Post Operative PainNCT01594047
Perioperative Opioid-induced Hyperalgesia and Its Prevention With Ketamine and Methadone
A study testing ketamine infusion and Methadone PCA in people with Post Operative Pain and Hyperalgesia, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
Trial summary
Background: In perioperative period inhibition of N-Methyl-D-Aspartate receptor prevents opioid-induced hyperalgesia and reduce postoperative opioid requirement after abdominal surgery. Methadone is both a µ-opioid receptor agonist like Morphine and a N-Methyl-D-Aspartate antagonist. Study Aim. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Post Operative Pain, Hyperalgesia
- What is being tested?
- ketamine infusion and Methadone PCA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 113 participants
- Where
- 1 siteItaly
- Study dates
- 1 Dec 2009to 1 Aug 2014
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patients undergoing open colo-rectal surgery
Who cannot join
- ASA status more than II, history of chronic pain, ischemic heart disease or chronic pulmonary disease, allergy to any drugs used in the protocol. Body Max Index more than 35.
Trial locations and contacts
1 site in 1 country.
About this study
Background: In perioperative period inhibition of N-Methyl-D-Aspartate receptor prevents opioid-induced hyperalgesia and reduce postoperative opioid requirement after abdominal surgery. Methadone is both a µ-opioid receptor agonist like Morphine and a N-Methyl-D-Aspartate antagonist. Study Aim. To evaluate the efficacy of intraoperative Ketamine and postoperative Methadone analgesia in preventing opioid-induced hyperalgesia after abdominal surgery.
Read the detailed description
not desired
- Conditions
- Post Operative Pain, Hyperalgesia
- Being tested
- ketamine infusion, Methadone PCA
- Keywords
- hyperalgesia, Patient controlled analgesia, morphine, methadone, ketamine
- Medical subject headings
- Pain, Postoperative, Hyperalgesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ketamine infusionDrug
Also called hyperalgesia-blocker
Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery
Methadone PCADrug
Also called hyperalgesia-blocker
Methadone administered by a PCA system (dose 2 mg, lock-out 12min.)
| Study group | Role | What they receive |
|---|---|---|
| zero/morphine | No intervention | Patient received a standard balance anaesthesia and morphine for post operative pain. |
| ketamine/morphine | Experimental | Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery. Receives: Drug: ketamine infusion |
| zero/metadone | Experimental | Methadone PCA Receives: Drug: Methadone PCA |
| ketamine/methadone | Experimental | Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery.
Methadone administered by a PCA system (dose 2 mg, lock-out 12min.). Receives: Drug: ketamine infusion; Drug: Methadone PCA |
What is being measured
The primary outcome is the main question the study is designed to answer.
the Extent of Hyperalgesia Area Proximal to Surgical Wound
Hyperalgesia is determined by stimulating with a won Fray hair N°16 along three lines at a right angle to the top, middle, and bottom sides of the surgical incision. Each line starts from the edge of the abdomen to the surgical incision.
Stimulation continue from the edge toward the surgical incision until the patients reported a worsening in sensation The distance from the incision to where sensation change was measured. The mean of the three assessments was used as a measure of the extent of the hyperalgesia area.
Measured: 24 and 48 hours after surgery
Secondary outcomes (2)
Pain Intensity Measured by a Numeric Rating Scale (NRS)
A Numerical Rating Scale (NRS) from 0 to 10 is used as a measure of pain intensity. Zero indicates the absence of any pain and 10 the worse pain never felt.
Measured: 24 and 48 hours after surgery
Opioid Consumption
Cumulative opioid consumption at 48 hours from surgery ( end of the study)
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2012 (estimated)
- Study start1 Dec 2009
- Primary completion1 Jun 2012
- Study completion1 Aug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Post Operative PainStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoThe 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
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Emiliano Tognoli, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
- Investigators
- Emiliano Tognoli, Principal investigator, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01594047
- Sponsor's protocol ID
- metadone
- Status last verified
- Sep 2025
- First submitted
- 5 May 2012
- Last updated
- 1 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Tognoli E, Proto PL, Motta G, Galeone C, Mariani L, Valenza F. Methadone for postoperative analgesia: contribution of N-methyl-D-aspartate receptor antagonism: A randomised controlled trial. Eur J Anaesthesiol. 2020 Oct;37(10):934-943. doi: 10.1097/EJA.0000000000001217.
PubMed 32516227
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Perioperative Opioid-induced Hyperalgesia and Its Prevention With Ketamine and Methadone
- ClinicalTrials.gov ID
- NCT01594047
- Acronym / sponsor ID
- metadone
- Conditions
- Post Operative Pain, Hyperalgesia
- Keywords
- hyperalgesia, Patient controlled analgesia, morphine, methadone, ketamine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 113 participants (actual)
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoUniversity, hospital or other
- Study start
- 1 Dec 2009 (actual)
- Primary completion
- 1 Jun 2012 (actual)
- Study completion
- 1 Aug 2014 (actual)
- First posted
- 8 May 2012 (estimated)
- Results
- Posted 2 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background: In perioperative period inhibition of N-Methyl-D-Aspartate receptor prevents opioid-induced hyperalgesia and reduce postoperative opioid requirement after abdominal surgery. Methadone is both a µ-opioid receptor agonist like Morphine and a N-Methyl-D-Aspartate antagonist. Study Aim. To evaluate the efficacy of intraoperative Ketamine and postoperative Methadone analgesia in preventing opioid-induced hyperalgesia after abdominal surgery.
Detailed description
not desired
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| zero/morphine | No intervention | –Patient received a standard balance anaesthesia and morphine for post operative pain. |
| ketamine/morphine | Experimental | Drug: ketamine infusionKetamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery. |
| zero/metadone | Experimental | Drug: Methadone PCAMethadone PCA |
| ketamine/methadone | Experimental | Drug: ketamine infusion, Drug: Methadone PCAKetamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery. Methadone administered by a PCA system (dose 2 mg, lock-out 12min.). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- patients undergoing open colo-rectal surgery
Key exclusion criteria (1 listed)
- ASA status more than II, history of chronic pain, ischemic heart disease or chronic pulmonary disease, allergy to any drugs used in the protocol. Body Max Index more than 35.
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 |
|---|---|---|
| ketamine infusionAlso: hyperalgesia-blockerKetamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery | Drug | ketamine/methadone, ketamine/morphine |
| Methadone PCAAlso: hyperalgesia-blockerMethadone administered by a PCA system (dose 2 mg, lock-out 12min.) | Drug | ketamine/methadone, zero/metadone |
Primary outcome
the Extent of Hyperalgesia Area Proximal to Surgical Wound
Time frame: 24 and 48 hours after surgery
Hyperalgesia is determined by stimulating with a won Fray hair N°16 along three lines at a right angle to the top, middle, and bottom sides of the surgical incision. Each line starts from the edge of the abdomen to the surgical incision. Stimulation continue from the edge toward the surgical incision until the patients reported a worsening in sensation The distance from the incision to where sensation change was measured. The mean of the three assessments was used as a measure of the extent of the hyperalgesia area.
2 secondary outcomes
Pain Intensity Measured by a Numeric Rating Scale (NRS)
Time frame: 24 and 48 hours after surgery
Opioid Consumption
Time frame: 48 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32516227Tognoli E, Proto PL, Motta G, Galeone C, Mariani L, Valenza F. Methadone for postoperative analgesia: contribution of N-methyl-D-aspartate receptor antagonism: A randomised controlled trial. Eur J Anaesthesiol. 2020 Oct;37(10):934-943. doi: 10.1097/EJA.0000000000001217.
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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.
Emiliano Tognoli principal investigator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ketamine infusion and Methadone PCA in people with Post Operative Pain and Hyperalgesia, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
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 1 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: finished, as of the sponsor's last update on 1 Oct 2025. 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 Italy. 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?
Yes. Results are posted in the registry (first posted 2 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
the Extent of Hyperalgesia Area Proximal to Surgical Wound (time frame: 24 and 48 hours after surgery). 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 NCT01594047, which also lists 1 linked publication.
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 1 Oct 2025.