Preemptive Pharmacogenetic-guided Metoprolol Management for PostoperativeAtrial Fibrillation in Cardiac Surgery (PREEMPTIVE)

Preemptive Pharmacogenetic- Guided Metoprolol Management for Postoperative Atrial Fibrillation in Cardiac Surgery: The PREEMPTIVE- Pilot Trial

Metoprolol is frequently administered to cardiac surgery patients to reduce the incidence of postoperative atrial fibrillation (PoAF). Metoprolol is metabolized by the enzyme CYP2D6, which is known to have many mutations that could influence a patient's ability to metabolize the drug. In this prospective clinical trial, the investigators will determine the genotype of CYP2D6 for patients undergoing cardiac surgery, provide an altered dosing recommendation for metoprolol, then report the relative effectiveness in managing PoAF for each pharmacogenetic- guided dosing category. The investigators will also explore the effects of personalized metoprolol dosing recommendations on outcomes in hospital length of stay, cost, and provider participation.

Study Overview

• Status: Completed
• Conditions: Post-operative Atrial Fibrillation
• Intervention / Treatment: Other: Guided Metoprolol Management

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age greater than or equal to 18 years
• Scheduled for surgical procedure (coronary artery bypass graft and/or valve repair/replacement) at Vanderbilt University Medical Center

Exclusion Criteria:

• History of allergic reactions or contraindications to beta-blockers
• Patients with persistent atrial fibrillation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pharmacogenetic-guided metoprolol management

Other: Guided Metoprolol Management; CYP2D6 Genotyping: Consented patients will have blood drawn for genotyping prior to surgery. Patients will be classified as poor metabolizers, intermediate metabolizers, extensive (normal) metabolizers, or ultrafast metabolizers. Pharmacogenetic- Guided Metoprolol Management: A best practice advisory will be integrated into institutional clinical decision support systems for metoprolol dosing based on metabolic status of each patient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of post-operative atrial fibrillation	Incidence of post-operative atrial fibrillation measured with post-operative electrocardiogram or rhythm strip, or at least two of the following: documentation in the progress notes, nursing notes, discharge summary, and change in medication.	From the end of anesthesia up to hospital discharge; usually 3-4 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of genome tailored prescription changes	Rate of genome tailored prescription changes as measured by the proportion of patients in whom metoprolol prescription is based on CYP2D6 metabolizer status.	From the end of anesthesia up to hospital discharge; usually 3-4 days
Length of hospital stay	Length of hospital stay (in days) after surgery	From end of surgery to hospital discharge; usually 3-4 days
Overall cost of treatment		From end of surgery to hospital discharge; usually 3-4 days
Cost of interventions to control or treat post-operative atrial fibrillation		From end of anesthesia to hospital discharge; usually 3-4 days
Incidence of adverse drug events		From end of anesthesia to hospital discharge; usually 3-4 days
Proportion of clinical decision support tool recommendations that were acknowledged and accepted by provider		From end of anesthesia to hospital discharge; usually 3-4 days
Proportion of clinical decision support tool recommendations that were acknowledged but ignored by the provider.		From end of anesthesia to hospital discharge; usually 3-4 days
Reasons for non-adherence to recommendations	Reasons for non-adherence to recommendations; prepopulated choices including 1. clinically inappropriate recommendation 2. provider preference 3. Other (free text option).	From end of anesthesia to hospital discharge; usually 3-4 days

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Principal Investigator: Miklos Kertai, MD. PhD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2021
• Primary Completion (Actual): October 24, 2022
• Study Completion (Actual): November 20, 2022

Study Registration Dates

• First Submitted: May 7, 2019
• First Submitted That Met QC Criteria: May 7, 2019
• First Posted (Actual): May 9, 2019

Study Record Updates

• Last Update Posted (Estimate): March 10, 2023
• Last Update Submitted That Met QC Criteria: March 7, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Genotype; Phenotype; CYP2D6; Metoprolol
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Metoprolol
• Other Study ID Numbers: 190578

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No