search
Back to results

Effects of Switching From Racemic Methadone to R-methadone on QTc Intervals (MePhaCard)

Primary Purpose

Adverse Drug Effect, Drug Effect, Heart Arrhythmia

Status
Unknown status
Phase
Phase 4
Locations
Norway
Study Type
Interventional
Intervention
Same individuals treated with racemic methadone and switched to levomethadone (R-methadone)
Sponsored by
Oslo University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adverse Drug Effect focused on measuring Racemic methadone, R-methadone, QTc interval, Methadone maintenance treatment patients

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Stabilized on daily methadone dose
  • Not using other drugs of abuse
  • QTc-time recorded automatically, patient inclusion if QTc interval was greater or equal to 450 ms
  • Older than 18 years
  • Can sign and understand a written Consent

Exclusion Criteria:

  • Can not cooperate regarding observed daily drug intake
  • Serious psychiatric disease
  • Untreated serious somatic disease
  • Pregnancy

Sites / Locations

  • Department of Pharmacology , Oslo University Hospital
  • Department of Pharmacology and Department of Substance Use Disorder, Oslo University Hospital
  • Department of Substance Use Disorder, Oslo University Hospital

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Cross over study before and after drug switch

Arm Description

Stabilized on racemic methadone dose, switched to R-methadone of half racemic methadone dose. Cross over study, own control

Outcomes

Primary Outcome Measures

Effects of switching from racemic methadone to R-methadone on serum methadone concentrations.
Ten patients stabilized on racemic methadone dose were switched to R-methadone and effects on serum methadone concentrations were studied. Methadone concentrations (nmol/L) were measured by validated high pressure liquid chromatography coupled to mass spectrometry detection (LC-MSMS).
Effects of switching from racemic methadone to R-methadone on QTc interval
In ten patients QTc intervals were recorded on racemic methadone treatment at Cmin and Cmax of methadone drug concentrations and likewise after the shift to R-methadone. QT intervals (ms) on ECG were recorded automatically and read manually by experienced cardiologists.
Effects of switching from racemic methadone to R-methadone on opioid withdrawal symptoms (OWS)
Ten patients: each patients had OWS recorded on racemic and R-methadone treatment using OWS.
Effects of switching from racemic methadone to R-methadone, stability of serum electrolytes (Ca, Mg, K) in patients
Ten patients: samples for serum electrolytes were collected before and after switch to R-methadone. Measured by routine analysis at Cobas 8000 (unit mmol/L)

Secondary Outcome Measures

Full Information

First Posted
January 6, 2020
Last Updated
October 21, 2021
Sponsor
Oslo University Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT04254731
Brief Title
Effects of Switching From Racemic Methadone to R-methadone on QTc Intervals
Acronym
MePhaCard
Official Title
The Study of Potential Normalization of Cardiac Rhythm Following Drug Exchange From Chimeric Methadone to Active Methadone
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Unknown status
Study Start Date
May 7, 2015 (Actual)
Primary Completion Date
June 27, 2018 (Actual)
Study Completion Date
April 30, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oslo University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Effects of switching from racemic methadone to R-methadone on serum methadone concentrations and QTc intervals
Detailed Description
Racemic methadone may prolong the QTc interval, which is associated with fatal arrhythmias. In vitro studies have shown that R-methadone has less inhibitory effect than S-methadone on the voltage-gated potassium channel current, and is thus thought to have less effect on the QTc interval. The investigators hypothesized that switching from racemic to R-methadone would reduce the methadone serum concentration and also its effect on the QTc interval.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adverse Drug Effect, Drug Effect, Heart Arrhythmia
Keywords
Racemic methadone, R-methadone, QTc interval, Methadone maintenance treatment patients

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
Patients included were stabilized on per os methadone maintenance treatment and had automatically ECG recorded QTc interval greater or equal to 450 ms. The patients were switched to pure R-methadone per os (half dose of the racemic methadone used). Doses, serum drug concentrations, QTc-time were recorded before and after drug switch. Serum-electrolytes (Mg, K, Ca) and opioid withdrawal symptom scale (OWS) were also measured and scored before and after drug switch.
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cross over study before and after drug switch
Arm Type
Other
Arm Description
Stabilized on racemic methadone dose, switched to R-methadone of half racemic methadone dose. Cross over study, own control
Intervention Type
Drug
Intervention Name(s)
Same individuals treated with racemic methadone and switched to levomethadone (R-methadone)
Other Intervention Name(s)
Drugs provided from the pharmaceutical company called DnePharma AS (Den norske Eterfabrikk ( DnE), address Karihaugen 22, Oslo, Norway, drug delivered to patient from home nurse or pharmacy
Primary Outcome Measure Information:
Title
Effects of switching from racemic methadone to R-methadone on serum methadone concentrations.
Description
Ten patients stabilized on racemic methadone dose were switched to R-methadone and effects on serum methadone concentrations were studied. Methadone concentrations (nmol/L) were measured by validated high pressure liquid chromatography coupled to mass spectrometry detection (LC-MSMS).
Time Frame
Time frame of each patient form inclusion to end study was 35-40 days.
Title
Effects of switching from racemic methadone to R-methadone on QTc interval
Description
In ten patients QTc intervals were recorded on racemic methadone treatment at Cmin and Cmax of methadone drug concentrations and likewise after the shift to R-methadone. QT intervals (ms) on ECG were recorded automatically and read manually by experienced cardiologists.
Time Frame
Time frame of each patient form inclusion to end study was 35-40 days.
Title
Effects of switching from racemic methadone to R-methadone on opioid withdrawal symptoms (OWS)
Description
Ten patients: each patients had OWS recorded on racemic and R-methadone treatment using OWS.
Time Frame
Time frame of each patient form inclusion to end study was 35-40 days.
Title
Effects of switching from racemic methadone to R-methadone, stability of serum electrolytes (Ca, Mg, K) in patients
Description
Ten patients: samples for serum electrolytes were collected before and after switch to R-methadone. Measured by routine analysis at Cobas 8000 (unit mmol/L)
Time Frame
Time frame of each patient form inclusion to end study was 35-40 days.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Stabilized on daily methadone dose Not using other drugs of abuse QTc-time recorded automatically, patient inclusion if QTc interval was greater or equal to 450 ms Older than 18 years Can sign and understand a written Consent Exclusion Criteria: Can not cooperate regarding observed daily drug intake Serious psychiatric disease Untreated serious somatic disease Pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mimi Stokke S Opdal, MD, PhD
Organizational Affiliation
Oslo University Hospital and University of Oslo
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Peter Krajci, MD, PhD
Organizational Affiliation
Oslo University Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Department of Pharmacology , Oslo University Hospital
City
Oslo
ZIP/Postal Code
0424
Country
Norway
Facility Name
Department of Pharmacology and Department of Substance Use Disorder, Oslo University Hospital
City
Oslo
ZIP/Postal Code
0424
Country
Norway
Facility Name
Department of Substance Use Disorder, Oslo University Hospital
City
Oslo
ZIP/Postal Code
0424
Country
Norway

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD can be shared when the manuscript has been accepted for publication.
IPD Sharing Time Frame
Protocol in Norwegian attached
IPD Sharing Access Criteria
IPD proving the results of the different outcome measures will be shared, see above
Links:
URL
https://link.springer.com/content/pdf/10.1007%2Fs00228-019-02685-2.pdf
Description
abstract from EACPT 2019, see abstract 1168

Learn more about this trial

Effects of Switching From Racemic Methadone to R-methadone on QTc Intervals

We'll reach out to this number within 24 hrs