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. (CERP)

November 20, 2015 updated by: Mario Negri Institute for Pharmacological Research
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

518

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Catania, Italy
        • Ospedale S. Marta
      • Milano, Italy
        • Fondazione IRCCS - Istituto Nazionale dei Tumori
      • Milano, Italy
        • Istituto Scientifico San Raffaele
      • Morbegno, Italy
        • Azienda Ospedaliera Valtellina-Valchiavenna
      • Piacenza, Italy, 29100
        • Ospedale Civile Di Piacenza
      • Sesto San Giovanni, Italy
        • Multimedica
      • Torino, Italy, 10126
        • Ospedale San Giovanni Battista di Torino
      • Torino, Italy
        • Ospedale Gradenigo
    • RE
      • Reggio Emilia, RE, Italy, 42100
        • Arcispedale S. Maria Nuova Azienda Ospedaliera

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fentanyl
Drug: Fentanyl
25 microg/h
Experimental: Buprenorphine
Drug: Buprenorphine
35 microg/h
Active Comparator: Morphine
Drug: Morphine
60 mg /24 ore
Experimental: Oxycodone
Drug: Oxycodone
40 mg /24 ore

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Non-Responder (NR) Participants
Time Frame: 28 days
Evaluation of the proportion of Non-Responder (NR) participants. NR correspond to the subjects who do not report any analgesic effects, with a P.I.D. (pain intensity difference) from visit 6 and visit 1 =/< 0%, (using a 0-10 NRS ). It includes the situations of average pain intensity "stable" or "worsened" at day 28 compared with baseline values.
28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Full-responder
Time Frame: 28 days
Evaluation of the proportion of subjects who report full analgesia (full responders: FR). FR is operationally defined as a patient with a P.I.D. =/> 30% from visit 6 and visit 1 (NRS 0 to 10).
28 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Opioid Escalation Index
Time Frame: 28 days
The proportion of subjects with an increase of opioid daily dose > 5% compared with the basal dosage (OEI%).
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mario Negri Institute for Pharmacological Research

Investigators

  • Principal Investigator: Oscar Corli, MD, Mario Negri Institute of Pharmacological Research - IRCCS

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2011

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

October 1, 2014

Study Registration Dates

First Submitted

March 8, 2013

First Submitted That Met QC Criteria

March 8, 2013

First Posted (Estimate)

March 12, 2013

Study Record Updates

Last Update Posted (Estimate)

December 24, 2015

Last Update Submitted That Met QC Criteria

November 20, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Studio CERP

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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