Prospective Pharmacogenetic Cohort Study of CYP2D6 Metabolizer Phenotype, Analgesic Failure, and Adverse Effects in Postoperative Patients Receiving Tramadol by Elastomeric Infusion Pump

NCT07810816 | Recruiting

• 1 other identifier: 025
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective pharmacogenetic cohort will enroll postoperative patients receiving a standardized tramadol-containing elastomeric analgesia pump. CYP2D6 genotype will be measured but will not determine treatment during the 72-hour study window. Participants with non-normal metabolizer phenotypes will be compared with normal metabolizers for analgesic treatment failure and adverse effects. Pain, rescue medication, pump discontinuation, sedation, respiratory status, nausea/vomiting, and other adverse events will be assessed at prespecified times.

Conditions

Acute Postoperative Pain; Tramadol Adverse Effect; Pharmacogenetic Variation

Keywords

CYP2D6; Tramadol; Pharmacogenetics; Analgesic Failure; Adverse Drug Reaction; Postoperative Pain

Outcome Measures

Primary Outcomes (1)

• Incidence of Analgesic Treatment Failure

  Proportion of participants with at least one prespecified failure criterion: pain score 4 or higher at two consecutive scheduled assessments despite protocol-allowed adjustment, rescue opioid above the locked threshold, premature pump discontinuation for inadequate analgesia, or replacement by another analgesic technique.

  1 week

Secondary Outcomes (2)

• Incidence of Tramadol-Related Adverse Effects

  1 week

• Phenotype-Specific Composite Outcome

  1 week

Study Arms (2)

Non-Normal CYP2D6 Phenotype

Participants classified by the validated assay as poor or ultrarapid metabolizers. Phenotype-specific subgroups will be analyzed separately.

Drug: Standardized Tramadol Elastomeric Analgesia Pump; Genetic: CYP2D6 Genotyping and Metabolizer Phenotype Assignment

Normal CYP2D6 Metabolizer

Participants classified as normal metabolizers by the prespecified genotype-to-phenotype translation algorithm.

Drug: Standardized Tramadol Elastomeric Analgesia Pump; Genetic: CYP2D6 Genotyping and Metabolizer Phenotype Assignment

Interventions

CYP2D6 Genotyping and Metabolizer Phenotype Assignment GENETIC

A validated clinical assay will detect prespecified CYP2D6 alleles and copy-number variation. Genotypes will be translated to activity score and metabolizer phenotype using a locked laboratory algorithm. Results will remain unavailable to the care team during the 72-hour observational window unless the ethics-approved safety plan requires disclosure. Linked arm/group(s): Non-Normal CYP2D6 Phenotype, Normal CYP2D6 Metabolizer.

Non-Normal CYP2D6 Phenotype; Normal CYP2D6 Metabolizer

Standardized Tramadol Elastomeric Analgesia Pump DRUG

All participants receive the same institutionally approved tramadol-based pump formulation, basal rate, duration, and allowed co-analgesics as routine care. Exact concentration, total dose, infusion rate, rescue regimen, and stopping criteria must be inserted in the final protocol. Linked arm/group(s): Non-Normal CYP2D6 Phenotype, Normal CYP2D6 Metabolizer.

Non-Normal CYP2D6 Phenotype; Normal CYP2D6 Metabolizer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults undergoing elective surgery who receive a standardized tramadol-containing elastomeric analgesia pump and consent to CYP2D6 genotyping.

You may qualify if:

• Elective surgery followed by the institution's standardized tramadol-containing elastomeric analgesia pump.
• Ability to report pain on a 0-to-10 numeric rating scale.
• Provision of a blood or buccal sample for CYP2D6 genotyping before or immediately after surgery.
• Written informed consent for genetic testing, storage of genotype data, and clinical follow-up.

You may not qualify if:

• Known tramadol allergy or contraindication.
• Chronic opioid therapy, opioid use disorder, or opioid tolerance requiring an individualized regimen.
• Severe renal or hepatic dysfunction outside the standardized pump eligibility criteria.
• Concomitant medication or condition that requires deviation from the standard pump before the first outcome assessment.
• Pregnancy or breastfeeding.
• Inability to provide reliable pain scores or complete 72-hour monitoring.

Sponsors & Collaborators

• Research Inc: lead

Study Sites (1)

Clinica Bioforma

Medellín, Antioquia, Colombia

RECRUITING

Related Publications (6)

• Ruano G, Kost JA. Fundamental Considerations for Genetically-Guided Pain Management with Opioids Based on CYP2D6 and OPRM1 Polymorphisms. Pain Physician. 2018 Nov;21(6):E611-E621.

  PMID: 30508992 BACKGROUND

• Zahari Z, Ismail R. Influence of Cytochrome P450, Family 2, Subfamily D, Polypeptide 6 (CYP2D6) polymorphisms on pain sensitivity and clinical response to weak opioid analgesics. Drug Metab Pharmacokinet. 2014;29(1):29-43. doi: 10.2133/dmpk.dmpk-13-rv-032. Epub 2013 Jun 11.

  PMID: 23759977 BACKGROUND

• Gan SH, Ismail R, Wan Adnan WA, Zulmi W. Impact of CYP2D6 genetic polymorphism on tramadol pharmacokinetics and pharmacodynamics. Mol Diagn Ther. 2007;11(3):171-81. doi: 10.1007/BF03256239.

  PMID: 17570739 BACKGROUND

• Cavallari LH, Myers RA, Chakraborty H, Skaar TC, Gray CF, Baye JF, Volpi S, Rider R, Cicali EJ, Elwood EN, Harris EC, Hines LJ, Nahid NA, Nguyen KA, Obeng AO, Parr JA, Ramos MA, Orlando LA, Prieto HA, Sadeghpour A, Singh R, Starostik P, Tillman EM, Wyatt C, Horowitz CR, Voora D, Blake KV, Parvataneni HK, Fillingim RB, Dexter PR, Peterson JF, Johnson JA; IGNITE Pragmatic Trials Network. CYP2D6-Guided Opioid Management and Postoperative Pain Control: A Randomized Clinical Trial. JAMA Netw Open. 2026 Feb 2;9(2):e2558299. doi: 10.1001/jamanetworkopen.2025.58299.

  PMID: 41719044 BACKGROUND

• Mahajna M, Abu Fanne R, Odeh M, Berkovitch M, Tannous E, Eyal S, Vinker S, Green I, Matok I. Influence of cytochrome P450 2D6*10/*10 genotype on the risk for tramadol associated adverse effects: a retrospective cohort study. Front Pharmacol. 2024 Feb 19;15:1358549. doi: 10.3389/fphar.2024.1358549. eCollection 2024.

  PMID: 38440181 BACKGROUND

• Percevault S, De La Gastine B, Varin L, Richard N, Fobe F, Plaud B, Daccache G, Compere V, Parienti JJ, Coquerel A, Loilier M, Bleyzac N, Bourguignon L, Lelong-Boulouard V, Goutelle S. Influence of CYP2D6 phenotype on the pharmacokinetics and pharmacodynamics of tramadol in patients treated for post-operative pain management. Anaesth Crit Care Pain Med. 2026 May;45(3):101781. doi: 10.1016/j.accpm.2026.101781. Epub 2026 Mar 4.

  PMID: 41791456 BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative; Drug-Related Side Effects and Adverse Reactions

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Chemically-Induced Disorders

Study Officials

• Edison Osorio, MD, plastic surgery

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Edison Osorio, MD, Plastic surgeon

CONTACT

+573226140611; info@edisonosorio.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Month
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2026
• First Posted: September 9, 2026
• Study Start: January 12, 2023
• Primary Completion: September 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 9, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CO (1)