hospital|
|- Brief summary||SUMMARY Morphine intravenous vs. Acetaminophen intravenous in neonates and young infants undergoing major non-cardiac surgery
Patients after non-cardiac thoracic or abdominal major surgery receive morphine as pain relief medication whereas this is associated with morphine related side effects. In these patients a non-opioid drug could be appropriate for postoperative pain relief. Intermittent administration of intravenous acetaminophen, to young infants up to 48 hours after major surgery e.g. thoracic and abdominal, will lead to a clinically significant (>30%) morphine sparing effect.
The aim of this study is to test the hypothesis that intravenous acetaminophen will reduce morphine requirements in postoperative infants significantly (>30%).
Single centre prospective, randomized double blind study.
Infants less than one year of age, who are admitted to the ICU after major thoracic (non-cardiac) or abdominal surgery.
Patients will be randomized to receive either intermittent intravenous acetaminophen or continuous morphine IV infusion up to 48 hrs after surgery, with additional morphine boluses as escape medication in both groups.
Main study parameters/endpoints:
Body weight corrected morphine dose needed in the first 48 hrs post surgery. Mean morphine dose needed will be 30% less in the infants receiving acetaminophen IV as compared to the patients who received only morphine
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Possible burden and risk of study participation is the risk of insufficient analgesia after surgery with acetaminophen IV. This risk is minimized by the provision in the protocol for the administration of additional morphine in case of insufficient analgesia.
Acetaminophen has been widely studied in children over all age ranges and is deemed safe in the population to be studied when administered in therapeutic doses.
Benefits of participation can be better observation of the patient in relation to his/her analgesia and more prompt response with additional morphine if necessary. Hence, we expect patients in the study to be more pain free than patients not participating in a pain trial.
Also, if acetaminophen indeed reduces the total morphine dose required, a reduction in adverse effects of morphine can be expected (less post operative vomiting, less respiratory depression).
The study can only be carried out in this population as results from adults or healthy children cannot be extrapolated to this group of patients (critically ill children), due to differences in age and the underlying disease, which are mainly life threatening congenital anomalies, resulting in differences in pharmacokinetics and pharmacodynamics of both drugs.
|- Main changes (audit trail)|
|- RECORD||5-sep-2008 - 13-nov-2010|