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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Mario Negri Institute for Pharmacological Research
Sponsor:
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier:
NCT01809106
First received: March 8, 2013
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Cancer
Cancer Pain
Drug: Morphine
Drug: Fentanyl
Drug: Buprenorphine
Drug: Oxycodone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Mario Negri Institute for Pharmacological Research:

Primary Outcome Measures:
  • Proportion of Non-Responder (NR) patients [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Evaluation of the proportion of Non-Responder (NR) patients. 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.


Secondary Outcome Measures:
  • Proportion of full-responder [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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).


Other Outcome Measures:
  • The opioid escalation index [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    The proportion of subjects with an increase of opioid daily dose > 5% compared with the basal dosage (OEI%).


Estimated Enrollment: 600
Study Start Date: April 2011
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Morphine Drug: Morphine
60 mg /24 ore
Experimental: Oxycodone Drug: Oxycodone
40 mg /24 ore
Experimental: Buprenorphine Drug: Buprenorphine
35 microg/h
Experimental: Fentanyl Drug: Fentanyl
25 microg/h

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01809106

Contacts
Contact: Oscar Corli, MD oscar.corli@marionegri.it
Contact: Anna Roberto, Biol Sci D anna.roberto@marionegri.it

Locations
Italy
Arcispedale S. Maria Nuova Azienda Ospedaliera Recruiting
Reggio Emilia, RE, Italy, 42100
Principal Investigator: ERMANNO RONDINI, MD         
Ospedale S. Marta Recruiting
Catania, Italy
Principal Investigator: Sergio Chisari, MD         
Fondazione IRCCS - Istituto Nazionale dei Tumori Recruiting
Milano, Italy
Principal Investigator: Augusto Caraceni, MD         
Istituto Scientifico San Raffaele Recruiting
Milano, Italy
Principal Investigator: manuela Pacchioni, MD         
Azienda Ospedaliera Valtellina-Valchiavenna Recruiting
Morbegno, Italy
Principal Investigator: Donato Valenti, MD         
Ospedale Civile di Piacenza Recruiting
Piacenza, Italy, 29100
Principal Investigator: Luigi Cavanna, MD         
Multimedica Recruiting
Sesto San Giovanni, Italy
Principal Investigator: Ornella Gottardi, MD         
Ospedale San Giovanni Battista di Torino Recruiting
Torino, Italy, 10126
Principal Investigator: Libero Ciuffreda, MD         
Ospedale Gradenigo Recruiting
Torino, Italy
Principal Investigator: Alessandro Comandone, MD         
Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research
Investigators
Principal Investigator: Oscar Corli, MD Mario Negri Institute of Pharmacological Research - IRCCS
  More Information

Additional Information:
Publications:

Responsible Party: Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier: NCT01809106     History of Changes
Other Study ID Numbers: Studio CERP
Study First Received: March 8, 2013
Last Updated: March 25, 2014
Health Authority: Italy: The Italian Medicines Agency
Italy: Ethics Committee

Keywords provided by Mario Negri Institute for Pharmacological Research:
cancer pain
major opioid
analgesics

Additional relevant MeSH terms:
Analgesics
Analgesics, Opioid
Morphine
Fentanyl
Buprenorphine
Oxycodone
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Adjuvants, Anesthesia
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Narcotic Antagonists

ClinicalTrials.gov processed this record on September 16, 2014