Integrating Pharmacogenetics In Clinical Care (I-PICC)

February 17, 2022 updated by: VA Office of Research and Development

Clinical Safety and Efficacy of Pharmacogenetics in Veteran Care

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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).

Study Type

Interventional

Enrollment (Actual)

408

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02130
        • VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PGx+
Patients in the PGx+ (intervention) arm will have their SLCO1B1 results reported to their ordering provider immediately.
Genetic: SLCO1B1 Genotype
Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.
Other Names:
  • SLCO1B1 Pharmacogenetic Test
Experimental: PGx-
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
Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.
Other Names:
  • SLCO1B1 Pharmacogenetic Test

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
12-Month Change in LDL Cholesterol
Time Frame: 12 months
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
Time Frame: 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
Time Frame: 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
Time Frame: 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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Participant Response Distributions to Belief in Medications Questionnaire at 12 Months
Time Frame: 12 months
Assessed by phone survey 12 months after enrollment. Consists of 2 items: "Do you agree or disagree with these statements?: "My health in the future will depend on my medicines" and "Medicines do more harm than good."
12 months
Number of Participants Recalling Pharmacogenetic Testing at 12 Months
Time Frame: 12 months
Assessed by phone survey 12 months after enrollment. Whether patient remembers receiving PGx results from provider and, if so, remembers the results and interpretation.
12 months
Number of Participants Reporting Statin-related Muscle Side Effects at 12 Months
Time Frame: 12 months
Assessed by phone survey 12 months after enrollment. Whether patient attributes muscle pains, weakness, or cramps to a statin taken in the prior 12 months.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Investigators

  • Principal Investigator: Jason L Vassy, MD MPH, VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2016

Primary Completion (Actual)

December 31, 2020

Study Completion (Actual)

December 31, 2020

Study Registration Dates

First Submitted

August 16, 2016

First Submitted That Met QC Criteria

August 16, 2016

First Posted (Estimate)

August 18, 2016

Study Record Updates

Last Update Posted (Actual)

February 21, 2022

Last Update Submitted That Met QC Criteria

February 17, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SPLC-006-15S
  • IK2CX001262 (U.S. NIH Grant/Contract)

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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