Study identifier:D5130R00030
ClinicalTrials.gov identifier:NCT02406677
EudraCT identifier:N/A
CTIS identifier:N/A
Affordability and Real-world Antiplatelet Treatment Effectiveness After Myocardial Infarction Study
Cost Sharing, Acute Coronary Syndrome
Phase 4
No
-
All
11001
Interventional
18 Years - 130 Years
Allocation: Randomized
Endpoint Classification: Efficacy
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Health Services Research
Verified 01 Sept 2019 by AstraZeneca
AstraZeneca
Duke Clinical Research Institute
Current patterns of P2Y12 receptor inhibitor use provide an excellent opportunity to test the impact of copayment reduction on clinician choice of medication, patient adherence, and clinical outcomes. The ARTEMIS trial is a practical multicenter, cluster randomized clinical trial that will assess the impact of copayment reduction by equalizing the copayment of clopidogrel and ticagrelor. ARTEMIS will assess prescribing patterns, patient medication adherence, and clinical outcomes up to one year. We hypothesize that reducing outÂ-of-Âpocket cost for P2Y12 receptor inhibitor will lead to improved adherence. Additionally, copayment reduction of both generic and brand antiplatelet agents may lead to a reduction in MACE risk. This is in part due to greater adherence to an evidence-Âbased secondary prevention medication. Additionally the reduction in MACE may reflect greater selection of a more potent antiplatelet agent that has been shown to reduce MACE in randomized clinical trials, as provider choice of antiplatelet therapy will be primarily driven by risk benefit assessment rather than the cost burden to the patient.
ARTEMIS is a prospective, cluster-randomized clinical trial that will evaluate whether patient copayment elimination significantly influences antiplatelet therapy selection and long-term adherence, as well as patient outcomes and overall cost of care after acute myocardial infarction. Approximately 11,000 patients with ST-elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) will be enrolled at the approximately 300 hospitals in this study. Study sites selected for ARTEMIS will be geographically diverse, and will represent a diversity of hospital types and capabilities (e.g., teaching hospital, community hospital, etc). After institutional review board (IRB) approval of the study, each hospital will be randomized into either the intervention arm or the control arm. Hospitals randomized to the intervention arm will have the opportunity to offer enrolled patients either clopidogrel (generic P2Y12 receptor inhibitor option) or ticagrelor (brand P2Y12 receptor inhibitor option) without patient contribution to copayment in the next 12 months after the index MI discharge. Hospitals in the control arm will provide care per usual clinical routine. Notably, for both intervention and control arms, all patient management decisions (including the choice of antiplatelet therapy) are completely at the discretion of the care providers. Duration of antiplatelet therapy will also be at the discretion of care providers. All enrolled patients will be followed up to 15 months after index MI discharge to collect data on longitudinal treatment patterns and outcomes. Primary and secondary endpoints will be assessed at 12 months. An additional three months of follow up will assess for antiplatelet persistence and clinical events after discontinuation of the copayment intervention. Centralized follow-up will be conducted every 3 months via telephone or web-based contact.
Location
Location
Mount Clemens, MI, United States, 48043
Location
Bridgewater, NJ, United States, 08807
Location
Huntsville, AL, United States, 35613
Location
Hudson, FL, United States, 34667
Location
Doylestown, PA, United States, 18901
Location
Southfield, MI, United States, 48075
Location
Raleigh, NC, United States, 27607
Location
Minneapolis, MN, United States, 55407
Arms | Assigned Interventions |
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Experimental: Copayment Intervention Arm Sites in the intervention arm will provide patients with a study voucher card to offset any patient copayments or medication card for the filling of any prescriptions of clopidogrel or ticagrelor. | Other: Study voucher card Study voucher card to offset any patient copayments or medication costs for the filling of any prescriptions of clopidogrel or ticagrelor |
No Intervention: Usual Care Arm For hospitals randomized to the control arm, all patients receive usual care and no study intervention is performed. | - |
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations |
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Study recruited patients on P2Y12 inhibitor therapy with US-based health insurance. Recruitment into 301 study sites (hospitals) in the US was conducted from June, 2015 to September, 2016. The study evaluated whether patient copayment reduction significantly influenced antiplatelet therapy selection and long-term adherence. |
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment |
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The study population included patients STEMI or NSTEMI who were treated with a P2Y12 receptor inhibitor. After patient enrollment into hospitals, each hospital was randomized into either the intervention or the control arm (cluster randomization). The randomization scheme was changed from 1:1 to 2:1 mid-study. 12 month study duration. |
Description | |
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Copayment Intervention Arm | Sites in the intervention arm will provide patients with a study voucher card to offset any patient copayments or medication card for the filling of any prescriptions of clopidogrel or ticagrelor. |
Usual Care Arm | For hospitals randomized to the control arm, all patients receive usual care and no study intervention is performed. |
Copayment Intervention Arm | Usual Care Arm | |
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STARTED | 6436 | 4565 |
COMPLETED | 6135 | 3967 |
NOT COMPLETED | 301 | 598 |
Death | 16 | 8 |
Discharged without P2Y12 | 1 | 3 |
Discharged on prasugrel | 283 | 587 |
Withdrawal by Subject | 1 | 0 |
Description | |
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Copayment Intervention Arm | Sites in the intervention arm will provide patients with a study voucher card to offset any patient copayments or medication card for the filling of any prescriptions of clopidogrel or ticagrelor. |
Usual Care Arm | For hospitals randomized to the control arm, all patients receive usual care and no study intervention is performed. |
Copayment Intervention Arm | Usual Care Arm | Total | |
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Number of Participants
[units: Participants] |
6135 | 3967 | 10102 |
Age Continuous [units: Years] Mean ± Standard Deviation Age
|
62.08 ± 11.78 | 62.10 ± 11.55 | 62.09 ± 11.69 |
Sex: Female, Male
[1] [units: Participants] |
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Female | 1942 | 1285 | 3227 |
Male | 4193 | 2682 | 6875 |
Ethnicity (NIH/OMB)
[2] [units: Participants] |
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Hispanic or Latino | 188 | 222 | 410 |
Not Hispanic or Latino | 5947 | 3745 | 9692 |
Unknown or Not Reported | 0 | 0 | 0 |
Insurance Payors - Private Health Insurance
[3] [units: Participants] |
3864 | 2540 | 6404 |
Race/Ethnicity, Customized
[4] [units: Participants] Race
|
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White | 5495 | 3416 | 8911 |
Non-White | 640 | 551 | 1191 |
Measure Type | Primary |
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Measure Name | Kaplan-Meier Cumulative Incidence Rate of Major Adverse Cardiovascular Events |
Measure Description | To determine if patient copayment reduction leads to lower risk of MACE (composite of death, MI, and stroke) at 1 year after discharge. |
Time Frame | 12 months |
Safety Issue? | No |
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
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Primary Population |
Description | |
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Copayment Intervention Arm | Sites in the intervention arm will provide patients with a study voucher card to offset any patient copayments or medication card for the filling of any prescriptions of clopidogrel or ticagrelor. |
Usual Care Arm | For hospitals randomized to the control arm, all patients receive usual care and no study intervention is performed. |
Copayment Intervention Arm | Usual Care Arm | |
---|---|---|
Number of
Participants Analyzed [units:participants] |
6135 | 3967 |
Kaplan-Meier Cumulative Incidence Rate of Major Adverse Cardiovascular Events [units: Percentage of Participants] Number (95% Confidence Interval) |
10.17 (9.4 to 10.93) | 10.93 (9.67 to 11.60) |
Groups [1] | All groups |
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Method [3] | Regression, Cox |
P-Value [4] | 0.3503 |
Hazard Ratio (HR) [5] | 1.073 |
95% Confidence Interval | ( 0.925 to 1.246 ) |
[1] | Additional details about the analysis, such as null hypothesis and power calculation: |
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No text entered. | |
[3] | Other relevant information, such as adjustments or degrees of freedom: |
Cox proportional hazards model accounting for within hospital clustering using robust standard errors | |
[4] | Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance: |
No text entered. | |
[5] | Other relevant estimation information: |
Usual Care arm is the reference group |
Measure Type | Primary |
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Measure Name | Percentage of Patients with Long Term Non-persistence to P2Y12 receptor inhibitor |
Measure Description | To determine if patient copayment reduction leads to higher long-term persistence of any P2Y12 receptor inhibitor at 1 year after discharge. |
Time Frame | 12 months |
Safety Issue? | No |
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
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Primary Population |
Description | |
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Copayment Intervention Arm | Sites in the intervention arm will provide patients with a study voucher card to offset any patient copayments or medication card for the filling of any prescriptions of clopidogrel or ticagrelor. |
Usual Care Arm | For hospitals randomized to the control arm, all patients receive usual care and no study intervention is performed. |
Copayment Intervention Arm | Usual Care Arm | |
---|---|---|
Number of
Participants Analyzed [units:participants] |
6135 | 3967 |
Percentage of Patients with Long Term Non-persistence to P2Y12 receptor inhibitor [units: Percentage of Patients] |
12.96 | 16.21 |
Groups [1] | All groups |
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Method [3] | Regression, Logistic |
P-Value [4] | 0.0260 |
Odds Ratio (OR) [5] | 0.838 |
95% Confidence Interval | ( 0.717 to 0.979 ) |
[1] | Additional details about the analysis, such as null hypothesis and power calculation: |
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No text entered. | |
[3] | Other relevant information, such as adjustments or degrees of freedom: |
Logistic regression model with parameters estimated using GEE to account for within hospital clustering for selected patient characteristics | |
[4] | Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance: |
No text entered. | |
[5] | Other relevant estimation information: |
No text entered. |
Measure Type | Secondary |
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Measure Name | P2Y12 receptor inhibitor selection |
Measure Description | To evaluate whether reducing patient copayments for both generic and brand P2Y12 receptor inhibitor options affects medication selection at discharge. |
Time Frame | 12 months |
Safety Issue? | No |
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
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Primary Population |
Description | |
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Copayment Intervention Arm - Clopidogrel | Patients in the intervention arm discharged on Clopidogrel |
Copayment Intervention Arm - Ticagrelor | Patients in the intervention arm discharged on Ticagrelor |
Usual Care Arm - Clopidogrel | Patients in the Usual Care Arm discharged on Clopidogrel |
Usual Care Arm - Ticagrelor | Patients in the Usual Care Arm discharged on Ticagrelor |
Copayment Intervention Arm - Clopidogrel | Copayment Intervention Arm - Ticagrelor | Usual Care Arm - Clopidogrel | Usual Care Arm - Ticagrelor | |
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Number of
Participants Analyzed [units:participants] |
6135 | 6135 | 3967 | 3967 |
P2Y12 receptor inhibitor selection [units: Percentage of Patients] |
36.0 | 59.6 | 54.7 | 32.4 |
Groups [1] | All groups |
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Method [3] | Regression, Logistic |
P-Value [4] | <0.0001 |
Odds Ratio (OR) [5] | 2.035 |
95% Confidence Interval | ( 1.564 to 2.649 ) |
[1] | Additional details about the analysis, such as null hypothesis and power calculation: |
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No text entered. | |
[3] | Other relevant information, such as adjustments or degrees of freedom: |
Logistic regression with GEE to account for within hospital clustering | |
[4] | Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance: |
No text entered. | |
[5] | Other relevant estimation information: |
No text entered. |
Time Frame | Safety data was not actively collected in the ARTEMIS trial for the following reasons: • The safety profile of Brilinta (ticagrelor) is well established • ARTEMIS is a non-indication seeking interventional study that did not include a safety objective; the intervention involved co-payment only. Only Deaths were collected over the course of the 15-month study period. |
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Additional Description | Adverse Events were only assessed with respect to All-Cause Mortality. |
Description | |
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Copayment Intervention Arm | Sites in the intervention arm will provide patients with a study voucher card to offset any patient copayments or medication card for the filling of any prescriptions of clopidogrel or ticagrelor. |
Usual Care Arm | For hospitals randomized to the control arm, all patients receive usual care and no study intervention is performed. |
Copayment Intervention Arm | Usual Care Arm | |
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Total, serious adverse events | ||
# participants affected / at risk | 0/0 | 0/0 |
Time Frame | Safety data was not actively collected in the ARTEMIS trial for the following reasons: • The safety profile of Brilinta (ticagrelor) is well established • ARTEMIS is a non-indication seeking interventional study that did not include a safety objective; the intervention involved co-payment only. Only Deaths were collected over the course of the 15-month study period. |
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Additional Description | Adverse Events were only assessed with respect to All-Cause Mortality. |
Threshold above which other adverse events are reported | 0% |
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Description | |
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Copayment Intervention Arm | Sites in the intervention arm will provide patients with a study voucher card to offset any patient copayments or medication card for the filling of any prescriptions of clopidogrel or ticagrelor. |
Usual Care Arm | For hospitals randomized to the control arm, all patients receive usual care and no study intervention is performed. |
Copayment Intervention Arm | Usual Care Arm | |
---|---|---|
Total, other (not including serious) adverse events | ||
# participants affected / at risk | 0/0 | 0/0 |
Principal Investigators are NOT employed by the organization sponsoring the study. | ||||||
There IS 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. | ||||||
The agreement is:
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data |
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1. Imbalances in enrollment and patient characteristics were expected in this cluster-randomized design due to differential incentives to enroll. 2. The cluster-randomized design renders the usual care arm vulnerable to potential bias to the null. |
Name/Title: | Naeem Khan, MD, VP, CVMD TA |
Organization: | AstraZeneca Pharmaceuticals LP |
Phone | 302-886-5526 |
E-mail: | [email protected] |
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