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Methadone-Induced QT Interval Prolongation in a Narcotic Treatment Center

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ClinicalTrials.gov Identifier: NCT02898337
Recruitment Status : Recruiting
First Posted : September 13, 2016
Last Update Posted : August 7, 2018
Sponsor:
Collaborator:
Purdue University
Information provided by (Responsible Party):
James E. Tisdale, Indiana University

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.


Condition or disease Intervention/treatment
QT Interval Prolongation Device: AliveCor handheld mobile ECG

  Show Detailed Description

Study Type : Observational
Estimated Enrollment : 170 participants
Observational Model: Cohort
Time Perspective: Other
Official Title: Methadone-Induced QT Interval Prolongation in a Narcotic Treatment Center: Identifying Patients at Risk and Simplifying ECG Monitoring
Actual Study Start Date : November 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Methadone-induced QTc interval prolongation Device: AliveCor handheld mobile ECG

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-treated patients, no QT interval prolongation Device: AliveCor handheld mobile ECG

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.





Primary Outcome Measures :
  1. QTc interval prolongation [ Time Frame: 6 weeks ]

Biospecimen Retention:   Samples With DNA
Blood samples for determination of cytochrome P-450 2B6 genotype


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients undergoing methadone treatment for addiction in a narcotic treatment center
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02898337


Contacts
Contact: James E Tisdale, PharmD 317-880-5418 jtisdale@purdue.edu
Contact: Heather A Jaynes, MSN 317-880-5410 hwroblew@iu.edu

Locations
United States, Indiana
Eskenazi Health Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Paul Moe, MD    317-788-6560    paul.moe@eskenazihealth.edu   
Sponsors and Collaborators
Indiana University
Purdue University

Responsible Party: James E. Tisdale, Adjunct Professor, Indiana University
ClinicalTrials.gov Identifier: NCT02898337     History of Changes
Other Study ID Numbers: 1608001774
First Posted: September 13, 2016    Key Record Dates
Last Update Posted: August 7, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Methadone
Narcotics
Analgesics, Opioid
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antitussive Agents
Respiratory System Agents