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

Phase 3

Completed

• Conditions: Cancer
• Interventions: Drug: Methadone

• Registration Number: NCT00184496
• Lead Sponsor: Norwegian University of Science and Technology

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2004-08
• Study First Submitted: 2005-09-15
• Study First Submitted QC: 2005-09-15
• Study First Posted: 2005-09-16
• Primary Completion: 2009-09
• Study Completion: 2009-09
• Status Verified: 2014-02
• Last Update Submitted: 2014-02-27
• Last Update Posted: 2014-02-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Methadone	Methadone	Methadon morphine overlap switch
methadon	Methadone	Morphine methadone stop and go switch

Primary Outcome Measures

Name	Time	Method
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:	2 weeks

Secondary Outcome Measures

Name	Time	Method
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.	2 weeks
Compare the QT-intervals on electrocardiograms obtained before and after start with methadone.	2 weeks

Trial Locations

Locations (1)

St Olavs Hospital; 🇳🇴 Trondheim, Norway