Hyperlipidemia, Hypertension
Conditions
Keywords
combination pill, polypill, primary prevention
Brief summary
In this study the investigators will examine the effect of the polypill on medication adherence, systolic blood pressure, and LDL cholesterol over a 12 month span.
Detailed description
The purpose of this study is to assess if a polypill-based approach to primary CVD prevention is feasible in a low socioeconomic status population. The study will assess whether a polypill approach is associated with better cardiovascular risk factor control compared with usual care. The polypill will be supplied as a compounded pill containing atorvastatin 10 mg, amlodipine 2.5 mg, losartan 25 mg, and hydrochlorothiazide 12.5 mg. The medications in the polypill have been extensively evaluated individually and in combination. Each of the medications in the polypill is approved by the United States Food and Drug Administration (FDA) and widely administered in the US for the treatment of and prevention of cardiovascular disease. The doses of each component medication included in the polypill are low, which should minimize the chance of any potential side-effects. In this study we assess medication adherence, systolic blood pressure, and LDL cholesterol over a 12 month span, in subjects taking the polypill versus subjects under usual care.
Interventions
DRUGPolypill (atorvastatin, amlodipine, losartan, and hydrochlorothiazide)
Sponsors
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Enrolled at the SCCS site in Mobile, Alabama, obtain care at Franklin Primary Health Center, or live in the surrounding area. * Aged 45-75 years * Baseline systolic blood pressure ≥120 mm Hg. In this open-label trial, the study physicians are permitted to prescribe any additional medication deemed appropriate to achieve blood pressure control.
Exclusion criteria
* History of coronary heart disease or stroke * History of cancer, except for basal cell skin cancer * History of liver disease, not including chronic, clinically-stable hepatitis * Laboratory evidence of hepatic dysfunction (an alanine aminotransferase level more than two times the upper limit of the normal range) * Known renal disease, estimated creatinine clearance \< 60 * Current use of more than 2 anti-hypertensive medications * LDL cholesterol ≥190 mg/dl * Insulin-dependent diabetes * Known intolerance to any of the components of the polypill * Potassium \<3.4 or \>5.5 mEq/L * Use of medications that interact with statins, including those affecting the cytochrome P450 system * Current use of diuretics for indications other than hypertension * Comorbidities that might be expected to limit lifespan during the 12-month follow-up period * Inability to provide consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Systolic Blood Pressure | 12 months | polypill versus usual care |
| Medication Adherence-Percentage of Pills Taken | 12 months | polypill arm-evaluation via pill counts. |
| LDL Cholesterol | 12 months | Polypill versus usual care |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LDL Cholesterol | 2 months | polypill versus usual care |
| Systolic Blood Pressure | 2 months | polypill versus usual care |
| Inflammatory Profile | Baseline and 12 months | Plasma levels of IL-17, IFN-g, IL-6, IL-10, high sensitivity C-reactive protein, TNFa, IL-4. |
| Insulin Resistance | Baseline and 12 months | Measurement of HOMA-IR using fasting glucose and insulin. |
| Medication Adherence | 2 months | polypill-percentage of pills taken, evaluated via pill counts |
| Drug Metabolite Profile | 12 months | LC/MS/MS-based drug metabolite profile assay screen in the polypill arm. |
Countries
United States
Participant flow
Pre-assignment details
Potentially eligible participants were invited to complete a baseline visit. During baseline visit, if eligibility confirmed, patients then randomized in open-label 1:1 fashion to either polypill arm or usual care arm. Only if baseline visit labs yielded an exclusionary result were participants then disqualified from further study participation.
Participants by arm
| Arm | Count |
|---|---|
| Usual Care Subjects in this arm will not receive any investigational medications. They will continue to receive usual medical care, as directed by their primary care providers. | 155 |
| Polypill The study medication will be a fixed-dose combination pill (polypill) containing: Atorvastatin 10 mg, amlodipine 2.5 mg, losartan 25 mg, and hydrochlorothiazide 12.5 mg.
Polypill will be taken once daily.
Polypill (atorvastatin, amlodipine, losartan, and hydrochlorothiazide) | 148 |
| Total | 303 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 2 |
| Overall Study | Lost to Follow-up | 6 | 15 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Usual Care | Polypill | Total |
|---|---|---|---|
| Age, Continuous | 56 years STANDARD_DEVIATION 6 | 56 years STANDARD_DEVIATION 6 | 56 years STANDARD_DEVIATION 6 |
| LDL Cholesterol | 112 mg/dL STANDARD_DEVIATION 37 | 114 mg/dL STANDARD_DEVIATION 32 | 113 mg/dL STANDARD_DEVIATION 34 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 151 Participants | 141 Participants | 292 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 7 Participants | 11 Participants |
| Region of Enrollment United States | 155 participants | 148 participants | 303 participants |
| Sex: Female, Male Female | 99 Participants | 65 Participants | 164 Participants |
| Sex: Female, Male Male | 56 Participants | 83 Participants | 139 Participants |
| Systolic Blood Pressure | 140 mm Hg STANDARD_DEVIATION 17 | 140 mm Hg STANDARD_DEVIATION 18 | 140 mm Hg STANDARD_DEVIATION 17 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 155 | 2 / 148 |
| other Total, other adverse events | 0 / 155 | 0 / 148 |
| serious Total, serious adverse events | 3 / 155 | 2 / 148 |
Outcome results
Primary
LDL Cholesterol
Polypill versus usual care
Time frame: 12 months
Population: \# of participants in polypill arm analyzed (126) does not match number of polypill participants completed (128; in the participant flow overview) because we were unable to obtain LDL values at baseline for 2 Polypill participants. The lab was unable to calculate and a reflex direct LDL was not processed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | LDL Cholesterol | 109 mg/dL | Standard Deviation 32 |
| Polypill | LDL Cholesterol | 98 mg/dL | Standard Deviation 35 |
Primary
Medication Adherence-Percentage of Pills Taken
polypill arm-evaluation via pill counts.
Time frame: 12 months
Population: adherence not assessed in usual care arm; incomplete data for 27 polypill participants, resulting in 101 analyzed of 128 polypill participants who completed 12 month visits
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polypill | Medication Adherence-Percentage of Pills Taken | 86 percentage of pills taken |
Primary
Systolic Blood Pressure
polypill versus usual care
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Systolic Blood Pressure | 138 mm Hg | Standard Deviation 23 |
| Polypill | Systolic Blood Pressure | 131 mm Hg | Standard Deviation 21 |
Secondary
Drug Metabolite Profile
LC/MS/MS-based drug metabolite profile assay screen in the polypill arm.
Time frame: 12 months
Population: Funding is no longer available to complete the analysis of biomarker measurements. In addition, no future funding is anticipated in order to complete this analysis.
Secondary
Inflammatory Profile
Plasma levels of IL-17, IFN-g, IL-6, IL-10, high sensitivity C-reactive protein, TNFa, IL-4.
Time frame: Baseline and 12 months
Population: Funding is no longer available to complete the analysis of biomarker measurements. In addition, no future funding is anticipated in order to complete this analysis.
Secondary
Insulin Resistance
Measurement of HOMA-IR using fasting glucose and insulin.
Time frame: Baseline and 12 months
Population: Funding is no longer available to complete the analysis of biomarker measurements. In addition, no future funding is anticipated in order to complete this analysis.
Secondary
LDL Cholesterol
polypill versus usual care
Time frame: 2 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | LDL Cholesterol | 108 mg/dL | Standard Deviation 35 |
| Polypill | LDL Cholesterol | 90 mg/dL | Standard Deviation 33 |
Secondary
Medication Adherence
polypill-percentage of pills taken, evaluated via pill counts
Time frame: 2 months
Population: adherence not assessed in usual care arm; incomplete data for 32 polypill participants, resulting in 106 analyzed of 138 polypill participants who completed 2 month visits
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polypill | Medication Adherence | 98 percentage of pills taken |
Secondary
Systolic Blood Pressure
polypill versus usual care
Time frame: 2 months
Population: The numbers of participants analyzed do not match those of the completed (in the participant flow overview) because this assessment was completed at baseline and 2 months; 291 patients (153 usual care, 138 Polypill) completed 2-month follow-up, whereas 275 (147 Usual Care, 128 Polypill) completed 12-month follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Systolic Blood Pressure | 133 mm Hg | Standard Deviation 19 |
| Polypill | Systolic Blood Pressure | 128 mm Hg | Standard Deviation 19 |