Integrating Pharmacogenetics In Clinical Care

Study Overview
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Brief Summary
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This study will determine whether using a genetic test (for the SLCO1B1 gene) can help patients and providers choose the right type and dose of cholesterol-lowering statin medications to lower the risk of cardiovascular disease, while minimizing the muscle pain side effects that sometimes occur with statins.

Detailed Description
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Variants at rs4149056 in the SLCO1B1 gene are associated with a greater risk of simvastatin-related myopathy. Despite the growing implementation of SLCO1B1 rs4149056 genotyping in health systems across the United States, there is little randomized controlled trial data on the impact of SLCO1B1 testing on clinical outcomes. The IPICC Study will use a randomized design to determine the impact of the clinical integration of SLCO1B1 genotype testing on important patient outcomes, including statin prescribing, LDL cholesterol, and statin-related myopathy. In addition, by enrolling statin-naive patients with a recent cholesterol panel, this trial will capture a moment of clinical decision-making when SLCO1B1 rs4149056 genotype might be most clinically relevant. This randomized-control trial has two primary aims: Aim 1 (Drug safety): To determine the impact of SLCO1B1 pharmacogenetic testing on concordance with Clinical Pharmacogenetics Implementation Consortium (CPIC) pharmacogenetic guidelines for safe simvastatin prescribing and on the incidence of statin-related myopathy in VA (drug safety). Aim 2 (Cardiovascular disease, CVD, prevention): To determine the impact of SLCO1B1 pharmacogenetic testing on LDL cholesterol levels and concordance with CVD prevention guidelines. The I-PICC Study is enrolling 408 statin-naive primary care and women's health patients across the Veteran Affairs Boston Healthcare System. Eligible patients are aged 40-75 and have elevated risk of cardiovascular disease (CVD) according to American College of Cardiology/American Heart Association (ACC/AHA) guidelines. Primary care providers (PCPs) are also research subjects and consent via electronic health record (EHR) alerts. To model pharmacogenotyping at the point of care, the investigators are enrolling patients with recent cholesterol results when their PCPs order laboratory testing, indicating a moment of clinical decision-making about CVD risk. Enrolled patients are randomized to have their PCPs receive results through the EHR immediately (PGx+) vs. after 1 year (PGx-). The investigators will query clinical and pharmacy data for 1-year outcomes: myopathy and concordance with CPIC simvastatin guidelines (drug safety) and cholesterol levels and concordance with ACC/AHA guidelines (CVD risk reduction).

Official Title
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Clinical Safety and Efficacy of Pharmacogenetics in Veteran Care

Conditions
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Cardiovascular Disease

Intervention / Treatment
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* Genetic: SLCO1B1 Genotype


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Providers: All providers in Primary Care and Women's Health at VA Boston Healthcare System will be eligible to participate. Patients: Aged 40-75 years Have no history of statin use Have received VA care for at least the prior 6 months Are a patient of an enrolled provider Meet at least 1 of the following criteria: cardiovascular disease (CVD) diabetes LDL cholesterol value >= 190 mg/dL 10-year CVD risk of 7.5%, calculated with the ACC/AHA 2013 pooled risk equations Exclusion Criteria: Patients will be ineligible if they: Do not meet the inclusion criteria Pregnant Incarcerated or institutionalized

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PGx+<br>Patients in the PGx+ (intervention) arm will have their SLCO1B1 results reported to their ordering provider immediately. | Genetic: SLCO1B1 Genotype<br>* Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.<br>* Other names: SLCO1B1 Pharmacogenetic Test;|
| Experimental: PGx-<br>Patient in the PGx- (control) arm will have their SLCO1B1 results reported to their ordering provider at the end of the study (after 12 months). | Genetic: SLCO1B1 Genotype<br>* Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.<br>* Other names: SLCO1B1 Pharmacogenetic Test;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12-Month Change in LDL Cholesterol | The primary CVD prevention outcome is 12-month change in low-density lipoprotein (LDL) cholesterol, defined as LDL value at 12 months minus LDL value at baseline. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With an American College of Cardiology/American Heart Association (ACC/AHA) Guideline Concordant Statin Prescription at 12 Months | In 2013, the ACC/AHA endorsed guidelines that recommended prescribing statins of specific intensities (moderate or high) for distinct populations. Using patient characteristics and prescription data, the investigators will generate a 2-level CVD prevention outcome (concordant vs. non-concordant) for each participant, a measure of whether a patient's statin prescription is adequate for his/her level of CVD risk. | 12 months | 
| Number of Participants With Chart Review Documented Statin-related Myotoxicity at 12 Months | Chart review of all patient notes during the 12 months after enrollment will be used to determine the proportion of patients in each arm who experienced statin-related muscle side effects during the observation period. | 12 months | 
| Number of Participants Meeting Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Safe Simvastatin Prescription at 12 Months | Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines recommend specific simvastatin doses when a patient's SLCO1B1 genotype is known. The investigators will compare each patient's medication prescriptions one year after enrollment to this guideline to generate a 2-level safety outcome (potentially safe vs. potentially unsafe simvastatin prescription) for each participant. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacogenetics, SLCO1B1 protein, human, OATP1B1 protein, human, Simvastatin, Cardiovascular disease, Cholesterol, Statin-related myotoxicity, Veterans, Point-of-care