Dataset Information

CYP2D6 Genotype-guided Metoprolol Therapy in Cardiac Surgery Patients: Rationale and Design of the Pharmacogenetic-guided Metoprolol Management for Postoperative Atrial Fibrillation in Cardiac Surgery (PREEMPTIVE) Pilot Study.

ABSTRACT:

Objectives

The Preemptive Pharmacogenetic-guided Metoprolol Management for Atrial Fibrillation in Cardiac Surgery (PREEMPTIVE) pilot trial aims to use existing institutional resources to develop a process for integrating CYP2D6 pharmacogenetic test results into the patient electronic health record, to develop an evidence-based clinical decision support tool to facilitate CYP2D6 genotype-guided metoprolol administration in the cardiac surgery setting, and to determine the impact of implementing this CYP2D6 genotype-guided integrated approach on the incidence of postoperative atrial fibrillation (AF), provider, and cost outcomes.

Design

One-arm Bayesian adaptive design clinical trial.

Setting

Single center, university hospital.

Participants

The authors will screen (including CYP2D6 genotype) up to 600 (264 ± 144 expected under the adaptive design) cardiac surgery patients, and enroll up to 200 (88 ± 48 expected) poor, intermediate, and ultrarapid CYP2D6 metabolizers over a period of 2 years at a tertiary academic center.

Interventions

All consented and enrolled patients will receive the intervention of CYP2D6 genotype-guided metoprolol management based on CYP2D6 phenotype classified as a poor, intermediate, extensive (normal), or ultrarapid metabolizer.

Measurements and main results

The primary outcome will be the incidence of postoperative AF. Secondary outcomes relating to rates of CYP2D6 genotype-guided prescription changes, costs, lengths of stay, and implementation metrics also will be investigated.

Conclusions

The PREEMPTIVE pilot study is the first perioperative pilot trial to provide essential information for the design of a future, large-scale trial comparing CYP2D6 genotype-guided metoprolol management with a nontailored strategy in terms of managing AF. In addition, secondary outcomes regarding implementation, clinical benefit, safety, and cost-effectiveness in patients undergoing cardiac surgery will be examined.

SUBMITTER: Dunham WC

PROVIDER: S-EPMC6911825 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CYP2D6 Genotype-guided Metoprolol Therapy in Cardiac Surgery Patients: Rationale and Design of the Pharmacogenetic-guided Metoprolol Management for Postoperative Atrial Fibrillation in Cardiac Surgery (PREEMPTIVE) Pilot Study.

Dunham Wills C WC Weinger Matthew B MB Slagle Jason J Pretorius Mias M Shah Ashish S AS Absi Tarek S TS Shotwell Matthew S MS Beller Marc M Thomas Erica E Vnencak-Jones Cindy L CL Freundlich Robert E RE Wanderer Jonathan P JP Sandberg Warren S WS Kertai Miklos D MD

Journal of cardiothoracic and vascular anesthesia 20190910 1

<h4>Objectives</h4>The Preemptive Pharmacogenetic-guided Metoprolol Management for Atrial Fibrillation in Cardiac Surgery (PREEMPTIVE) pilot trial aims to use existing institutional resources to develop a process for integrating CYP2D6 pharmacogenetic test results into the patient electronic health record, to develop an evidence-based clinical decision support tool to facilitate CYP2D6 genotype-guided metoprolol administration in the cardiac surgery setting, and to determine the impact of implem ...[more]

PMID: 31606278

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Project description:Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery. It has been proven to be associated with an increase in the incidence of early complications and mortality, an increase in the rate of hospital stay duration, and economic costs of their treatment. One of the pharmaceutical drugs recommended by the American College of Cardiology (ACC)/American Heart Association (AHA) for preventing POAF is colchicine (class IIB). However, the results of research on the efficacy and safety of colchicine are ambiguous and, consequently, require further study. Evaluating the efficacy of short-term colchicine administration in the prevention of POAF in patients after open-heart surgery. Double-blind, randomized, placebo-controlled clinical trial. The subjects were randomly assigned to two groups: treatment group (n = 50) with subjects receiving 1 mg of colchicine 24 h before the surgery, as well as on days 2, 3, 4, and 5 in the postoperative period; and the control group (n = 51), receiving placebo on the same schedule. The primary endpoint was the frequency of POAF in both groups within 7 days after surgery. The study included 101 patients (82 men, 19 women). Baseline clinical, laboratory, instrumental, and intraoperative data did not differ statistically significantly between the groups. POAF was detected in 9 patients (18%) of the treatment group and 15 subjects (29.4%) of the control group, which had no statistical significance (odds ratio, OR 0.527; 95% Cl 0.206-1.349; p = 0.178). No statistically significant differences were revealed for most secondary endpoints, as well as between the groups for all laboratory parameters. There were statistically significant differences between the groups solely in the frequency of diarrhea: 16 (32%) patients in the treatment group and 6 (11.8%) subjects in the control group (OR 3.529; 95% Cl 1.249-9.972; p = 0.010). We did not detect any statistical differences between the groups in terms of primary endpoints, which could be due to the insufficient volume of the sample of the study. However, we detected some trends of statistical differences among the groups in terms of some parameters. Unique identifier: NCT04224545.

Dataset Information

CYP2D6 Genotype-guided Metoprolol Therapy in Cardiac Surgery Patients: Rationale and Design of the Pharmacogenetic-guided Metoprolol Management for Postoperative Atrial Fibrillation in Cardiac Surgery (PREEMPTIVE) Pilot Study.

Objectives

Design

Setting

Participants

Interventions

Measurements and main results

Conclusions

Publications

CYP2D6 Genotype-guided Metoprolol Therapy in Cardiac Surgery Patients: Rationale and Design of the Pharmacogenetic-guided Metoprolol Management for Postoperative Atrial Fibrillation in Cardiac Surgery (PREEMPTIVE) Pilot Study.

Similar Datasets

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