RCT Comparing the Analgesic Efficacy of 4 Therapeutic Strategies Based on 4 Different Major Opioids (Fentanyl, Oxycodone, Buprenorphine vs Morphine) in Cancer Patients With Moderate/Severe Pain, at the Moment of Starting 3rd Step of WHO Analgesic Ladder.
Condition: Cancer; Cancer Pain
MeSH terms: Cancer Pain
Intervention: Morphine; Fentanyl; Buprenorphine; Oxycodone
Intervention description: 60 mg /24 ore; 25 microg/h; 35 microg/h; 40 mg /24 ore
Intervention MeSH terms: Fentanyl; Morphine; Oxycodone; Buprenorphine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 518.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: cancer pain; major opioid; analgesics

Summary:

      Pain, in neoplastic disease, is a symptom with severe negative impact on the quality of life
      of patients and a high incidence, with values around 70-90% in advanced and metastatic
      stages. Than 20 years the main reference for the pharmacological treatment of cancer pain are
      the guidelines produced by the World Health Organization (WHO). This document shows that the
      use of opioid drugs is the mainstay of treatment, with particular reference to opioids
      "major" (3 rd step of the analgesic ladder). The 4 opioids more most commonly prescribed in
      Italy (oral morphine and oxycodone, fentanyl and buprenorphine transdermal), based on the
      data currently available, have an analgesic effect would partly overlap but with different
      percentages of non-responders (NR), a different need to increase the dose over time to
      maintain adequate analgesia, a different action to the switch to another molecule for
      ineffectiveness analgesic. The observations described suggest that opioids, although they
      belong to the same family drug may not be fully comparable with regard to the clinical
      effects products. Important differences are known on the pharmacokinetic and pharmacodynamic
      and, more recently, also in terms of pharmacogenomics. This is a comparative study of
      analgesic strategies based on the use of the 4 mentioned opioids, going to look for possible
      differences in terms of analgesic efficacy, changes in dose over time, use of switch or
      permanent abandonment of treatment, parallel to the contour of the side effects. The
      associated sub-project will link the structure gene of patients and clinical results have
      emerged.
    

Eligibility criteria:

        Inclusion Criteria:

          -  patients with diagnostic (histological or cytological) evidence of locally advanced or
             metastatic solid tumour;

          -  with average pain intensity ≥ 4, measured with NRS and related to the last 24 hours,
             due to the cancer, requiring for the first time an analgesic treatment with 3rd
             step/WHO opioids

          -  with life expectancy > one month

          -  "strong" opioid naïve;

          -  eligible to take any of the medications under evaluation, by TDS or by mouth;

          -  with age ≥ 18 years;

        Exclusion Criteria:

          -  Patients recruited in other researches that conflict or may confound the conduction
             and results of the present study;

          -  Lack of informed consent;

          -  with presence of other diseases, including psychiatric/mental illness, severe senile
             or other form of dementia, that can interfere with participation and compliance with
             the study protocol or can contraindicate the use of the investigational drugs;

          -  with presence of co-morbidities, which could create potentially dangerous drug
             interactions with opioids (eg, use of macrolide antibiotics or antifungal,….);

          -  any kind of contraindications to the use of opioid drugs;

          -  Patients with a known story, past or current, of drugs abuse or addiction;

          -  Use of drugs which presents a combination of opioids and other molecule (as NSAIDs,
             paracetamol, naloxone, ..);

          -  Patients who cannot guarantee regular follow-up visits for logistic or geographic
             reasons;

          -  Need of starting 3rd step treatment in an "emergency clinical situation" that do not
             allow the correct procedures of randomization;

          -  diagnosis of primary brain tumor or leukaemia;

          -  diagnosis of chronic renal failure;

          -  patients with antalgic radiotherapy or radio-metabolic therapy in progress or
             completed less than 14 days before study;

          -  patients starting a first line chemotherapy simultaneously to the beginning of the
             study;

          -  other types of analgesic treatments, including local-regional anesthetic techniques or
             neurosurgical /ablative methods.