Integrating Pharmacogenetics In Clinical Care

Cardiovascular Disease Clinical Trial

— I-PICC  

Official title:

Clinical Safety and Efficacy of Pharmacogenetics in Veteran Care

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02871934
• Other study ID #: SPLC-006-15S
• Secondary ID: IK2CX001262
• Status: Completed
• Phase: N/A
• Start date: August 1, 2016
• Est. completion date: December 31, 2020

Study information

• Verified date: February 2022
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 408
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases

Intervention

Genetic:
• SLCO1B1 Genotype
Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.

Locations

Country	Name	City	State
United States	VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

References & Publications (2)

Vassy JL, Brunette CA, Majahalme N, Advani S, MacMullen L, Hau C, Zimolzak AJ, Miller SJ. The Integrating Pharmacogenetics in Clinical Care (I-PICC) Study: Protocol for a point-of-care randomized controlled trial of statin pharmacogenetics in primary care. Contemp Clin Trials. 2018 Dec;75:40-50. doi: 10.1016/j.cct.2018.10.010. Epub 2018 Oct 24. — View Citation

Vassy JL, Gaziano JM, Green RC, Ferguson RE, Advani S, Miller SJ, Chun S, Hage AK, Seo SJ, Majahalme N, MacMullen L, Zimolzak AJ, Brunette CA. Effect of Pharmacogenetic Testing for Statin Myopathy Risk vs Usual Care on Blood Cholesterol: A Randomized Clin — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Participant Response Distributions to Belief in Medications Questionnaire at 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
Other	Number of Participants Recalling Pharmacogenetic Testing at 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
Other	Number of Participants Reporting Statin-related Muscle Side Effects at 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
Primary	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	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
Secondary	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
Secondary	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