Methadone-Induced QT Interval Prolongation in a Narcotic Treatment Center

NCT02898337 | Completed

• 1 other identifier: 1608001774
• Study Type: observational
• Target: 170
• Locations: 1 country
• Sites: 1

Brief Summary

Torsades de pointes (TdP) is a polymorphic ventricular tachycardia associated with prolongation of the heart rate-corrected QT (QTc) interval on the electrocardiogram (ECG). TdP can result in catastrophic outcomes, including sudden cardiac death. QTc interval prolongation is a well-known adverse event associated with methadone use. While some risk factors for methadone-associated QTc interval prolongation and TdP have been identified, the contribution of interacting drugs and concomitant administration of other QTc interval-prolonging agents to overall risk has not been determined. The effect of ECG screening and monitoring on clinical outcomes in patients taking methadone has not been evaluated, and clinical opinion regarding routine ECG and risk factor monitoring varies. Twelve lead ECGs are costly and time-intensive for clinic staff. ECG screening in selected patients based on presence of QTc interval risk factors, rather than broadly in all patients taking methadone, would facilitate more targeted, strategic QTc interval monitoring. The FDA-approved AliveCor® handheld smart phone/tablet device records a single lead ECG (iECG) within 30 seconds. Use of this device may facilitate simpler, more rapid and less costly ECG monitoring in patients receiving care in narcotic treatment centers. Our long-term goals are to determine mechanisms by which drugs cause arrhythmias, to identify patients at greatest risk of drug-induced arrhythmias, and to determine safe and effective methods for prevention and management of drug-induced arrhythmias. Specific Aim 1: Identify independent risk factors for methadone-induced QTc interval prolongation in patients undergoing care in a narcotic treatment center. Research Design: This will be a retrospective/prospective analysis of ECGs and health information from patients receiving methadone therapy in the Eskenazi Health Midtown Narcotic Treatment Center in Indianapolis, IN. Currently, at the Midtown Narcotic Treatment Center, baseline 12-lead ECGs are recorded for all patients prior to initiation of methadone therapy; follow-up ECGs are obtained approximately 2 weeks after methadone initiation only in patients with a baseline prolonged QTc interval. At the start of the study, methadone-treated patients who have not had follow-up ECGs on methadone therapy will be identified and contacted prospectively. Those consenting to participation will undergo a follow-up 12-lead ECG to determine QTc interval during methadone maintenance therapy. For all patients, retrospective analysis of the electronic medical record will be performed to document sex, pregnancy status, age, family history, current and past medical history, and concomitant use of prescribed, over the counter, and illicit drug use with the aim to identify all potential risks. QTc interval prolongation will be defined as QTc interval ≥ 500 ms or an increase in QTc interval of ≥ 60 ms compared with the baseline QTc interval. Electronic health information variables will be compared in patients who develop methadone-associated QTc interval prolongation versus those who do not using univariate analysis. Patients with prolonged QTc interval at baseline will be excluded from the study. Specific Aim 2: Validate the handheld AliveCor® smart phone/tablet iECG device as a simple, rapid method of monitoring QTc intervals in methadone-treated patients in a narcotic treatment center. Research Design: A separate cohort of patients will be utilized to validate the AliveCor® device for use in measuring QTc intervals in patients initiated and maintained on methadone in a narcotic treatment center. Twelve lead ECGs and simultaneous single lead ECGs using the AliveCor® device will be recorded for all newly enrolled patients at baseline and again after six weeks of methadone therapy. The QTc identified by the 12-lead ECG will be compared to the single lead ECG for all baseline and follow-up recordings to validate the use of the AliveCor® device for potential use in narcotic treatment centers to reduce cost and save time. Comparison of QTc intervals between the 12-lead and single lead measurements will be performed using the Bland-Altman method for analysis of measurement agreement. The mean and 95% confidence interval of the difference in QTc interval between the two methods will be calculated. This will be a pilot study to justify a larger extramural study to develop and validate a risk score for methadone-induced QTc interval prolongation and to use the handheld ECG device for QTc interval monitoring in patients identified as high-risk using this risk score. Our rationale is that identification of risk factors for methadone-induced QTc interval prolongation and quantification of degree of risk conferred by each risk factor will ultimately reduce the incidence and risk of QTc interval prolongation through targeted ECG monitoring of patients at highest risk and modulation of modifiable risk factors.

Conditions

QT Interval Prolongation

Outcome Measures

Primary Outcomes (1)

• QTc interval prolongation

  6 weeks

Study Arms (2)

Methadone-induced QTc interval prolongation

Device: AliveCor handheld mobile ECG

Methadone-treated patients, no QT interval prolongation

Device: AliveCor handheld mobile ECG

Interventions

AliveCor handheld mobile ECG DEVICE

Specific Aim 1: independent risk factors for methadone-associated QTc interval prolongation will be determined through retrospective analysis of electronic medical records of methadone-treated patients in a narcotic treatment center. Patients will be asked to come to the Narcotic Treatment Center for one 12-lead ECG Specific Aim 2: QTc intervals from ECGs generated by the AliveCor® heart monitor will be compared prospectively to simultaneous twelve lead ECGs for validation purposes in the methadone-treated patients in a narcotic treatment center.

Methadone-induced QTc interval prolongation; Methadone-treated patients, no QT interval prolongation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing methadone treatment for addiction in a narcotic treatment center

You may qualify if:

• Patients enrolled in the Eskenazi Health Midtown Narcotic Treatment Center between August 1, 2014 - December 31, 2016
• years and older

You may not qualify if:

• Documented history by prescriber or baseline prolonged QTc interval
• Patients with insufficient information in the electronic health record
• Incarceration

Sponsors & Collaborators

• Indiana University: lead
• Purdue University: collaborator

Study Sites (1)

Eskenazi Health

Indianapolis, Indiana, 46202, United States

Location

Related Publications (2)

• Titus-Lay EN, Jaynes HA, Tomaselli Muensterman E, Ott CA, Walroth TA, Williams G, Moe PR, Wilbrandt M, Tisdale JE. Accuracy of a single-lead mobile smartphone electrocardiogram for QT interval measurement in patients undergoing maintenance methadone therapy. Pharmacotherapy. 2021 Jun;41(6):494-500. doi: 10.1002/phar.2521. Epub 2021 Apr 19.

  PMID: 33772822 DERIVED

• Titus-Lay EN, Jaynes HA, Tomaselli Muensterman E, Walroth TA, Ott CA, Desta Z, Williams G, Moe PR, Wilbrandt M, Tisdale JE. Methadone-associated QT interval prolongation in patients undergoing maintenance therapy in an urban opioid treatment program. Pharmacotherapy. 2021 Mar;41(3):238-246. doi: 10.1002/phar.2498. Epub 2021 Feb 2.

  PMID: 33345336 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples for determination of cytochrome P-450 2B6 genotype

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Adjunct Professor

Study Record Dates

• First Submitted: September 8, 2016
• First Posted: September 13, 2016
• Study Start: November 1, 2016
• Primary Completion: May 22, 2018
• Study Completion: May 22, 2018
• Last Updated: July 8, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)