I-PICC: Integrating Pharmacogenetics In Clinical Care

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT02871934
• Collaborator: (none)
• Enrollment: 408
• Location: 1
• Arms: 2
• Actual Duration (Months): 53
• Patients Per Site Per Month: 7.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Disease	Genetic: SLCO1B1 Genotype	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 408 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Diagnostic
• Official Title: Clinical Safety and Efficacy of Pharmacogenetics in Veteran Care
• Actual Study Start Date: Aug 1, 2016
• Actual Primary Completion Date: Dec 31, 2020
• Actual Study Completion Date: Dec 31, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 12-Month Change in LDL Cholesterol [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.

Secondary Outcome Measures

1. Number of Participants With an American College of Cardiology/American Heart Association (ACC/AHA) Guideline Concordant Statin Prescription at 12 Months [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.

2. Number of Participants With Chart Review Documented Statin-related Myotoxicity at 12 Months [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.

3. Number of Participants Meeting Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Safe Simvastatin Prescription at 12 Months [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.

Other Outcome Measures

1. Participant Response Distributions to Belief in Medications Questionnaire at 12 Months [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."

2. Number of Participants Recalling Pharmacogenetic Testing at 12 Months [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.

3. Number of Participants Reporting Statin-related Muscle Side Effects at 12 Months [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA	Boston	Massachusetts	United States	02130

Sponsors and Collaborators

• VA Office of Research and Development

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 28, 2019

More Information

Publications

• 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.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT02871934
• Other Study ID Numbers: SPLC-006-15S; IK2CX001262
• First Posted: Aug 18, 2016
• Last Update Posted: Feb 21, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by VA Office of Research and Development: Pharmacogenetics; SLCO1B1 protein, human; OATP1B1 protein, human; Simvastatin; Cardiovascular disease; Cholesterol; Statin-related myotoxicity; Veterans; Point-of-care
• Additional relevant MeSH terms: Cardiovascular Diseases

Study Results

Participant Flow

Arm/Group Title	PGx+	PGx-
Arm/Group Description	Patients in the PGx+ (intervention) arm will have their SLCO1B1 results reported to their ordering provider immediately. SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.	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). SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.
Period Title: Overall Study
STARTED	193	215
COMPLETED	193	215
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	PGx+	PGx-	Total
Arm/Group Description	Patients in the PGx+ (intervention) arm will have their SLCO1B1 results reported to their ordering provider immediately. SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.	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). SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.	Total of all reporting groups
Overall Participants	193	215	408
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.2 (7.8)	63.9 (7.7)	64.1 (7.8)
Sex: Female, Male (Count of Participants)
Female	9 4.7%	16 7.4%	25 6.1%
Male	184 95.3%	199 92.6%	383 93.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 1%	6 2.8%	8 2%
Not Hispanic or Latino	187 96.9%	208 96.7%	395 96.8%
Unknown or Not Reported	4 2.1%	1 0.5%	5 1.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.5%	0 0%	1 0.2%
Asian	1 0.5%	0 0%	1 0.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	25 13%	25 11.6%	50 12.3%
White	156 80.8%	185 86%	341 83.6%
More than one race	3 1.6%	1 0.5%	4 1%
Unknown or Not Reported	7 3.6%	4 1.9%	11 2.7%
Region of Enrollment (Count of Participants)
United States	193 100%	215 100%	408 100%
Smokers (Count of Participants)
Count of Participants [Participants]	59 30.6%	78 36.3%	137 33.6%
Meeting ACC/AHA Criteria for Statin Therapy (Count of Participants)
ASCVD	52 26.9%	46 21.4%	98 24%
LDL-C > 190 mg/dL	5 2.6%	6 2.8%	11 2.7%
Diabetes	47 24.4%	51 23.7%	98 24%
10-year ASCVD risk >= 7.5%	171 88.6%	196 91.2%	367 90%
SLCO1B1 Genotype (Count of Participants)
Normal function (T/T)	148 76.7%	140 65.1%	288 70.6%
Decrease function (T/C)	40 20.7%	70 32.6%	110 27%
Poor function (C/C)	5 2.6%	5 2.3%	10 2.5%

Outcome Measures

1. Primary Outcome

Title	12-Month Change in LDL Cholesterol
Description	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.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PGx+	PGx-
Arm/Group Description	Patients in the PGx+ (intervention) arm will have their SLCO1B1 results reported to their ordering provider immediately. SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.	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). SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.
Measure Participants	193	215
Mean (Standard Error) [mg/dL]	-1.1 (1.2)	-2.2 (1.3)

2. Secondary Outcome

Title	Number of Participants With an American College of Cardiology/American Heart Association (ACC/AHA) Guideline Concordant Statin Prescription at 12 Months
Description	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.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PGx+	PGx-
Arm/Group Description	Patients in the PGx+ (intervention) arm will have their SLCO1B1 results reported to their ordering provider immediately. SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.	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). SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.
Measure Participants	193	215
Count of Participants [Participants]	12 6.2%	14 6.5%

3. Secondary Outcome

Title	Number of Participants With Chart Review Documented Statin-related Myotoxicity at 12 Months
Description	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.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PGx+	PGx-
Arm/Group Description	Patients in the PGx+ (intervention) arm will have their SLCO1B1 results reported to their ordering provider immediately. SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.	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). SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.
Measure Participants	193	215
Count of Participants [Participants]	2 1%	3 1.4%

4. Secondary Outcome

Title	Number of Participants Meeting Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Safe Simvastatin Prescription at 12 Months
Description	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.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PGx+	PGx-
Arm/Group Description	Patients in the PGx+ (intervention) arm will have their SLCO1B1 results reported to their ordering provider immediately. SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.	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). SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.
Measure Participants	193	215
Count of Participants [Participants]	193 100%	215 100%

5. Other Pre-specified Outcome

Title	Participant Response Distributions to Belief in Medications Questionnaire at 12 Months
Description	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."
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Data analyzed only for patients who completed the 12-month end-of-study survey.

Arm/Group Title	PGx+	PGx-
Arm/Group Description	Patients in the PGx+ (intervention) arm will have their SLCO1B1 results reported to their ordering provider immediately. SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.	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). SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.
Measure Participants	169	203
Strongly agree	28 14.5%	30 14%
Agree	65 33.7%	84 39.1%
Uncertain	29 15%	37 17.2%
Disagree	29 15%	40 18.6%
Strongly disagree	17 8.8%	12 5.6%
Strongly agree	9 4.7%	10 4.7%
Agree	26 13.5%	20 9.3%
Uncertain	46 23.8%	56 26%
Disagree	63 32.6%	89 41.4%
Strongly disagree	24 12.4%	28 13%

6. Other Pre-specified Outcome

Title	Number of Participants Recalling Pharmacogenetic Testing at 12 Months
Description	Assessed by phone survey 12 months after enrollment. Whether patient remembers receiving PGx results from provider and, if so, remembers the results and interpretation.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Result recall only assessed in intervention arm participants. Control participants received results 12 months after enrollment.

Arm/Group Title	PGx+
Arm/Group Description	Patients in the PGx+ (intervention) arm will have their SLCO1B1 results reported to their ordering provider immediately. SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.
Measure Participants	169
Count of Participants [Participants]	11 5.7%

7. Other Pre-specified Outcome

Title	Number of Participants Reporting Statin-related Muscle Side Effects at 12 Months
Description	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.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Data analyzed only for patients who completed the 12-month end-of-study survey.

Arm/Group Title	PGx+	PGx-
Arm/Group Description	Patients in the PGx+ (intervention) arm will have their SLCO1B1 results reported to their ordering provider immediately. SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.	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). SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.
Measure Participants	169	203
Count of Participants [Participants]	3 1.6%	3 1.4%

Adverse Events

Time Frame	12 months
Adverse Event Reporting Description	Mortality and adverse event data collected non-systematically due to minimal risk nature of the trial intervention. Most mortality events discovered when attempting to reach patient for end-of-study survey. Any participant death or adverse event discovered by study staff during the observation period or via attempts to make contact for end-of-study survey (per protocol, contacts occurred up to 3 months after end of 12-month observation period) data collection are reported.
Arm/Group Title	PGx+		PGx-
Arm/Group Description	Patients in the PGx+ (intervention) arm will have their SLCO1B1 results reported to their ordering provider immediately. SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.		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). SLCO1B1 Genotype: Polymerase chain reaction (PCR) assay for SLCO1B1 rs4149056, with possible results T/T, T/C, or C/C.
All Cause Mortality
	PGx+		PGx-
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/193 (4.1%)		5/215 (2.3%)
Serious Adverse Events
	PGx+		PGx-
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/193 (0%)		0/215 (0%)
Other (Not Including Serious) Adverse Events
	PGx+		PGx-
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/193 (0%)		0/215 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.