Trial Outcomes & Findings for Genetically Guided Statin Therapy (NCT NCT01894230)

NCT ID: NCT01894230

Last Updated: 2017-06-23

Results Overview

The Morisky Medication Adherence Scale (MMAS) is a self-reported measure of adherence, collected at baseline for general medication and at 3 and 8 months of followup for statin specific adherence. The eight-item MMAS survey will be used. This is a modified version of the original four-item MMAS capturing further aspects of adherence behavior. The survey includes 8 yes/no items that are summed to create an overall adherence score ranging from of 0 to 8, with higher scores indicating better adherence. The primary hypothesis is that the genetically guided statin therapy leads to greater adherence of statin therapy, corresponding to a higher MMAS score.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 167 participants
• Primary outcome timeframe: 3 months and 8 months
• Results posted on: 2017-06-23

Participant Flow

Eight participants that signed a consent either withdrew consent, were lost-to follow up, or were screen-failures and thus were not randomized.

Participant milestones

Measure	Genotype Results Plus Usual Care * Genetic testing for SLCO1B1\*5 allele * Reporting for SLCO1B1\*5 allele at randomization Reporting for SLCO1B1\*5 allele at randomization: Reporting of genetic test results to patient and provider at randomization Genetic testing for SLCO1B1\*5 allele: Blood test for SLCO1B1\*5 allele	Usual Care Only * Genetic testing for SLCO1B1\*5 allele * Reporting for SLCO1B1\*5 allele at the end of study Reporting for SLCO1B1\*5 allele at the end: Usual care recommendations provided to patient and provider at randomization. Genotyping results provided at the end of study. Genetic testing for SLCO1B1\*5 allele: Blood test for SLCO1B1\*5 allele
Overall Study STARTED	83	76
Overall Study COMPLETED	76	69
Overall Study NOT COMPLETED	7	7

Reasons for withdrawal

Measure	Genotype Results Plus Usual Care * Genetic testing for SLCO1B1\*5 allele * Reporting for SLCO1B1\*5 allele at randomization Reporting for SLCO1B1\*5 allele at randomization: Reporting of genetic test results to patient and provider at randomization Genetic testing for SLCO1B1\*5 allele: Blood test for SLCO1B1\*5 allele	Usual Care Only * Genetic testing for SLCO1B1\*5 allele * Reporting for SLCO1B1\*5 allele at the end of study Reporting for SLCO1B1\*5 allele at the end: Usual care recommendations provided to patient and provider at randomization. Genotyping results provided at the end of study. Genetic testing for SLCO1B1\*5 allele: Blood test for SLCO1B1\*5 allele
Overall Study Lost to Follow-up	2	2
Overall Study Withdrawal by Subject	4	4
Overall Study Non-adherent	0	1
Overall Study Death	1	0

Baseline Characteristics

Genetically Guided Statin Therapy

Baseline characteristics by cohort

Measure	Genotype Results Plus Usual Care n=83 Participants * Genetic testing for SLCO1B1\*5 allele * Reporting for SLCO1B1\*5 allele at randomization Reporting for SLCO1B1\*5 allele at randomization: Reporting of genetic test results to patient and provider at randomization Genetic testing for SLCO1B1\*5 allele: Blood test for SLCO1B1\*5 allele	Usual Care Only n=76 Participants * Genetic testing for SLCO1B1\*5 allele * Reporting for SLCO1B1\*5 allele at the end of study Reporting for SLCO1B1\*5 allele at the end: Usual care recommendations provided to patient and provider at randomization. Genotyping results provided at the end of study. Genetic testing for SLCO1B1\*5 allele: Blood test for SLCO1B1\*5 allele	Total n=159 Participants Total of all reporting groups
Age, Continuous	62.7 years STANDARD_DEVIATION 10.2 • n=5 Participants	62.5 years STANDARD_DEVIATION 11.5 • n=7 Participants	62.6 years STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	50 Participants n=7 Participants	91 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	26 Participants n=7 Participants	68 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · White	66 Participants n=5 Participants	61 Participants n=7 Participants	127 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Black/African American	14 Participants n=5 Participants	11 Participants n=7 Participants	25 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Other	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment United States	83 participants n=5 Participants	76 participants n=7 Participants	159 participants n=5 Participants

PRIMARY outcome

Timeframe: 3 months and 8 months

Population: Only participants who re-initiated statin use were eligible to do statin specific MMAS and included in the analysis.

The Morisky Medication Adherence Scale (MMAS) is a self-reported measure of adherence, collected at baseline for general medication and at 3 and 8 months of followup for statin specific adherence. The eight-item MMAS survey will be used. This is a modified version of the original four-item MMAS capturing further aspects of adherence behavior. The survey includes 8 yes/no items that are summed to create an overall adherence score ranging from of 0 to 8, with higher scores indicating better adherence. The primary hypothesis is that the genetically guided statin therapy leads to greater adherence of statin therapy, corresponding to a higher MMAS score.

Outcome measures

Measure	Genotype Results Plus Usual Care n=37 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at randomization	Usual Care Only n=25 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at the end of study
Morisky Medication Adherence Scale (MMAS) Score MMAS Score 3 Months	6.8 units on a scale Standard Deviation 1.5	6.9 units on a scale Standard Deviation 1.6
Morisky Medication Adherence Scale (MMAS) Score MMAS Score 8 Months	6.8 units on a scale Standard Deviation 1.7	7.1 units on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: Baseline, Month 3, Month 8

Population: All subjects with available data were included in the analysis.

The continuous outcomes LDLc will be modeled as a linear regression with arm and baseline LDL as predictors.

Outcome measures

Measure	Genotype Results Plus Usual Care n=83 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at randomization	Usual Care Only n=76 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at the end of study
Low Density Lipoprotein Cholesterol (LDLc) at Baseline, Month 3 and Month 8 Baseline LDLc	152.7 mg/dL Standard Deviation 41.1	157.6 mg/dL Standard Deviation 41.9
Low Density Lipoprotein Cholesterol (LDLc) at Baseline, Month 3 and Month 8 Month 3 LDLc	131.9 mg/dL Standard Deviation 42	144.4 mg/dL Standard Deviation 43
Low Density Lipoprotein Cholesterol (LDLc) at Baseline, Month 3 and Month 8 Month 8 LDLc	128.6 mg/dL Standard Deviation 37.9	141 mg/dL Standard Deviation 44.4

SECONDARY outcome

Timeframe: Baseline to Last patient follow-up in study (3 months or 8 months)

Population: Only subjects who re-initiated statin medication and reported statin medication refills were included in the analysis.

Medication possession ratio will be calculated based on number of statin medication refills over time from randomization to end of follow up. MPR is calculated as follows: 1.Sum of the days' supply of all statin medications is the sum of the number of pills dispensed for each statin prescription during follow up (taken from 3-month, 4-month and 8-month statin utilization review) 2.Sum of the days of follow up = date of 8-month follow up survey - date of randomization 3.MPR = #1/#2 MPR will be modeled as a linear regression with arm, genotype, and site as predictors.

Outcome measures

Measure	Genotype Results Plus Usual Care n=24 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at randomization	Usual Care Only n=20 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at the end of study
Medication Possession Ratio (MPR) From Baseline to Last Patient Follow-up	0.632 ratio Standard Deviation 0.333	0.685 ratio Standard Deviation 0.483

SECONDARY outcome

Timeframe: Baseline, Month 3, Month 8

Population: Only subjects reporting new prescriptions were included in the analysis.

The number of new prescriptions is binary and will be modeled with logistic regression with arm, genotype, and site as predictors. Any variables imbalanced between arms will also be included as covariates.

Outcome measures

Measure	Genotype Results Plus Usual Care n=74 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at randomization	Usual Care Only n=71 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at the end of study
Number of Participants Reporting New Statin Prescriptions Baseline to Month 3	41 Participants	27 Participants
Number of Participants Reporting New Statin Prescriptions Month 3 to Month 8	4 Participants	4 Participants

SECONDARY outcome

Timeframe: Month 3 and Month 8

Population: Only subjects that completed the Brief Pain Inventory surveys were included in the analysis.

Brief Pain Inventory data will be taken from 3 and 8-month follow up Patient Surveys. Pain severity and pain interference will be compared between groups. Both of these measures will be modeled as a linear regression with arm, genotype, and site as predictors. Transformations of the response may be explored depending on the distribution of the regression residuals. Baseline pain scores will also be included as a covariate to account for baseline variability.

Scores range from 0-10. Higher scores indicate higher pain severity.

Outcome measures

Measure	Genotype Results Plus Usual Care n=74 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at randomization	Usual Care Only n=67 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at the end of study
Brief Pain Inventory (BPI) Score - Pain Severity at Month 3 and Month 8 Month 3	1.608 units on a scale Standard Deviation 1.978	1.493 units on a scale Standard Deviation 1.854
Brief Pain Inventory (BPI) Score - Pain Severity at Month 3 and Month 8 Month 8	1.939 units on a scale Standard Deviation 1.93	1.689 units on a scale Standard Deviation 2.248

SECONDARY outcome

Timeframe: Month 3 and Month 8

Population: Only subjects that completed the Brief Pain Inventory surveys were included in the analysis.

Brief Pain Inventory data will be taken from 3 and 8-month follow up Patient Surveys. -Pain severity and pain interference will be compared between groups -Both of these measures will be modeled as a linear regression with arm as predictor. Baseline pain scores will also be included as a covariate to account for baseline variability.

Scores range from 0-10. Higher scores indicate higher pain interference with daily activities.

Outcome measures

Measure	Genotype Results Plus Usual Care n=74 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at randomization	Usual Care Only n=70 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at the end of study
Brief Pain Inventory (BPI) Score - Pain Interference at Month 3 and Month 8 Month 3	2.108 units on a scale Standard Deviation 1.141	1.971 units on a scale Standard Deviation 1.049
Brief Pain Inventory (BPI) Score - Pain Interference at Month 3 and Month 8 Month 8	1.964 units on a scale Standard Deviation 0.894	1.689 units on a scale Standard Deviation 0.941

SECONDARY outcome

Timeframe: Baseline, Month 3, Month 8

Population: Only subjects that completed the SF-12 Health Survey were included in the analysis.

Month 3 and Month 8 SF12 scores for mental and physical health will be compared. Both of these measures will be modeled as a linear regression with arm as predictor. Baseline SF-12 scores will also be included as a covariate to account for baseline variability.

Ranges from 0 to 100, where a zero score indicates the lowest level of physical health measured by the scales and 100 indicates the highest level of physical health

Outcome measures

Measure	Genotype Results Plus Usual Care n=82 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at randomization	Usual Care Only n=76 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at the end of study
Change in Short Form -12 Item (SF-12) Health Survey - Physical Component (PC) Baseline	42.244 units on a scale Standard Deviation 6.554	41.692 units on a scale Standard Deviation 7.281
Change in Short Form -12 Item (SF-12) Health Survey - Physical Component (PC) Month 3	41.389 units on a scale Standard Deviation 6.891	41.566 units on a scale Standard Deviation 5.708
Change in Short Form -12 Item (SF-12) Health Survey - Physical Component (PC) Month 8	42.179 units on a scale Standard Deviation 6.754	41.359 units on a scale Standard Deviation 5.721

SECONDARY outcome

Timeframe: Baseline, Month 3, Month 8

Population: Only subjects that completed the SF-12 Health Survey were included in the analysis.

Month 3 and Month 8 SF12 scores for mental and physical health will be compared. Both of these measures will be modeled as a linear regression with arm as predictor. Baseline SF-12 scores will also be included as a covariate to account for baseline variability.

Ranges from 0 to 100, where a zero score indicates the lowest level of mental health measured by the scales and 100 indicates the highest level of mental health.

Outcome measures

Measure	Genotype Results Plus Usual Care n=82 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at randomization	Usual Care Only n=76 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at the end of study
Change in Short Form -12 Item (SF-12) Health Survey - Mental Component (MC) Baseline	43.393 units on a scale 0 to 100 Standard Deviation 11.801	44.101 units on a scale 0 to 100 Standard Deviation 12.114
Change in Short Form -12 Item (SF-12) Health Survey - Mental Component (MC) Month 3	42.835 units on a scale 0 to 100 Standard Deviation 11.438	44.595 units on a scale 0 to 100 Standard Deviation 11.361
Change in Short Form -12 Item (SF-12) Health Survey - Mental Component (MC) Month 8	43.776 units on a scale 0 to 100 Standard Deviation 11.344	44.327 units on a scale 0 to 100 Standard Deviation 11.987

SECONDARY outcome

Timeframe: Baseline and Month 8

Population: Only subjects that completed the Physical Activity survey were included in the analysis

Activity levels will be compared at the end of 8-months. Activity levels are defined by a five-level ordinal variable (0-4; higher level corresponding to higher activity). which was calculated based on survey answers. An ordinal logistic regression model will be used with arm as predictor. The assumption of proportional odds will be checked, and if it is not met, a multinomial regression model will be used. -Baseline physical activity will also be included as a covariate to account for baseline variability.

Scale score (0-4): 0 - Inactivity, 1 - Ligh-intensity activity, 2 - moderate-intensity activity, 3 - Hard-intensity activity, 5 - very hard-intensity activity

Outcome measures

Measure	Genotype Results Plus Usual Care n=74 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at randomization	Usual Care Only n=72 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at the end of study
Physical Activity Scale Score Baseline	1.838 units on a scale Standard Deviation 1.629	1.736 units on a scale Standard Deviation 0.822
Physical Activity Scale Score Month 8	1.923 units on a scale Standard Deviation 1.152	1.667 units on a scale Standard Deviation 1.02

SECONDARY outcome

Timeframe: Baseline, Month 3, Month 8

Population: Only subjects that completed the Beliefs About Medications questionnaire were included in the analysis.

• Questionnaire administered at baseline, 3 months, and 8 months
• This instrument assesses beliefs regarding necessity and concerns related to disease-specific medications
• The score ranges from 5 to 25 representing the sum of 5 questions. This will be modeled with linear regression including treatment as predictor. Baseline BMQ scores will also be included as a covariate to account for baseline variability.

Higher score corresponds to higher thought necessity and higher thought concerns about taking the medication. The higher the necessity score, the more the patient believed statins necessary for their health. The higher the concerns score, the more the patient was concerned about taking stains (side effects).

Outcome measures

Measure	Genotype Results Plus Usual Care n=82 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at randomization	Usual Care Only n=75 Participants -Genetic testing for SLCO1B1\*5 allele reported to patient and provider at the end of study
Beliefs About Medications (BMQ) Score at Baseline, Month 3 and Month 8 Baseline, BMQ Necessity	13.878 units on a scale Standard Deviation 3.49	13.893 units on a scale Standard Deviation 3.443
Beliefs About Medications (BMQ) Score at Baseline, Month 3 and Month 8 Month 3, BMQ Necessity	14.347 units on a scale Standard Deviation 3.75	13.185 units on a scale Standard Deviation 3
Beliefs About Medications (BMQ) Score at Baseline, Month 3 and Month 8 Month 8, BMQ Necessity	14.148 units on a scale Standard Deviation 3.983	13.9 units on a scale Standard Deviation 3.487
Beliefs About Medications (BMQ) Score at Baseline, Month 3 and Month 8 Baseline, BMQ Concerns	15.962 units on a scale Standard Deviation 3.345	16.067 units on a scale Standard Deviation 2.974
Beliefs About Medications (BMQ) Score at Baseline, Month 3 and Month 8 Month 3, BMQ Concerns	14.471 units on a scale Standard Deviation 3.984	15.333 units on a scale Standard Deviation 3.914
Beliefs About Medications (BMQ) Score at Baseline, Month 3 and Month 8 Month 8, BMQ Concerns	13.585 units on a scale Standard Deviation 4.088	14.593 units on a scale Standard Deviation 3.71

Adverse Events

Genotype Results Plus Usual Care

Serious events: 4 serious events

Other events: 1 other events

Deaths: 1 deaths

Usual Care Only

Serious events: 6 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Genotype Results Plus Usual Care n=83 participants at risk * Genetic testing for SLCO1B1\*5 allele * Reporting for SLCO1B1\*5 allele at randomization Reporting for SLCO1B1\*5 allele at randomization: Reporting of genetic test results to patient and provider at randomization Genetic testing for SLCO1B1\*5 allele: Blood test for SLCO1B1\*5 allele	Usual Care Only n=76 participants at risk * Genetic testing for SLCO1B1\*5 allele * Reporting for SLCO1B1\*5 allele at the end of study Reporting for SLCO1B1\*5 allele at the end: Usual care recommendations provided to patient and provider at randomization. Genotyping results provided at the end of study. Genetic testing for SLCO1B1\*5 allele: Blood test for SLCO1B1\*5 allele
Hepatobiliary disorders Liver function testing abnormality	0.00% 0/83 • Baseline through Month 8	1.3% 1/76 • Number of events 1 • Baseline through Month 8
Cardiac disorders Chest Pain	0.00% 0/83 • Baseline through Month 8	2.6% 2/76 • Number of events 2 • Baseline through Month 8
Blood and lymphatic system disorders Hospitalization for bleeding	0.00% 0/83 • Baseline through Month 8	1.3% 1/76 • Number of events 1 • Baseline through Month 8
Respiratory, thoracic and mediastinal disorders Respiratory Distress	0.00% 0/83 • Baseline through Month 8	1.3% 1/76 • Number of events 1 • Baseline through Month 8
Gastrointestinal disorders Nausea, vomiting, abdominal pain	1.2% 1/83 • Number of events 1 • Baseline through Month 8	0.00% 0/76 • Baseline through Month 8
Infections and infestations Suspected MRSA bacteremia	1.2% 1/83 • Number of events 1 • Baseline through Month 8	0.00% 0/76 • Baseline through Month 8
Cardiac disorders Atrial fibrillation	1.2% 1/83 • Number of events 1 • Baseline through Month 8	0.00% 0/76 • Baseline through Month 8
Cardiac disorders Myocardial infarction	0.00% 0/83 • Baseline through Month 8	1.3% 1/76 • Number of events 1 • Baseline through Month 8
Renal and urinary disorders Renal Failure	1.2% 1/83 • Number of events 1 • Baseline through Month 8	0.00% 0/76 • Baseline through Month 8

Other adverse events

Measure	Genotype Results Plus Usual Care n=83 participants at risk * Genetic testing for SLCO1B1\*5 allele * Reporting for SLCO1B1\*5 allele at randomization Reporting for SLCO1B1\*5 allele at randomization: Reporting of genetic test results to patient and provider at randomization Genetic testing for SLCO1B1\*5 allele: Blood test for SLCO1B1\*5 allele	Usual Care Only n=76 participants at risk * Genetic testing for SLCO1B1\*5 allele * Reporting for SLCO1B1\*5 allele at the end of study Reporting for SLCO1B1\*5 allele at the end: Usual care recommendations provided to patient and provider at randomization. Genotyping results provided at the end of study. Genetic testing for SLCO1B1\*5 allele: Blood test for SLCO1B1\*5 allele
Vascular disorders Stroke	1.2% 1/83 • Number of events 1 • Baseline through Month 8	0.00% 0/76 • Baseline through Month 8

Additional Information

Dr. Deepak Voora

Duke University

Phone: 919-668-1755

Email: Deepak.vorra@duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place