AnalgesiaPhase 4NCT04391855
Wound Infiltration With Tramadol, Dexmedetomidine, or Magnesium Plus Ropivacaine for Pain Relief After Spine Surgery
A Phase 4 study testing Tramadol with ropivacaine, Dexmedetomidine with ropivacaine and Magnesium with ropivacaine in people with Analgesia and Pain, Postoperative, run by Aristotle University Of Thessaloniki at 1 site in Greece.
Trial summary
The rationale for multimodal analgesia is to achieve additive or synergistic analgesic properties while decreasing the incidence of side effects by reducing the dose of each agent. Nociceptive stimuli are known to activate the release of the excitatory amino acid glutamate in the dorsal horn of the spinal cord. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Analgesia, Pain, Postoperative, Spinal Stenosis
- What is being tested?
- Tramadol with ropivacaine, Dexmedetomidine with ropivacaine and Magnesium with ropivacaine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteGreece
- Study dates
- 10 May 2022to 10 Dec 2024
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients aged between 18 and 80 years
- ASA Physical status 1 to 3
- Elective or semi-elective one-level lumbar laminectomy or discectomy surgery
- Signed informed consent
Who cannot join
- Chronic use of opioids
- Drugs or alcohol abuse
- Neurological disorders
- Local anesthetics toxicity
- Myopathy
- Cardiac conductance disturbances
Show all 9Show fewer
- Hepatic failure
- Renal failure
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Wound Infiltration With Tramadol, Dexmedetomidine, or Magnesium Sulfate as Adjuncts to the Local Anesthetic on Pain Relief After Spine Surgery
The rationale for multimodal analgesia is to achieve additive or synergistic analgesic properties while decreasing the incidence of side effects by reducing the dose of each agent. Nociceptive stimuli are known to activate the release of the excitatory amino acid glutamate in the dorsal horn of the spinal cord. The resultant activation of NMDA receptors causes calcium entry into the cell and triggers central sensitization. This mechanism is involved in the perception of pain and mainly accounts for its persistence during the postoperative period.
Peri-incisional injection of local anesthetics is an effective method for pain relief after many surgical procedures, as it can reduce postoperative analgesic consumption. Ropivacaine is a propyl analog of bupivacaine with a longer duration of action with a much safer cardiotoxicity profile than bupivacaine. Thus, a combination of local anesthetic with other analgesic factors, such as opioids, dexmedetomidine, clonidine, ketamine, magnesium sulfate, dexamethasone is suggested for a better analgesic outcome.
Read more
Dexmedetomidine, a highly selective a2-adrenergic receptor agonist, has been the focus of interest for its broad spectrum (sedative, analgesic, and anesthetic sparing) properties, making it a useful and safe adjunct in many clinical applications. The intravenous, intramuscular, intrathecal, epidural, and perineural use of this agent enhances analgesic effects.
Tramadol hydrochloride is a synthetic analog of codeine that acts on both opioid (weak m receptor agonist) and nonopioid receptors (inhibits the reuptake of noradrenaline and serotonin as well as release stored serotonin from nerve endings) which play a crucial role in pain inhibition pathway. It also blocks nerve conduction which imparts its local anesthetics like action on peripheral nerves.
It was reported that NMDA antagonists could prolong the analgesic effect of bupivacaine to even a week, as well as inhibit hyperalgesia. Magnesium sulfate (MGS) is a non-competitive antagonist of N-methyl, D-aspartate (NMDA) receptors with an analgesic effect and is essential for the release of acetylcholine from the presynaptic terminals and, similar to calcium channel blockers (CCB), can prevent the entry of calcium into the cell.
Aim of the study is to evaluate and compare the postoperative analgesic efficacy of tramadol, dexmedetomidine, and magnesium when added to ropivacaine as an adjuvant for wound infiltration following spine surgery.
Read the detailed description
Each participant will receive standard monitoring (ECG, SpO2, capnography, SBP, oesophageal temperature) and intravenous access will be established. A standard anesthesia protocol will be applied involving propofol 2mg/kg (iv) and remifentanil in TCI (target-controlled infusion). Cis-atracurium 0.2 mg/kg (iv) will be given to facilitate endotracheal intubation. Anesthesia will be maintained with desflurane in a 50% air/O2 mixture A standard anesthesia protocol will be applied involving propofol 2mg/kg (iv) and remifentanil in TCI (target-controlled infusion). Cis-atracurium 0.2 mg/kg (iv) will be given to facilitate endotracheal intubation. Anesthesia will be maintained with air to oxygen mixture of 50%, and desflurane adjusted to achieve a target BIS between 40 and 50. Remifentanil target level will be titrated according to analgesic demands defined by a > 20% change of heart rate or blood pressure compared with baseline. The duration of both anesthesia and surgical procedure will be registered. Furthermore, the level of sedation upon anesthesia emergence will be recorded using the Ramsey sedation scale.
Postoperatively pain assessment will be performed by the Visual Analogue Scale (VAS) and Numerical Rating Scale (NRS) at anesthesia emergence and at 2, 4, 6, 12, 18, and 24 h after surgery conclusion. Time to first analgesic request and total analgesics consumption postoperatively (morphine equivalents) will be recorded.
Episodes of shivering, as well as episodes of nausea and vomiting (PONV) and other postoperative adverse events, will be recorded at emergence and 24 hours thereafter.
Finally, patients' global satisfaction will be assessed the second day and one month after surgery using the Quality of Recovery Scale(QoR-40). In the meantime, blood samples will be taken at the time before the surgical stimulus, 6 hours and 24 hours after wound infiltration to measure cortisol, TNF-a, and IL-6 plasma concentration.
- Conditions
- Analgesia, Pain, Postoperative, Spinal Stenosis, Spinal Disease
- Being tested
- Tramadol with ropivacaine, Dexmedetomidine with ropivacaine, Magnesium with ropivacaine, Ropivacaine plus normal saline
- Keywords
- analgesia, pain score, tramadol, dexmedetomidine, magnesium, opioid consumption, spine surgery
- Medical subject headings
- Agnosia, Pain, Postoperative, Spinal Stenosis, Spinal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tramadol with ropivacaineDrug
Also called TR
A solution of tramadol 2mg/kg with ropivacaine hydrochloride (10mg/ml) 100mg mixture making up a total volume of 15ml will be infiltrated in the surgical trauma area before closure.
Dexmedetomidine with ropivacaineDrug
Also called DR
A solution of dexmedetomidine 1μg/kg with ropivacaine hydrochloride (10mg/ml) 100mg mixture making up a total volume of 15ml will be infiltrated in the surgical trauma area before closure.
Magnesium with ropivacaineDrug
Also called MR
A solution of magnesium 10 mg/kg with ropivacaine hydrochloride (10mg/ml) 100mg mixture making up a total volume of 15ml will be infiltrated in the surgical trauma area before closure.
Ropivacaine plus normal salineDrug
Also called R
A solution of ropivacaine hydrochloride (10mg/ml) 100mg with 5ml of isotonic saline 0.9% mixture making up a total volume of 15ml will be infiltrated in the surgical trauma area before closure.
| Study group | Role | What they receive |
|---|---|---|
| Tramadol with ropivacaine | Experimental | Tramadol 2mg/kg with ropivacaine (10mg/ml) 100mg for wound infiltration Receives: Drug: Tramadol with ropivacaine |
| Dexmedetomidine with ropivacaine | Experimental | Dexmedetomidine 1μg/kg with ropivacaine (10mg/ml) 100mg for wound infiltration Receives: Drug: Dexmedetomidine with ropivacaine |
| Magnesium with ropivacaine | Experimental | Magnesium sulfate 10 mg/kg with ropivacaine (10mg/ml) 100mg for wound infiltration Receives: Drug: Magnesium with ropivacaine |
| Placebo with ropivacaine | Placebo comparator | Ropivacaine (10mg/ml) 100mg with 5ml isotonic saline for wound infiltration Receives: Drug: Ropivacaine plus normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Analgesics consumption postoperatively in morphine equivalents
The difference in analgesic consumption (assessed as mg of morphine equivalents) postoperatively after wound infiltration with tramadol plus ropivacaine, tramadol plus ropivacaine, magnesium sulfate plus ropivacaine or ropivacaine plus isotonic saline 0.9%
Measured: 24 hours after the emergence from anesthesia
Secondary outcomes (4)
Time to first analgesic request in minutes
The difference in the time frame (minutes) for analgesia request after emergence from anesthesia after wound infiltration with tramadol plus ropivacaine, tramadol plus ropivacaine, magnesium sulfate plus ropivacaine or ropivacaine plus isotonic saline 0.9%
Measured: 24 hours after the emergence from anesthesia
Pain intensity postoperatively
The difference in pain intensity postoperatively assessed by Visual Analogue Scale (graded from 0 defining absence of pain to 10 meaning extreme pain) or Numerical Pain Scale (graded from 0 defining no pain to 10 the worst pain ever experienced) after wound infiltration with tramadol plus ropivacaine, tramadol plus ropivacaine, magnesium sulfate plus ropivacaine or ropivacaine plus isotonic saline 0.9%
Measured: At 10 minutes after emergence from anesthesia, and 2, 4, 6, 12, 18 and 24 hours after the emergence from anesthesia
Plasma concentration of TNF-a and IL-6
Levels of TNF-a and IL-6 in pg/ml will be measured from blood samples at the times before surgical stimulus, at 6 hours and 24 hours after wound infiltration, as stress-response biomarkers.
Measured: Before wound infiltration, and at 6 and 24 hours thereafter
Plasma concentration of cortisol
Levels of cortisol (in mcg/dL) will be measured from blood samples at the times before surgical stimulus, at 6 hours and 24 hours after wound infiltration, as stress-response biomarkers.
Measured: Before wound infiltration, and at 6 and 24 hours thereafter
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2020
- Study start10 May 2022
- Primary completion8 Nov 2024
- Study completion10 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AnalgesiaStudies of the same condition, open and under way.
- More trials run by Aristotle University Of ThessalonikiThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aristotle University Of Thessaloniki
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Georgia Tsaousi, Aristotle University Of Thessaloniki
- Investigators
- Georgia Tsaousi, Principal investigator, Aristotle University Of Thessaloniki
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04391855
- Sponsor's protocol ID
- SpinInf
- Status last verified
- Sep 2026
- First submitted
- 13 May 2020
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Wound Infiltration With Tramadol, Dexmedetomidine, or Magnesium Sulfate as Adjuncts to the Local Anesthetic on Pain Relief After Spine Surgery
- ClinicalTrials.gov ID
- NCT04391855
- Acronym / sponsor ID
- SpinInf
- Conditions
- Analgesia, Pain, Postoperative, Spinal Stenosis, Spinal Disease
- Keywords
- analgesia, pain score, tramadol, dexmedetomidine, magnesium, opioid consumption, spine surgery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Aristotle University Of ThessalonikiUniversity, hospital or other
- Study start
- 10 May 2022 (actual)
- Primary completion
- 8 Nov 2024 (actual)
- Study completion
- 10 Dec 2024 (actual)
- First posted
- 18 May 2020 (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 rationale for multimodal analgesia is to achieve additive or synergistic analgesic properties while decreasing the incidence of side effects by reducing the dose of each agent. Nociceptive stimuli are known to activate the release of the excitatory amino acid glutamate in the dorsal horn of the spinal cord. The resultant activation of NMDA receptors causes calcium entry into the cell and triggers central sensitization. This mechanism is involved in the perception of pain and mainly accounts for its persistence during the postoperative period.
Peri-incisional injection of local anesthetics is an effective method for pain relief after many surgical procedures, as it can reduce postoperative analgesic consumption. Ropivacaine is a propyl analog of bupivacaine with a longer duration of action with a much safer cardiotoxicity profile than bupivacaine. Thus, a combination of local anesthetic with other analgesic factors, such as opioids, dexmedetomidine, clonidine, ketamine, magnesium sulfate, dexamethasone is suggested for a better analgesic outcome.
Dexmedetomidine, a highly selective a2-adrenergic receptor agonist, has been the focus of interest for its broad spectrum (sedative, analgesic, and anesthetic sparing) properties, making it a useful and safe adjunct in many clinical applications. The intravenous, intramuscular, intrathecal, epidural, and perineural use of this agent enhances analgesic effects.
Tramadol hydrochloride is a synthetic analog of codeine that acts on both opioid (weak m receptor agonist) and nonopioid receptors (inhibits the reuptake of noradrenaline and serotonin as well as release stored serotonin from nerve endings) which play a crucial role in pain inhibition pathway. It also blocks nerve conduction which imparts its local anesthetics like action on peripheral nerves.
It was reported that NMDA antagonists could prolong the analgesic effect of bupivacaine to even a week, as well as inhibit hyperalgesia. Magnesium sulfate (MGS) is a non-competitive antagonist of N-methyl, D-aspartate (NMDA) receptors with an analgesic effect and is essential for the release of acetylcholine from the presynaptic terminals and, similar to calcium channel blockers (CCB), can prevent the entry of calcium into the cell.
Aim of the study is to evaluate and compare the postoperative analgesic efficacy of tramadol, dexmedetomidine, and magnesium when added to ropivacaine as an adjuvant for wound infiltration following spine surgery.
Detailed description
Each participant will receive standard monitoring (ECG, SpO2, capnography, SBP, oesophageal temperature) and intravenous access will be established. A standard anesthesia protocol will be applied involving propofol 2mg/kg (iv) and remifentanil in TCI (target-controlled infusion). Cis-atracurium 0.2 mg/kg (iv) will be given to facilitate endotracheal intubation. Anesthesia will be maintained with desflurane in a 50% air/O2 mixture A standard anesthesia protocol will be applied involving propofol 2mg/kg (iv) and remifentanil in TCI (target-controlled infusion). Cis-atracurium 0.2 mg/kg (iv) will be given to facilitate endotracheal intubation. Anesthesia will be maintained with air to oxygen mixture of 50%, and desflurane adjusted to achieve a target BIS between 40 and 50. Remifentanil target level will be titrated according to analgesic demands defined by a > 20% change of heart rate or blood pressure compared with baseline. The duration of both anesthesia and surgical procedure will be registered. Furthermore, the level of sedation upon anesthesia emergence will be recorded using the Ramsey sedation scale.
Postoperatively pain assessment will be performed by the Visual Analogue Scale (VAS) and Numerical Rating Scale (NRS) at anesthesia emergence and at 2, 4, 6, 12, 18, and 24 h after surgery conclusion. Time to first analgesic request and total analgesics consumption postoperatively (morphine equivalents) will be recorded.
Episodes of shivering, as well as episodes of nausea and vomiting (PONV) and other postoperative adverse events, will be recorded at emergence and 24 hours thereafter.
Finally, patients' global satisfaction will be assessed the second day and one month after surgery using the Quality of Recovery Scale(QoR-40). In the meantime, blood samples will be taken at the time before the surgical stimulus, 6 hours and 24 hours after wound infiltration to measure cortisol, TNF-a, and IL-6 plasma concentration.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Tramadol with ropivacaine | Experimental | Drug: Tramadol with ropivacaineTramadol 2mg/kg with ropivacaine (10mg/ml) 100mg for wound infiltration |
| Dexmedetomidine with ropivacaine | Experimental | Drug: Dexmedetomidine with ropivacaineDexmedetomidine 1μg/kg with ropivacaine (10mg/ml) 100mg for wound infiltration |
| Magnesium with ropivacaine | Experimental | Drug: Magnesium with ropivacaineMagnesium sulfate 10 mg/kg with ropivacaine (10mg/ml) 100mg for wound infiltration |
| Placebo with ropivacaine | Placebo comparator | Drug: Ropivacaine plus normal salineRopivacaine (10mg/ml) 100mg with 5ml isotonic saline for wound infiltration |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult patients aged between 18 and 80 years
- ASA Physical status 1 to 3
- Elective or semi-elective one-level lumbar laminectomy or discectomy surgery
- Signed informed consent
Key exclusion criteria (9 listed)
- Chronic use of opioids
- Drugs or alcohol abuse
- Neurological disorders
- Local anesthetics toxicity
- Myopathy
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 |
|---|---|---|
| Tramadol with ropivacaineAlso: TRA solution of tramadol 2mg/kg with ropivacaine hydrochloride (10mg/ml) 100mg mixture making up a total volume of 15ml will be infiltrated in the surgical trauma area before closure. | Drug | Tramadol with ropivacaine |
| Dexmedetomidine with ropivacaineAlso: DRA solution of dexmedetomidine 1μg/kg with ropivacaine hydrochloride (10mg/ml) 100mg mixture making up a total volume of 15ml will be infiltrated in the surgical trauma area before closure. | Drug | Dexmedetomidine with ropivacaine |
| Magnesium with ropivacaineAlso: MRA solution of magnesium 10 mg/kg with ropivacaine hydrochloride (10mg/ml) 100mg mixture making up a total volume of 15ml will be infiltrated in the surgical trauma area before closure. | Drug | Magnesium with ropivacaine |
| Ropivacaine plus normal salineAlso: RA solution of ropivacaine hydrochloride (10mg/ml) 100mg with 5ml of isotonic saline 0.9% mixture making up a total volume of 15ml will be infiltrated in the surgical trauma area before closure. | Drug | Placebo with ropivacaine |
Primary outcome
Analgesics consumption postoperatively in morphine equivalents
Time frame: 24 hours after the emergence from anesthesia
The difference in analgesic consumption (assessed as mg of morphine equivalents) postoperatively after wound infiltration with tramadol plus ropivacaine, tramadol plus ropivacaine, magnesium sulfate plus ropivacaine or ropivacaine plus isotonic saline 0.9%
4 secondary outcomes
Time to first analgesic request in minutes
Time frame: 24 hours after the emergence from anesthesia
Pain intensity postoperatively
Time frame: At 10 minutes after emergence from anesthesia, and 2, 4, 6, 12, 18 and 24 hours after the emergence from anesthesia
Plasma concentration of TNF-a and IL-6
Time frame: Before wound infiltration, and at 6 and 24 hours thereafter
Plasma concentration of cortisol
Time frame: Before wound infiltration, and at 6 and 24 hours thereafter
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2026.
- 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.
Georgia Tsaousi principal investigator
Aristotle University Of Thessaloniki
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tramadol with ropivacaine, Dexmedetomidine with ropivacaine and Magnesium with ropivacaine in people with Analgesia and Pain, Postoperative, run by Aristotle University Of Thessaloniki at 1 site in Greece.
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 4 inclusion and 9 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 30 Sep 2026. 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 Greece. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Analgesics consumption postoperatively in morphine equivalents (time frame: 24 hours after the emergence from anesthesia). 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 30 Sep 2026.