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NCT04004481: METRAS

Metabolites of Tramadol in the Postoperative Surgical Patients

Completed Results posted Last updated 9 July 2021
What this trial tests

trial testing Postoperative analgesia using tramadol in Abdominal Surgery in 50 participants. Completed in 13 March 2020.

Timeline
25 January 2019
Primary endpoint
28 February 2020
13 March 2020

Quick facts

Lead sponsorOsijek University Hospital
StatusCompleted
Study typeOBSERVATIONAL
Enrollment50
Start date25 January 2019
Primary completion28 February 2020
Estimated completion13 March 2020
Sites1 location across Croatia

Drugs / interventions tested

Conditions studied

Sponsor

Osijek University Hospital

Who can join

Adults 18 to 90, any sex, with Abdominal Surgery or Respiratory Failure. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Serum Concentration of Tramadol and Tramadol Metabolites With Respect to Metabolic Phenotype Primary · 1, 2, and 4 hours after first dose and immediately before 2nd, 3rd, and 5th dose, up to 24 hours

The plasma concentrations of tramadol, O-desmethyltramadol (ODT) and N-desmethyltramadol (NDT) will be measured 1, 2 and 4 hours after the first dose of 100 mg tramadol i.v., and immediately before the 2nd, 3rd and 5th dose. There will therefore be 6 measurements of tramadol and its metabolites.

1st measurement
GroupValue95% CI
Tramadol Concentration372.7250.6 – 535.7
ODT Concentration in Poor Metabolizers (PM)7.054.52 – 7.05
ODT Concentration in Intermediate Metabolizers (IM)17.16.3 – 38.1
ODT Concentration in Extensive Metabolizers (EM)40.921.9 – 53.9
ODT Concentration in Ultrafast Metabolizers (UM)13.8
NDT Concentration in Poor Metabolizers (PM)11.77.6 – 11.7
NDT Concentration in Intermediate Metabolizers (IM)4.53.5 – 11.1
NDT Concentration in Extensive Metabolizers (EM)4.763.5 – 19.1
NDT Concentration in Ultrafast Metabolizers (UM)3.5
2nd measurement
GroupValue95% CI
Tramadol Concentration270.6201.6 – 447.9
ODT Concentration in Poor Metabolizers (PM)7.64.5 – 7.6
ODT Concentration in Intermediate Metabolizers (IM)15.77.3 – 39.6
ODT Concentration in Extensive Metabolizers (EM)46.723.6 – 64.3
ODT Concentration in Ultrafast Metabolizers (UM)19.4
NDT Concentration in Poor Metabolizers (PM)15.39.2 – 15.3
NDT Concentration in Intermediate Metabolizers (IM)6.13.9 – 12.2
NDT Concentration in Extensive Metabolizers (EM)5.23.5 – 22
NDT Concentration in Ultrafast Metabolizers (UM)3.5
3rd measurement
GroupValue95% CI
Tramadol Concentration232.1153.5 – 369.8
ODT Concentration in Poor Metabolizers (PM)104.6 – 10
ODT Concentration in Intermediate Metabolizers (IM)20.212.5 – 40.4
ODT Concentration in Extensive Metabolizers (EM)46.431 – 72.6
ODT Concentration in Ultrafast Metabolizers (UM)26
NDT Concentration in Poor Metabolizers (PM)28.912.3 – 28.9
NDT Concentration in Intermediate Metabolizers (IM)9.15.3 – 14.7
NDT Concentration in Extensive Metabolizers (EM)8.53.6 – 22.9
NDT Concentration in Ultrafast Metabolizers (UM)3.5
4th measurement
GroupValue95% CI
Tramadol Concentration181.2122.9 – 270.2
ODT Concentration in Poor Metabolizers (PM)12.45.2 – 12.4
ODT Concentration in Intermediate Metabolizers (IM)19.111.4 – 47.8
ODT Concentration in Extensive Metabolizers (EM)38.130.3 – 74.5
ODT Concentration in Ultrafast Metabolizers (UM)25.1
NDT Concentration in Poor Metabolizers (PM)31.215.7 – 31.2
NDT Concentration in Intermediate Metabolizers (IM)9.65.1 – 20.7
NDT Concentration in Extensive Metabolizers (EM)9.73.5 – 23.9
NDT Concentration in Ultrafast Metabolizers (UM)3.5
5th measurement
GroupValue95% CI
Tramadol Concentration300.1191.8 – 417.6
ODT Concentration in Poor Metabolizers (PM)19.110.7 – 19.1
ODT Concentration in Intermediate Metabolizers (IM)36.621.2 – 71.4
ODT Concentration in Extensive Metabolizers (EM)75.146.3 – 117.6
ODT Concentration in Ultrafast Metabolizers (UM)58.2
NDT Concentration in Poor Metabolizers (PM)71.443 – 71.4
NDT Concentration in Intermediate Metabolizers (IM)20.210.5 – 37.2
NDT Concentration in Extensive Metabolizers (EM)197.4 – 45.6
NDT Concentration in Ultrafast Metabolizers (UM)9.8
6th measurement
GroupValue95% CI
Tramadol Concentration408.5273.8 – 677.8
ODT Concentration in Poor Metabolizers (PM)29.723.9 – 29.7
ODT Concentration in Intermediate Metabolizers (IM)51.725.7 – 93.5
ODT Concentration in Extensive Metabolizers (EM)97.452.6 – 139
ODT Concentration in Ultrafast Metabolizers (UM)61.9
NDT Concentration in Poor Metabolizers (PM)180.5124.9 – 180.5
NDT Concentration in Intermediate Metabolizers (IM)34.918.5 – 69.9
NDT Concentration in Extensive Metabolizers (EM)34.418.6 – 72.5
NDT Concentration in Ultrafast Metabolizers (UM)18.1
Analgesic Effect of Tramadol Measured by Numeric Rating Scale (NRS) Secondary · Before each dose of tramadol and 30 minutes after tramadol dose, up to 24 hours

The analgesic effect of tramadol will be measured in awake patients with Numeric Rating Scale (NRS, 0 - without pain, 10 - the worst pain) 30 minutes before and 30 minutes after tramadol administration. The NRS value of 3 or less will be considered as adequate analgesia. In case of inadequate analgesia morphine will be used according to the local protocol.

1st pain assessment
GroupValue95% CI
Median NRS Score Before Tramadol Administration73 – 9
Median NRS Score After Tramadol Administration53.5 – 6
2nd pain assessment
GroupValue95% CI
Median NRS Score Before Tramadol Administration53 – 6.75
Median NRS Score After Tramadol Administration31 – 4.75
3rd pain assessment
GroupValue95% CI
Median NRS Score Before Tramadol Administration3.52.25 – 5
Median NRS Score After Tramadol Administration21 – 3
4th pain assessment
GroupValue95% CI
Median NRS Score Before Tramadol Administration42 – 5
Median NRS Score After Tramadol Administration21 – 4
5th pain assessment
GroupValue95% CI
Median NRS Score Before Tramadol Administration32 – 5
Median NRS Score After Tramadol Administration21 – 3
Analgesic Effect of Tramadol Measured by Critical Care Pain Observation Tool (CPOT) Secondary · Pain was assessed before and 30 minutes after each tramadol dose, up to 24 hours.

In unconsciousness patents, the analgesic effect of tramadol will be tested by Critical Care Pain Observation Tool (CPOT). Highest score on a scale is 8 (worst pain) and lowest is 0 (no pain). The CPOT value of less than 2 will be considered as adequate analgesia.

1st assessment point
GroupValue95% CI
Median CPOT Score Before Tramadol Administration00 – 0
Median CPOT Score After Tramadol Administration00 – 0
2nd assessment point
GroupValue95% CI
Median CPOT Score Before Tramadol Administration00 – 0
Median CPOT Score After Tramadol Administration00 – 0
3rd assessment point
GroupValue95% CI
Median CPOT Score Before Tramadol Administration00 – 0
Median CPOT Score After Tramadol Administration00 – 0
4th assessment point
GroupValue95% CI
Median CPOT Score Before Tramadol Administration00 – 0
Median CPOT Score After Tramadol Administration00 – 0
5th assessment point
GroupValue95% CI
Median CPOT Score Before Tramadol Administration00 – 0
Median CPOT Score After Tramadol Administration00 – 0
Number of Participants With Nausea and Vomiting After Tramadol Secondary · Nausea and vomiting was assessed during first 30 minutes after tramadol administration

Nausea and/or vomiting during treatment with tramadol in ICU will be recorded.

GroupValue95% CI
PONV in EM12
PONV in IM4
Number of Patients With Respiratory Depression After Tramadol Secondary · Respiratory depression was observed up to 30 minutes after tramadol administration

Respiratory depression after tramadol is considered to be any drop in saturation below 90% or drop in respiratory rate below 10/min.

GroupValue95% CI
Number of Patients With Postoperative Respiratory Depression0
Length of ICU Stay Secondary · Up to 6 months

Length of stay in ICU will be recorded and correlated with standard laboratory values and tramadol and metabolites concentration.

GroupValue95% CI
Low Plasma Cholinesterase Activity1.51 – 6
Normal Plasma Cholinesterase Activity11 – 1

Adverse events — posted to ClinicalTrials.gov

Time frame: 24 hours. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PONV in EM
Serious: 0/22 (0%)
Deaths: 0/22
PONV in IM
Serious: 0/22 (0%)
Deaths: 0/22
Other adverse events (1 terms — click to expand)

ReactionSystemPONV in EMPONV in IM
PONVGastrointestinal disorders

Data from ClinicalTrials.gov NCT04004481 adverse events section.

Sponsor's own description

Tramadol is opioid analgesic widely used to treat moderate to severe pain. It is metabolized by cytochrome CYP2D6 into two major metabolites: pharmacologically active metabolite O-desmethyltramadol (M1) and inactive N-desmethyltramadol (M2), respectively. Tramadol kinetics in a population of patients undergoing major abdominal surgical procedures, and in patients with a greater or lesser degree of organic failure, is still not well researched. The investigators will measure plasma concentrations of tramadol and its metabolites after usual tramadol doses in ICU patients after major abdominal surgery. Also analgesic affect and side effect of tramadol will be recorded.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Different Pharmacokinetics of Tramadol, <i>O</i>-Demethyltramadol and <i>N</i>-Demethyltramadol in Postoperative Surgical Patients From Those Observed in Medical Patients.
    Neskovic N, Mandic D, Marczi S, Skiljic S, et al · · 2021 · cited 5× · PMID 33935773 · DOI 10.3389/fphar.2021.656748

Verify or expand the search:

Other recruiting trials for Abdominal Surgery

Currently open trials in the same condition.

Other Osijek University Hospital trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing