Postoperative PainNCT03908060
Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Laparoscopic Hysterectomy
A study testing Methadone and Morphine in people with Postoperative Pain, run by University of Aarhus at 1 site in Denmark.
Trial summary
The role of a single-dose of intraoperative methadone on postoperative pain and opioid consumption in patients undergoing hysterectomy remains scarcely explored. A prospective double-blind, randomised controlled trial investigating the effect of a single-dose of intraoperative methadone in patients scheduled for same… Read more about this study
- Who is it for?
- Ages 18 to 110 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Postoperative Pain
- What is being tested?
- Methadone and Morphine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 126 participants
- Where
- 1 siteDenmark
- Study dates
- 6 May 2019to 1 Dec 2022
- Phase
- Interventional
- 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 18 to 110 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients scheduled for elective laparoscopic hysterectomy for benign indications
Who cannot join
- American Society of Anaesthesiologists (ASA) physical status IV or V
- prolonged QT-interval assessed by electrocardiogram (> 440 milliseconds)
- Existing treatment with medications prolonging the QT-interval
- Hysterectomy due to malignancy or acute bleeding disorders
- Allergy to study drugs
- Preoperative daily use of opioids
Show all 17Show fewer
- Severe respiratory insufficiency
- Heart failure
- Acute alcohol intoxication/delirium tremens
- Increased intracranial pressure
- Acute liver disease
- Acute abdominal pain
- Liver insufficiency
- Kidney insufficiency
- Treatment with rifampicin
- Breastfeeding
- Inability to provide informed consent.
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Anaesthesiology and Intensive Care, Horsens Regional Hospital
Horsens, Central Jutland, 8700
About this study
Official title: Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Laparoscopic Hysterectomy: a Prospective, Double-blind, Randomised Controlled Trial
The role of a single-dose of intraoperative methadone on postoperative pain and opioid consumption in patients undergoing hysterectomy remains scarcely explored. A prospective double-blind, randomised controlled trial investigating the effect of a single-dose of intraoperative methadone in patients scheduled for same day hysterectomy is therefore conducted.
Read the detailed description
Background with aim: Hysterectomy is the most common major gynaecological procedure in the world and hysterectomy on benign indications are increasingly being performed as same-day surgery. Therefore, perioperative anaesthesia has moved towards the use of very short-acting opioids with the incitement to speed up extubation and facilitate hospital discharge. However, the potential consequence is that more patients experience pain and discomfort.
Methadone has several desirable pharmacological features, and a single intraoperative dose of the long acting opioid could therefore theoretically expand the analgesic window and reduce postoperative opioid consumption compared to the more conventional use of short-acting opioids. The aim of this study is to investigate the effect of a single-dose of intravenous intraoperative methadone on postoperative opioid consumption, pain and side effects in patients scheduled for hysterectomy for benign indications. Our primary hypothesis is that intravenous perioperative methadone reduces opioid consumption (oral cumulative equivalent dose) by 30% during the first 24 postoperative hours compared to intravenous morphine.
Methods: 126 patients will be included in an investigator-initiated, prospective, randomised, double-blind, controlled trial with two arms: an intervention arm (methadone 0.2 mg/kg ideal body weight) and a control arm (morphine 0.2 mg/kg ideal body weight). The study will be GCP-monitored, and is approved by the Danish Health and Medicines Authority (2018-004351-20) and the Central Denmark Region Committees on Health Research Ethics (1-10-72-365-18).
Hypothesis: The results will probably be applicable to other types of surgery involving visceral pain, and thus the present study has the potential to improve the pain management for a large number of patients undergoing surgery.
- Conditions
- Postoperative Pain
- Being tested
- Methadone, Morphine
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethadoneDrug
One intravenous administration of methadone (0.2 mg/kg ideal body weight)
MorphineDrug
One intravenous administration of morphine (0.2 mg/kg ideal body weight)
| Study group | Role | What they receive |
|---|---|---|
| Intravenous single-dose methadone | Experimental | A 10 ml syringe with 2 mg/ml of methadone will be prepared and and study drug will be administered as intravenous bolus dose (0.2 mg/kg) corresponding to 1 ml for every 10 kg of ideal body weight (height (cm) - 105). Receives: Drug: Methadone |
| Intravenous single-dose morphine | Active comparator | A 10 ml syringe with 2 mg/ml of morphine will be prepared and study drug will be administered as intravenous bolus dose (0.2 mg/kg) corresponding to 1 ml for every 10 kg of ideal body weight (height (cm) - 105). Receives: Drug: Morphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Opioid consumption at 24 hours after extubation (cumulative opioid consumption)
cumulative opioid consumption in oral morphine equivalents
Measured: 24 hours
Opioid consumption at 6 hours after extubation (cumulative opioid consumption)
cumulative opioid consumption in oral morphine equivalents
Measured: 6 hours
Secondary outcomes (2)
Pain intensity (NRS, 0-10) at rest and coughing
Numeric Rating Scale (NRS) ranging from 0 (no pain) to 10 (worst imaginable pain)
Measured: 0-48 hours after extubation
Postoperative side effects/ adverse events (nausea and vomiting, sedation, hypoventilation, and hypoxemia)
Number of patients
Measured: 0-72 hours after extubation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2019
- Study start6 May 2019
- Primary completion8 Jul 2022
- Study completion1 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Postoperative PainStudies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 126 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kristian Friesgaard, MD, PhD, Principal investigator, Department of Anaesthesiology and Intensive Care, Horsens Regional Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03908060
- Sponsor's protocol ID
- 01052019
- Status last verified
- Oct 2022
- First submitted
- 5 Apr 2019
- Last updated
- 2 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Marymont JH, Shear T, Parikh KN, Patel SS, Gupta DK. Intraoperative Methadone for the Prevention of Postoperative Pain: A Randomized, Double-blinded Clinical Trial in Cardiac Surgical Patients. Anesthesiology. 2015 May;122(5):1112-22. doi: 10.1097/ALN.0000000000000633.
PubMed 25837528Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Shear TD, Deshur MA, Vender JS, Benson J, Newmark RL. Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Posterior Spinal Fusion Surgery: A Randomized, Double-blinded, Controlled Trial. Anesthesiology. 2017 May;126(5):822-833. doi: 10.1097/ALN.0000000000001609.
PubMed 28418966Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg. 2011 Jan;112(1):218-23. doi: 10.1213/ANE.0b013e3181d8a095. Epub 2010 Apr 24.
PubMed 20418538Richlin DM, Reuben SS. Postoperative pain control with methadone following lower abdominal surgery. J Clin Anesth. 1991 Mar-Apr;3(2):112-6. doi: 10.1016/0952-8180(91)90007-a.
PubMed 2039637Chui PT, Gin T. A double-blind randomised trial comparing postoperative analgesia after perioperative loading doses of methadone or morphine. Anaesth Intensive Care. 1992 Feb;20(1):46-51. doi: 10.1177/0310057X9202000109.
PubMed 1609941Friesgaard KD, Brix LD, Kristensen CB, Rian O, Nikolajsen L. Clinical effectiveness and safety of intraoperative methadone in patients undergoing laparoscopic hysterectomy: a randomised, blinded clinical trial. BJA Open. 2023 Aug 5;7:100219. doi: 10.1016/j.bjao.2023.100219. eCollection 2023 Sep.
PubMed 37638083
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Laparoscopic Hysterectomy: a Prospective, Double-blind, Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT03908060
- Acronym / sponsor ID
- 01052019
- Conditions
- Postoperative Pain
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 126 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Study start
- 6 May 2019 (actual)
- Primary completion
- 8 Jul 2022 (actual)
- Study completion
- 1 Dec 2022 (estimated)
- First posted
- 9 Apr 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.
The role of a single-dose of intraoperative methadone on postoperative pain and opioid consumption in patients undergoing hysterectomy remains scarcely explored. A prospective double-blind, randomised controlled trial investigating the effect of a single-dose of intraoperative methadone in patients scheduled for same day hysterectomy is therefore conducted.
Detailed description
Background with aim: Hysterectomy is the most common major gynaecological procedure in the world and hysterectomy on benign indications are increasingly being performed as same-day surgery. Therefore, perioperative anaesthesia has moved towards the use of very short-acting opioids with the incitement to speed up extubation and facilitate hospital discharge. However, the potential consequence is that more patients experience pain and discomfort.
Methadone has several desirable pharmacological features, and a single intraoperative dose of the long acting opioid could therefore theoretically expand the analgesic window and reduce postoperative opioid consumption compared to the more conventional use of short-acting opioids. The aim of this study is to investigate the effect of a single-dose of intravenous intraoperative methadone on postoperative opioid consumption, pain and side effects in patients scheduled for hysterectomy for benign indications. Our primary hypothesis is that intravenous perioperative methadone reduces opioid consumption (oral cumulative equivalent dose) by 30% during the first 24 postoperative hours compared to intravenous morphine.
Methods: 126 patients will be included in an investigator-initiated, prospective, randomised, double-blind, controlled trial with two arms: an intervention arm (methadone 0.2 mg/kg ideal body weight) and a control arm (morphine 0.2 mg/kg ideal body weight). The study will be GCP-monitored, and is approved by the Danish Health and Medicines Authority (2018-004351-20) and the Central Denmark Region Committees on Health Research Ethics (1-10-72-365-18).
Hypothesis: The results will probably be applicable to other types of surgery involving visceral pain, and thus the present study has the potential to improve the pain management for a large number of patients undergoing surgery.
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
- Randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| Intravenous single-dose methadone | Experimental | Drug: MethadoneA 10 ml syringe with 2 mg/ml of methadone will be prepared and and study drug will be administered as intravenous bolus dose (0.2 mg/kg) corresponding to 1 ml for every 10 kg of ideal body weight (height (cm) - 105). |
| Intravenous single-dose morphine | Active comparator | Drug: MorphineA 10 ml syringe with 2 mg/ml of morphine will be prepared and study drug will be administered as intravenous bolus dose (0.2 mg/kg) corresponding to 1 ml for every 10 kg of ideal body weight (height (cm) - 105). |
Who may qualify
- Ages
- 18 to 110 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients scheduled for elective laparoscopic hysterectomy for benign indications
Key exclusion criteria (17 listed)
- American Society of Anaesthesiologists (ASA) physical status IV or V
- prolonged QT-interval assessed by electrocardiogram (> 440 milliseconds)
- Existing treatment with medications prolonging the QT-interval
- Hysterectomy due to malignancy or acute bleeding disorders
- Allergy to study drugs
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 |
|---|---|---|
| MethadoneOne intravenous administration of methadone (0.2 mg/kg ideal body weight) | Drug | Intravenous single-dose methadone |
| MorphineOne intravenous administration of morphine (0.2 mg/kg ideal body weight) | Drug | Intravenous single-dose morphine |
Primary outcome
Opioid consumption at 24 hours after extubation (cumulative opioid consumption)
Time frame: 24 hours
cumulative opioid consumption in oral morphine equivalents
Opioid consumption at 6 hours after extubation (cumulative opioid consumption)
Time frame: 6 hours
cumulative opioid consumption in oral morphine equivalents
2 secondary outcomes
Pain intensity (NRS, 0-10) at rest and coughing
Time frame: 0-48 hours after extubation
Postoperative side effects/ adverse events (nausea and vomiting, sedation, hypoventilation, and hypoxemia)
Time frame: 0-72 hours after extubation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2022.
- Background: PubMed 25837528Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Marymont JH, Shear T, Parikh KN, Patel SS, Gupta DK. Intraoperative Methadone for the Prevention of Postoperative Pain: A Randomized, Double-blinded Clinical Trial in Cardiac Surgical Patients. Anesthesiology. 2015 May;122(5):1112-22. doi: 10.1097/ALN.0000000000000633.
- Background: PubMed 28418966Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Shear TD, Deshur MA, Vender JS, Benson J, Newmark RL. Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Posterior Spinal Fusion Surgery: A Randomized, Double-blinded, Controlled Trial. Anesthesiology. 2017 May;126(5):822-833. doi: 10.1097/ALN.0000000000001609.
- Background: PubMed 20418538Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg. 2011 Jan;112(1):218-23. doi: 10.1213/ANE.0b013e3181d8a095. Epub 2010 Apr 24.
- Background: PubMed 2039637Richlin DM, Reuben SS. Postoperative pain control with methadone following lower abdominal surgery. J Clin Anesth. 1991 Mar-Apr;3(2):112-6. doi: 10.1016/0952-8180(91)90007-a.
- Background: PubMed 1609941Chui PT, Gin T. A double-blind randomised trial comparing postoperative analgesia after perioperative loading doses of methadone or morphine. Anaesth Intensive Care. 1992 Feb;20(1):46-51. doi: 10.1177/0310057X9202000109.
- Derived from this study: PubMed 37638083Friesgaard KD, Brix LD, Kristensen CB, Rian O, Nikolajsen L. Clinical effectiveness and safety of intraoperative methadone in patients undergoing laparoscopic hysterectomy: a randomised, blinded clinical trial. BJA Open. 2023 Aug 5;7:100219. doi: 10.1016/j.bjao.2023.100219. eCollection 2023 Sep.
- Individual participant dataSharing planned: No
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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.
Kristian Friesgaard, MD, PhD principal investigator
Department of Anaesthesiology and Intensive Care, Horsens Regional Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Methadone and Morphine in people with Postoperative Pain, run by University of Aarhus at 1 site in Denmark.
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 1 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 2 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
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?
Opioid consumption at 24 hours after extubation (cumulative opioid consumption) (time frame: 24 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03908060, which also lists 6 linked publications.
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 2 Nov 2022.