Switching From Morphine to Methadone. A Clinical, Pharmacological and Pharmacogenetic Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Norwegian University of Science and Technology
ClinicalTrials.gov Identifier:
NCT00184496
First received: September 15, 2005
Last updated: February 27, 2014
Last verified: February 2014

September 15, 2005
February 27, 2014
August 2004
September 2009   (final data collection date for primary outcome measure)
The overall aim of the present study is to validate the switching procedure from morphine to methadone for patients with advanced cancer and a short life expectancy. More specifically, we will: [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • The overall aim of the present study is to validate the switching procedure from morphine to methadone for patients with advanced cancer and a short life expectancy. More specifically, we will:
  • • Compare different switching strategies, i.e. “stop and go” versus three days of switching with clinical and pharmacological outcomes.
  • • Evaluate a standard equianalgesic recommendation in a clinical and from a pharmacological perspective.
Complete list of historical versions of study NCT00184496 on ClinicalTrials.gov Archive Site
  • Collect blood samples for present and future genetic analyses in order to explore inter individual variations in methadone and morphine doses based upon possible polymorphisms. [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Compare the QT-intervals on electrocardiograms obtained before and after start with methadone. [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
  • Collect blood samples for present and future genetic analyses in order to explore inter individual variations in methadone and morphine doses based upon possible polymorphisms.
  • • Compare the QT-intervals on electrocardiograms obtained before and after start with methadone.
Not Provided
Not Provided
 
Switching From Morphine to Methadone. A Clinical, Pharmacological and Pharmacogenetic Study
Switching From Morphine to Methadone. A Clinical, Pharmacological and Pharmacogenetic Study

Cancer patients on morphine for chronic pain, with side effects or unsatisfactory pain relief, will be rotated to Methadone. We will try to find out what is the best methode to rotate, and the equivalent dosage.

This study is based on the clinical observation that patients who are not well controlled on morphine or oxycodone may benefit from switching to another opioid, in this case methadone. Although the mechanism for such switch is not completely understood, evidence indicates that opioids with different chemical structures have different characteristics, not least in relation to new knowledge about genetic variation in opioid receptors. Another challenge is that there is much uncertainty regarding equianalgesic dose ratios for morphine and methadone. It seems that the higher the morphine doses, the relatively lower methadone doses are needed to substitute morphine. Furthermore, there is uncertainty to which switching procedures one should use, the most common ones are "stop and go" and a three days switch. Finally, it is reported that methadone may increase the QT interval of the ECG, and thus increase the risk for the ventricular arrhythmia Torsade de pointe. The aim of this randomized, open label, multicenter study is primarily to compare the switching procedures, but it will also provide more knowledge about equianalgesic dose ratios, the effect of methadone on the QT interval, genetical factors that may characterize patients needing opioid switch as well as their response to it, and finally if pharmacokinetic factors plays a role.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Cancer
Drug: Methadone
To methods for switching morphine to methadon. Stop-and go versus overlap
  • Active Comparator: methadon
    Morphine methadone stop and go switch
    Intervention: Drug: Methadone
  • Active Comparator: Methadone
    Methadon morphine overlap switch
    Intervention: Drug: Methadone
Moksnes K, Dale O, Rosland JH, Paulsen O, Klepstad P, Kaasa S. How to switch from morphine or oxycodone to methadone in cancer patients? a randomised clinical phase II trial. Eur J Cancer. 2011 Nov;47(16):2463-70. doi: 10.1016/j.ejca.2011.06.047. Epub 2011 Jul 19.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
42
September 2009
September 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • • Malignant disease.

    • On morphine and in need of opioid rotation. (A patient in need of opioid rotation is defined as having insufficient pain control with or without unacceptable side effects from opioids).
    • Able to complete the planned assessment schedules.
    • Above 18 years of age.
    • If out-patient, the patient lives with someone who can observe him/her.
    • Given informed consent according to the ethical guidelines.

Exclusion Criteria:

  • Not able to read or write in Norwegian
  • The patient has participated in a clinical study 4 weeks prior to inclusion
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Norway
 
NCT00184496
OPI 03/008
No
Norwegian University of Science and Technology
Norwegian University of Science and Technology
Not Provided
Principal Investigator: Stein Kaasa, MD,PhD Prof. St Olavs University Hospital, Trondheim
Norwegian University of Science and Technology
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP