Prospective Study About Clinical and Pharmacogenetic Safety of Opioid Use for Chronic Pain

NCT00916890 | Suspended Phase 4

• 1 other identifier: PT-SM-1-Op-Cancer
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 6

Brief Summary

Aim of this project is to customize the choice of the strong opioid in the treatment of cancer chronic pain through the identification of patient clinical history and pain characteristics, moreover in the analysis the investigators will also correlate the clinical efficacy and safety of opioid treatment with pharmacokinetic and pharmacogenetic patterns in order to identify variables able to predict the efficacy of the treatment or the patient susceptibility towards a specific treatment. Furthermore with this study the investigators want to identify the pharmacogenomic characterization responsible for pharmacokinetic variability in the conversion between morphine and other opioids, in order to validate the currently available conversion tables from a pharmacokinetic viewpoint, estimating the influence of the most common genetic polymorphisms, and if this characterization could be useful and cost-effective. This study will also focus on the specific clinical-pharmacological response in the elderly and between male and female and on the interactions between opioids and those anticonvulsant and antidepressant drugs routinely used in the pain therapy (study of pharmacovigilance).

Conditions

Chronic Pain

Keywords

Opioid pharmacogenetics; Opioid pharmacokinetic; Long-term opioid treatment; Cancer pain

Outcome Measures

Primary Outcomes (1)

• To identify the drug with the best clinical-pharmacological safety-efficacy profile among the four opioids: oral extended-release morphine, oral extended-release oxycodone, transdermal fentanyl and transdermal buprenorphine.

  We will define a treatment effective if it will produce a mean reduction of NRS values at least of 40% than basal values. Among all effective treatments, we will identify the best as the one that will have a reduction of NRS to a value of 4 or less in 90% of patients compared to the 70% of the others treatments. To evaluate pharmacological safety the plasma concentrations of the drugs and their metabolites will be measured. We will branch patients population in 3 groups to evaluate the correlation between clinical-pharmacological response and genetics (responder,partially and not responder)

  15 days after randomization (Reduction of at least 40% of median daily pain, on a NRS)

Secondary Outcomes (1)

• Pharmacokinetic of opioids and of their metabolites during long-term administration; correlation between specific genotypes and clinical response or the clinical/pharmacological susceptibility to side-effects on administration of a specific opioid.

  6 months (each patient will be followed for 6 month after enrollment with clinical/pharmacological evaluations once a month and if inefficacy, tolerance or side effects)

Study Arms (4)

Oral extended-release morphine

ACTIVE COMPARATOR

Drug: Morphine

Oral extended-release oxycodone

ACTIVE COMPARATOR

Drug: Oxycodone

Transdermal fentanyl

ACTIVE COMPARATOR

Drug: Fentanyl

Transdermal buprenorphine

ACTIVE COMPARATOR

Drug: Buprenorphine

Interventions

Morphine DRUG

After a titration phase with fast-release oral morphine, once the optimal dosage (no side effects and less than two rescue doses per day) is reached, an equipotent dose of oral sustained-release morphine will be randomly assigned to a patient.

Oral extended-release morphine

Oxycodone DRUG

After a titration phase with fast-release oral morphine, once the optimal dosage (no side effects and less than two rescue doses per day) is reached, an equipotent dose of oral extended-release oxycodone will be randomly assigned to a patient.

Oral extended-release oxycodone

Fentanyl DRUG

After a titration phase with fast-release oral morphine, once the optimal dosage (no side effects and less than two rescue doses per day) is reached, an equipotent dosage of transdermal fentanyl will be randomly assigned to a patient.

Transdermal fentanyl

Buprenorphine DRUG

After a titration phase with fast-release oral morphine, once the optimal dosage (no side effects and less than two rescue doses per day) is reached, an equipotent dosage of transdermal buprenorphine will be randomly assigned to a patient.

Transdermal buprenorphine

Eligibility Criteria

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

You may qualify if:

• Adult oncologic patients (\>= 18 years old)
• Chronic peripheral neuropathic and/or nociceptive pain
• Written informed consent

You may not qualify if:

• Pediatric patients
• Mental impaired patients
• Substance abuse disorder
• Opioid allergy
• History of opioids use or addiction
• Severe immunodeficiency, severe renal impairment, severe liver disease
• Cachectic state
• HIV positive patients

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead
• University of Pavia: collaborator

Study Sites (6)

Fondazione IRCCS Policlinico San Matteo

Pavia, Pavia, 27100, Italy

Location

Struttura Complessa di Medicina Interna - Ospedale Civile di Voghera - Azienda Ospedaliera provincia di Pavia

Voghera, Pavia, 27058, Italy

Location

Servizio di Anestesia e Rianimazione e Terapia Antalgica - Ospedale Sant'Orsola-Poliambulanza

Brescia, 25011, Italy

Location

Servizio di Anestesia e Rianimazione e Terapia Antalgica - Ospedale Mellino Mellini

Chiari, 25032, Italy

Location

Unità operativa di Anestesia e Rianimazione - Azienda Ospedaliera San Gerardo

Monza, 20052, Italy

Location

Unità operativa di Terapia Antalgica e Cure Palliative - Ospedale Infermi

Rimini, 47900, Italy

Location

Related Publications (1)

• De Gregori S, Minella CE, De Gregori M, Tinelli C, Ranzani GN, Govoni S, Allegri M, Regazzi M. Clinical pharmacokinetics of morphine and its metabolites during morphine dose titration for chronic cancer pain. Ther Drug Monit. 2014 Jun;36(3):335-44. doi: 10.1097/FTD.0000000000000009.

  PMID: 24595069 DERIVED

MeSH Terms

Conditions

Chronic Pain; Cancer Pain

Interventions

Morphine; Oxycodone; Fentanyl; Buprenorphine

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Codeine; Piperidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Massimo Allegri, MD

  IRCCS Foundation Policlinico "San Matteo", Pavia, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 9, 2009
• First Posted: June 10, 2009
• Study Start: February 1, 2009
• Primary Completion: February 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 9, 2014

Record last verified: 2014-01

Locations

IT (6)