Clinical trial NCT02871934: Integrating Pharmacogenetics In Clinical Care
Official title: Clinical Safety and Efficacy of Pharmacogenetics in Veteran Care
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Disease
Keywords: Pharmacogenetics
SLCO1B1 protein, human
OATP1B1 protein, human
Simvastatin
Cardiovascular disease
Cholesterol
Statin-related myotoxicity
Veterans
Point-of-care
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2016-08-18
Enrollment: 408
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: 12-Month Change in LDL Cholesterol
timeFrame: 12 months
Secondary outcomes:
measure: Number of Participants With an American College of Cardiology/American Heart Association (ACC/AHA) Guideline Concordant Statin Prescription at 12 Months
timeFrame: 12 months
measure: Number of Participants With Chart Review Documented Statin-related Myotoxicity at 12 Months
timeFrame: 12 months
measure: Number of Participants Meeting Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Safe Simvastatin Prescription at 12 Months
timeFrame: 12 months
Other outcomes:
measure: Participant Response Distributions to Belief in Medications Questionnaire at 12 Months
timeFrame: 12 months
measure: Number of Participants Recalling Pharmacogenetic Testing at 12 Months
timeFrame: 12 months
measure: Number of Participants Reporting Statin-related Muscle Side Effects at 12 Months
timeFrame: 12 months
Locations:
city: Boston
country: United States
facility: VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
state: Massachusetts
Study officials:
affiliation: VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
name: Jason L Vassy, MD MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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 Clinical Trial. JAMA Netw Open. 2020 Dec 1;3(12):e2027092. doi: 10.1001/jamanetworkopen.2020.27092.
citation: Brunette CA, Miller SJ, Majahalme N, Hau C, MacMullen L, Advani S, Ludin SA, Zimolzak AJ, Vassy JL. Pragmatic Trials in Genomic Medicine: The Integrating Pharmacogenetics In Clinical Care (I-PICC) Study. Clin Transl Sci. 2020 Mar;13(2):381-390. doi: 10.1111/cts.12723. Epub 2019 Dec 18.