Child, OnlyPhase 4NCT03994146
Remifentanil Tapering and Post-adenotonsillectomy Pain in Children
A Phase 4 study testing Remifentanil and Sodium Chloride 9mg/mL in people with Child, Only and Pain, run by University Hospital, Akershus at 2 sites in Norway.
Trial summary
Tonsillectomy is the commonest operation of childhood and results in considerable pain. Remifentanil is a potent, ultra short acting opioid with a long- established safety record in paediatric anaesthesia that is used to provide intraoperative analgesia. Read more about this study
- Who is it for?
- Ages 1 year to 10 yearsHealthy volunteers can take part
- Conditions the study is for
- Child, Only, Pain, Tonsillectomy
- What is being tested?
- Remifentanil and Sodium Chloride 9mg/mL
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 2 sitesNorway
- Study dates
- 16 Jan 2020to 18 Aug 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 10 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- American Society Anaesthesiology I-II children 1 to 10 years
- Weight over 10.0 Kg
- Presenting for tonsillotomy / tonsillectomy or adenotonsillectomy at Akershus Universitetssykehus, Lørenskog and Lovisenberg Diakonale Hospital, Norway
Who cannot join
- Children who have had airway surgery previously.
- Children who have had any type of surgery in the previous 12 months.
- Children using chronic pain medication or who have used analgesia in the 24 hours preceding surgery.
- Children who are known to suffer from NSAID sensitive asthma.
- Children with a known allergy to propofol or remifentanil.
- Pre-existing cardiac, renal, liver dysfunction.
- Children or parents who are not fluent in Norwegian or English.
- Children in whom more than three attempts at intravenous cannulation are required or in those who request an inhalational induction or premedication
Trial locations and contacts
2 sites in 1 country.
Norway2 sites
Akershsus Universitetssykehus
Lørenskog, Akershus, 1478
Lovisenberg Diakonale Sykehus
Oslo, 0456
About this study
Official title: Remifentanil Tapering and Post-adenotonsillectomy Pain in Children: a Randomised, Placebo Controlled, Double Blind Study
Tonsillectomy is the commonest operation of childhood and results in considerable pain.
Remifentanil is a potent, ultra short acting opioid with a long- established safety record in paediatric anaesthesia that is used to provide intraoperative analgesia.
Read more
There is evidence from adult studies that remifentanil increases postoperative pain, although this may be ablated if propofol (rather than inhalational anaesthesia) is used or if the remifentanil is tapered rather than abruptly discontinued at the end of surgery.
The analgesic effect of gradual withdrawal of remifentanil at the end of surgery has not been studied in children and may have significant clinical implications.
The primary measure of efficacy will be the dose of fentanyl rescue analgesia in the peri-operative period (1 mcg.kg-1 bolus for >20% increase in pulse, blood pressure or movement intraoperatively or a FLACC(Face, Legs, Arms, Cry, Consolablity) score of >5 in recovery).
Read the detailed description
Tonsillectomy is one of the commonest childhood operations in the world; approximately 9200 children have their tonsils removed every year in Norway alone.
Postoperative pain following the procedure is significant and notoriously difficult to mange. It´s management is potentially complicated by nausea and the risk of tonsillar infection or re-bleeding. Post-tonsillectomy pain in children is persistent, with 75% of children experiencing significant pain for the first three days and 50% still suffering with significant pain one week after the procedure. As well as delaying recovery, reducing oral intake of food and drink and disturbing sleep, post tonsillectomy pain has been shown to result in more than 50% of patients and their parents consulting their primary care physician in the post operative period, with the ensuing costs to the families and healthcare providers.
It is worth noting, that despite significant postoperative pain and potential complications, recovery after adeno / tonsillectomy is excellent.
The operative nature of tonsillectomy and adenotonsillectomy necessitates the provision of general anaesthesia to the child. The technique must ensure sufficient depth of anaesthesia and analgesia and protection of the airway from blood and surgical debris. Whilst there are a wide variety of anaesthetic techniques employed to achieve these goals,Total Intra Venous Anaesthesia (TIVA) with propofol and remifentanil has been shown in previous studies to be superior to volatile based (gas) anaesthesia, resulting in less post operative nausea and vomiting, less long term adverse behavioural changes, improved quality of emergence from anaesthesia, and less environmental pollution.
The use of remifentanil and propofol TIVA in children is well established and has been in use since at least the year 2000 for children undergoing tonsillectomy. Despite this the effects of remifentanil dosing on post-operative pain has not been studied in children undergoing tonsillectomy, though it may play a significant role.
- Conditions
- Child, Only, Pain, Tonsillectomy, Remifentanil
- Being tested
- Remifentanil, Sodium Chloride 9mg/mL
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RemifentanilDrug
Also called Ultiva
Syringe containing 40 ml of Remifentanil 50 µg/ml for intravenous administration.
In order to maintain double blinding two identical syringes, prepared by pharmacy according to randomisation, will be simultaneously infused. One of the syringes will be abruptly stopped at the end of the operation whilst the other is tapered by stepwise decreases in infusion rate prior to the end of surgery.
Sodium Chloride 9mg/mLDrug
Also called Normal saline, Placebo
Syringe containing 40 ml of Sodium Chloride 9 mg/ml for intravenous administration.
In order to maintain double blinding two identical syringes, prepared by pharmacy according to randomisation, will be simultaneously infused. One of the syringes will be abruptly stopped at the end of the operation whilst the other is tapered by stepwise decreases in infusion rate prior to the end of surgery.
| Study group | Role | What they receive |
|---|---|---|
| Remifentanil tapering / Placebo abrupt cessation | Experimental | Syringe one contains Remifentanil 2 mg in 40 ml NaCl 9 mg.ml-1 = 50 µg.ml-1 which will be infused at a rate of 0.9 µg.kg-1.min-1 and Syringe two contains 40 ml NaCl 9 mg.ml-1 at an identical infusion rate. According to randomisation syringe one will then be tapered towards the end of surgery and syringe two abruptly stopped. Receives: Drug: Remifentanil; Drug: Sodium Chloride 9mg/mL |
| Placebo tapering / Remifentanil abrupt cessation. | Placebo comparator | Syringe one contains 40 ml NaCl 9 mg.ml-1 and Syringe two contains Remifentanil 2 mg in 40 ml NaCl 9 mg.ml-1 = 50 µg.ml-1 which will be infused at a rate of 0.9 µg.kg-1.min-1. According to randomization syringe one will be tapered towards the end of surgery and syringe two abruptly stopped. Receives: Drug: Remifentanil; Drug: Sodium Chloride 9mg/mL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intravenous fentanyl consumption in the perioperative period (mcg/kg).
Intravenous fentanyl consumption in the perioperative period (mcg/kg).
Measured: From the induction of anaesthesia until discharge from the day case surgical unit.4 hours.
Secondary outcomes (2)
Faces Legs Activity Cry Consolability (FLACC) pain scores at 20,40,60,90 and 120 minutes after the operation to give a Sum of Pain Intensity Differences (SPID).
The Face, Legs, Activity, Cry, Consolability scale or FLACC scale is a well validated measurement used to assess pain for children or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 0 representing no pain. The scale has five criteria, which are each assigned a score of 0, 1 or 2.
Thus the face component is scored as 0 for no particular expression or smile, 1 for an occasional grimace and 2 for a constant quivering chin or clenched jaw.
The 0-2 score from each of the 5 domains is summated to give a total score between 0 and 10.
A lower pain score indicates a better outcome than a high pain score.
Measured: From cessation of anaesthesia until 120 minutes after the cessation of anaesthesia.
Parents' Post Operative Pain Measure (PPOMP) on post operative days 1,3,7,10,14 and 28
The Parents' Post Operative Pain Measure (PPOMP) is a well validated 15 point questionnaire used to measure childrens' pain after moderately or severely painful procedures.
The parents are asked to complete the survey between particular times each day (e.g between supper and bed time). The questionnaire consists of 15 YES / NO questions such as: "When your child was recovering from surgery between supper and bed time today did s/he...
Cry more easily than usual ? YES / NO
Refuse to eat? YES/ NO
Want to be closer to you than usual? YES / NO.
The YES response are scored as 1 and the NO responses scores as 0. The sum score ranges from 0 to 15.
A lower pain score indicates a better outcome than a high pain score.
Measured: From the cessation of anaesthesia until the 28th day following discharge from the day case surgical unit.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2019
- Study start16 Jan 2020
- Primary completion18 Aug 2023
- Study completion18 Aug 2023
Why it stopped: Recruitment rate was not compatible with study completion
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Child, OnlyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double blind, randomised, placebo controlled trial.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Akershus
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, William James Morton, University Hospital, Akershus
- Investigators
- Signe Søvik, MD. PhD, Principal investigator, University Hospital, Akershus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03994146
- Sponsor's protocol ID
- 2019-001677-81
- Other IDs
- 2019
- Status last verified
- Aug 2023
- First submitted
- 13 Jun 2019
- Last updated
- 22 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: On request and following consultation with the Regional Ethics Committee and the Data Protection Officer at the host institution.
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Remifentanil Tapering and Post-adenotonsillectomy Pain in Children: a Randomised, Placebo Controlled, Double Blind Study
- ClinicalTrials.gov ID
- NCT03994146
- Acronym / sponsor ID
- 2019-001677-81
- Conditions
- Child, Only, Pain, Tonsillectomy, Remifentanil
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment rate was not compatible with study completion
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University Hospital, AkershusUniversity, hospital or other
- Study start
- 16 Jan 2020 (actual)
- Primary completion
- 18 Aug 2023 (actual)
- Study completion
- 18 Aug 2023 (actual)
- First posted
- 21 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Tonsillectomy is the commonest operation of childhood and results in considerable pain.
Remifentanil is a potent, ultra short acting opioid with a long- established safety record in paediatric anaesthesia that is used to provide intraoperative analgesia.
There is evidence from adult studies that remifentanil increases postoperative pain, although this may be ablated if propofol (rather than inhalational anaesthesia) is used or if the remifentanil is tapered rather than abruptly discontinued at the end of surgery.
The analgesic effect of gradual withdrawal of remifentanil at the end of surgery has not been studied in children and may have significant clinical implications.
The primary measure of efficacy will be the dose of fentanyl rescue analgesia in the peri-operative period (1 mcg.kg-1 bolus for >20% increase in pulse, blood pressure or movement intraoperatively or a FLACC(Face, Legs, Arms, Cry, Consolablity) score of >5 in recovery).
Detailed description
Tonsillectomy is one of the commonest childhood operations in the world; approximately 9200 children have their tonsils removed every year in Norway alone.
Postoperative pain following the procedure is significant and notoriously difficult to mange. It´s management is potentially complicated by nausea and the risk of tonsillar infection or re-bleeding. Post-tonsillectomy pain in children is persistent, with 75% of children experiencing significant pain for the first three days and 50% still suffering with significant pain one week after the procedure. As well as delaying recovery, reducing oral intake of food and drink and disturbing sleep, post tonsillectomy pain has been shown to result in more than 50% of patients and their parents consulting their primary care physician in the post operative period, with the ensuing costs to the families and healthcare providers.
It is worth noting, that despite significant postoperative pain and potential complications, recovery after adeno / tonsillectomy is excellent.
The operative nature of tonsillectomy and adenotonsillectomy necessitates the provision of general anaesthesia to the child. The technique must ensure sufficient depth of anaesthesia and analgesia and protection of the airway from blood and surgical debris. Whilst there are a wide variety of anaesthetic techniques employed to achieve these goals,Total Intra Venous Anaesthesia (TIVA) with propofol and remifentanil has been shown in previous studies to be superior to volatile based (gas) anaesthesia, resulting in less post operative nausea and vomiting, less long term adverse behavioural changes, improved quality of emergence from anaesthesia, and less environmental pollution.
The use of remifentanil and propofol TIVA in children is well established and has been in use since at least the year 2000 for children undergoing tonsillectomy. Despite this the effects of remifentanil dosing on post-operative pain has not been studied in children undergoing tonsillectomy, though it may play a significant role.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double blind, randomised, placebo controlled trial.
| Arm | Type | Receives |
|---|---|---|
| Remifentanil tapering / Placebo abrupt cessation | Experimental | Drug: Remifentanil, Drug: Sodium Chloride 9mg/mLSyringe one contains Remifentanil 2 mg in 40 ml NaCl 9 mg.ml-1 = 50 µg.ml-1 which will be infused at a rate of 0.9 µg.kg-1.min-1 and Syringe two contains 40 ml NaCl 9 mg.ml-1 at an identical infusion rate. According to randomisation syringe one will then be tapered towards the end of surgery and syringe two abruptly stopped. |
| Placebo tapering / Remifentanil abrupt cessation. | Placebo comparator | Drug: Remifentanil, Drug: Sodium Chloride 9mg/mLSyringe one contains 40 ml NaCl 9 mg.ml-1 and Syringe two contains Remifentanil 2 mg in 40 ml NaCl 9 mg.ml-1 = 50 µg.ml-1 which will be infused at a rate of 0.9 µg.kg-1.min-1. According to randomization syringe one will be tapered towards the end of surgery and syringe two abruptly stopped. |
Who may qualify
- Ages
- 1 year to 10 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- American Society Anaesthesiology I-II children 1 to 10 years
- Weight over 10.0 Kg
- Presenting for tonsillotomy / tonsillectomy or adenotonsillectomy at Akershus Universitetssykehus, Lørenskog and Lovisenberg Diakonale Hospital, Norway
Key exclusion criteria (8 listed)
- Children who have had airway surgery previously.
- Children who have had any type of surgery in the previous 12 months.
- Children using chronic pain medication or who have used analgesia in the 24 hours preceding surgery.
- Children who are known to suffer from NSAID sensitive asthma.
- Children with a known allergy to propofol or remifentanil.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RemifentanilAlso: UltivaSyringe containing 40 ml of Remifentanil 50 µg/ml for intravenous administration. In order to maintain double blinding two identical syringes, prepared by pharmacy according to randomisation, will be simultaneously infused. One of the syringes will be abruptly stopped at the end of the operation whilst the other is tapered by stepwise decreases in infusion rate prior to the end of surgery. | Drug | Placebo tapering / Remifentanil abrupt cessation., Remifentanil tapering / Placebo abrupt cessation |
| Sodium Chloride 9mg/mLAlso: Normal saline, PlaceboSyringe containing 40 ml of Sodium Chloride 9 mg/ml for intravenous administration. In order to maintain double blinding two identical syringes, prepared by pharmacy according to randomisation, will be simultaneously infused. One of the syringes will be abruptly stopped at the end of the operation whilst the other is tapered by stepwise decreases in infusion rate prior to the end of surgery. | Drug | Placebo tapering / Remifentanil abrupt cessation., Remifentanil tapering / Placebo abrupt cessation |
Primary outcome
Intravenous fentanyl consumption in the perioperative period (mcg/kg).
Time frame: From the induction of anaesthesia until discharge from the day case surgical unit.4 hours.
Intravenous fentanyl consumption in the perioperative period (mcg/kg).
2 secondary outcomes
Faces Legs Activity Cry Consolability (FLACC) pain scores at 20,40,60,90 and 120 minutes after the operation to give a Sum of Pain Intensity Differences (SPID).
Time frame: From cessation of anaesthesia until 120 minutes after the cessation of anaesthesia.
Parents' Post Operative Pain Measure (PPOMP) on post operative days 1,3,7,10,14 and 28
Time frame: From the cessation of anaesthesia until the 28th day following discharge from the day case surgical unit.
Results and safety
The study was stopped early (reason given: Recruitment rate was not compatible with study completion). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2023.
- Individual participant dataSharing planned: Yes. On request and following consultation with the Regional Ethics Committee and the Data Protection Officer at the host institution.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Signe Søvik, MD. PhD principal investigator
University Hospital, Akershus
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Remifentanil and Sodium Chloride 9mg/mL in people with Child, Only and Pain, run by University Hospital, Akershus at 2 sites in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Recruitment rate was not compatible with study completion). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intravenous fentanyl consumption in the perioperative period (mcg/kg). (time frame: From the induction of anaesthesia until discharge from the day case surgical unit.4 hours.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2023.