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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01809106
Recruitment Status : Completed
First Posted : March 12, 2013
Results First Posted : November 20, 2015
Last Update Posted : December 24, 2015
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research

Brief 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.

Condition or disease Intervention/treatment Phase
Cancer Cancer Pain Drug: Morphine Drug: Fentanyl Drug: Buprenorphine Drug: Oxycodone Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 518 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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.
Study Start Date : April 2011
Actual Primary Completion Date : October 2014
Actual Study Completion Date : October 2014

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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).

Other Outcome Measures:
  1. 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%).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01809106

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Arcispedale S. Maria Nuova Azienda Ospedaliera
Reggio Emilia, RE, Italy, 42100
Ospedale S. Marta
Catania, Italy
Fondazione IRCCS - Istituto Nazionale dei Tumori
Milano, Italy
Istituto Scientifico San Raffaele
Milano, Italy
Azienda Ospedaliera Valtellina-Valchiavenna
Morbegno, Italy
Ospedale Civile di Piacenza
Piacenza, Italy, 29100
Sesto San Giovanni, Italy
Ospedale San Giovanni Battista di Torino
Torino, Italy, 10126
Ospedale Gradenigo
Torino, Italy
Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research
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Principal Investigator: Oscar Corli, MD Mario Negri Institute of Pharmacological Research - IRCCS
Additional Information:

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Mario Negri Institute for Pharmacological Research Identifier: NCT01809106    
Other Study ID Numbers: Studio CERP
First Posted: March 12, 2013    Key Record Dates
Results First Posted: November 20, 2015
Last Update Posted: December 24, 2015
Last Verified: October 2015
Keywords provided by Mario Negri Institute for Pharmacological Research:
cancer pain
major opioid
Additional relevant MeSH terms:
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Cancer Pain
Neurologic Manifestations
Analgesics, Opioid
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Adjuvants, Anesthesia
Anesthetics, Intravenous
Anesthetics, General
Narcotic Antagonists