Clinical trial NCT04254731: Effects of Switching From Racemic Methadone to R-methadone on QTc Intervals
Official title: The Study of Potential Normalization of Cardiac Rhythm Following Drug Exchange From Chimeric Methadone to Active Methadone
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Adverse Drug Effect
Drug Effect
Heart Arrhythmia
Keywords: Racemic methadone
R-methadone
QTc interval
Methadone maintenance treatment patients
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
First posted: 2020-02-05
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Effects of switching from racemic methadone to R-methadone on serum methadone concentrations.
timeFrame: Time frame of each patient form inclusion to end study was 35-40 days.
measure: Effects of switching from racemic methadone to R-methadone on QTc interval
timeFrame: Time frame of each patient form inclusion to end study was 35-40 days.
measure: Effects of switching from racemic methadone to R-methadone on opioid withdrawal symptoms (OWS)
timeFrame: Time frame of each patient form inclusion to end study was 35-40 days.
measure: Effects of switching from racemic methadone to R-methadone, stability of serum electrolytes (Ca, Mg, K) in patients
timeFrame: Time frame of each patient form inclusion to end study was 35-40 days.
Secondary outcomes:
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Department of Pharmacology , Oslo University Hospital
city: Oslo
country: Norway
facility: Department of Pharmacology and Department of Substance Use Disorder, Oslo University Hospital
city: Oslo
country: Norway
facility: Department of Substance Use Disorder, Oslo University Hospital
Study officials:
affiliation: Oslo University Hospital and University of Oslo
name: Mimi Stokke S Opdal, MD, PhD
role: STUDY_DIRECTOR
affiliation: Oslo University Hospital
name: Peter Krajci, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Havig SM, Berg-Pedersen RM, Krabseth HM, Muller LD, Haugaa K, Zare HK, Gjesdal K, Krajci P, Opdal MS. Effect on QTc interval by switching from methadone to equipotent R-methadone dose in methadone maintenance treatment patients. Basic Clin Pharmacol Toxicol. 2024 Apr;134(4):519-530. doi: 10.1111/bcpt.13982. Epub 2024 Feb 3.