Cluster Randomized Trial of a Digital Quality Improvement Intervention on LDLCholesterol Control

Study Overview
=================
Brief Summary
-----------------
Elevation in low density lipoprotein (LDL) cholesterol (LDL-C) is a causal risk factor for atherosclerotic established cardiovascular disease (ASCVD). Reduction of LDL-C with statins has been clearly demonstrated as a robust and cost-effective way of reducing the burden of ASCVD in individuals at risk. ASCVD is the leading cause of death and disability in Brazil and therefore prevention guidelines recommend LDL-C reduction with the aim of reducing disease burden in individuals at risk. Studies have shown a clear hiatus on awareness and treatment of cholesterol in Brazil. Thus, it became imperative to develop knowledge translation projects aiming at bridging the gap between science and clinical practice and ultimately leading to better outcomes. Cluster randomized clinical trials are the highest quality type of clinical research to test educational and active interventions aimed at changing behaviors or clinical practices. Therefore, this study is a pragmatic cluster randomized trial to assess the effect of a digitally enabled quality improvement intervention on LDL-C control in atherosclerotic established cardiovascular disease (ASCVD) patients.

Detailed Description
-----------------
Elevation in low density lipoprotein (LDL) cholesterol (LDL-C) is a causal risk factor for atherosclerotic established cardiovascular disease (ASCVD). Reduction of LDL-C with statins has been clearly demonstrated as a robust and cost-effective way of reducing the burden of ASCVD in individuals at risk. ASCVD is the leading cause of death and disability in Brazil and therefore prevention guidelines recommend LDL-C reduction with the aim of reducing disease burden in individuals at risk. Studies have shown a clear hiatus on awareness and treatment of cholesterol in Brazil. Thus, it became imperative to develop knowledge translation projects aiming at bridging the gap between science and clinical practice and ultimately leading to better outcomes. Cluster randomized clinical trials are the highest quality type of clinical research to test educational and active interventions aimed at changing behaviors or clinical practices.To our knowledge, data from this study will be crucial to leverage LDL-C treatment in Brazil, considering efforts to improve population health. The present study represents one of the first trials testing a quality improvement (QI) intervention targeted to LDL-C reduction in ASCVD patients conducted in a middle-income country. These results will address whether the proposed QI intervention is feasible and effective in these settings. Therefore, this study is a pragmatic cluster randomized trial to assess the effect of a digitally enabled QI intervention on LDL-C control in ASCVD patients. This study will have 2 phases. Phase 1 will be an observational phase prior to randomization of clusters with the objective to assess the baseline LDL-C levels achieved for target patients. Phase 2 will be an interventional phase, in which clusters will be randomized to the digitally enabled quality improvement intervention or usual care, with the objective to assess the effect of a digitally enabled QI intervention on control of LDL-C levels in ASCVD patients.

Official Title
-----------------
A Pragmatic Cluster Randomized Trial to Assess the Effect of a Digitally Enabled Quality Improvement Intervention on LDL Cholesterol Control in Atherosclerotic Established Cardiovascular Disease Patients

Conditions
-----------------
Cardiovascular Diseases, Atherosclerosis, Dyslipidemias

Intervention / Treatment
-----------------
* Behavioral: Digitally-enabled Multifaceted Quality Improvement Intervention
* Behavioral: Usual care


Participation Criteria
=================
Eligibility Criteria
-----------------
Patient Eligibility Criteria: Inclusion Criteria: Capable of using a smartphone with iOS or Android System AND Established ASCVD, including: Coronary Artery Disease (CAD): Prior myocardial infarction Prior coronary revascularization - percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) Angiographic or computerized tomography (CT)-imaging evidence of coronary atherosclerosis (≥ 50% stenosis in at least one major epicardial coronary artery) Stroke: • Prior ischemic stroke thought not to be caused by an embolic cause (e.g., atrial fibrillation, valvular heart disease or mural thrombus) Peripheral Artery Disease (PAD): Prior documentation of a resting ankle-brachial index ≤ 0.9 History of prior percutaneous or surgical revascularization of an iliac, femoral, or popliteal artery Prior non-traumatic amputation of a lower extremity due to peripheral artery disease History of prior percutaneous or surgical carotid artery revascularization Carotid Stenosis > 50% on prior angiography or ultrasound AND Provision of informed consent Exclusion Criteria: Patients with a recent cardiovascular event, less than 3 months prior to study inclusion Patients with LDL-C ≤ 70 mg/dL Current participation in other clinical trials involving lipid lowering treatments Patients that do not consent to trial participation Cluster Eligibility Criteria: Inclusion Criteria: Outpatient Clinics from public or private hospitals OR, Private Practices, which assist patients with previous ASCVD on secondary prevention that provide a unit/institution authorization form for participation in the trial AND Minimum monthly volume of 20 ASCVD patients Exclusion Criteria: Clusters that do not provide the unit/institution authorization form.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Cluster randomized clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>Real-world evidence (RWE) platform to provide data on their clinical practice + usual care + Digitally-enabled Multifaceted Quality Improvement Intervention | Behavioral: Digitally-enabled Multifaceted Quality Improvement Intervention<br>* Digitally-enabled multifaceted strategy in addition to access to a RWE platform to provide clinical data. The digitally-enabled multifaceted strategy will include various tools that will provide support to the health professionals responsible for treating ASCVD patients in each center as well as patients, including: Knowledge of effective lipid lowering therapies Clinical decision support Audit and feedback on adherence to optimal clinical management Audit and feedback on LDL-C control<br>|
| Active Comparator: Control group<br>RWE platform to provide data on their clinical practice + usual care | Behavioral: Usual care<br>* Health professionals responsible for treating ASCVD patients in each center will continue to provide usual care to ASCVD patients in addition to provide data through a RWE platform.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: LDL-C levels | LDL-C levels measured at a single visit | Baseline | 
| Phase 2: LDL-C | LDL-C levels measured at the end of follow up of Phase 2 | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Prescribed lipid-lowering therapy | Percentage of patients on prescribed lipid-lowering therapy | Baseline | 
| Phase 1: Prescribed combination lipid-lowering therapy | Percentage of patients on prescribed combination lipid-lowering therapy | Baseline | 
| Phase 1: Prescribed intensive lipid-lowering therapy | Percentage of patients on prescribed intensive lipid-lowering therapy | Baseline | 
| Phase 1: Prescription of high intensity statins | Percentage of prescription of high intensity statins | Baseline | 
| Phase 1: Prescription of ezetimibe | Percentage of prescription of ezetimibe | Baseline | 
| Phase 1: Prescription of PCSK9 inhibitors | Percentage of prescription of PCSK9 inhibitors | Baseline | 
| Phase 1: LDL-C < 50 mg/dL | Percentage of patients with LDL-C < 50 mg/dL | Baseline | 
| Phase 2: Prescribed lipid-lowering therapy | Percentage of patients on prescribed lipid-lowering therapy | 12 months | 
| Phase 2: Prescribed combination lipid-lowering therapy | Percentage of patients on prescribed combination lipid-lowering therapy | 12 months | 
| Phase 2: Prescribed intensive lipid-lowering therapy | Percentage of patients on prescribed intensive lipid-lowering therapy | 12 months | 
| Phase 2: Prescription of high intensity statins | Percentage of prescription of high intensity statins | 12 months | 
| Phase 2: Prescription of moderate intensity statins | Percentage of prescription of moderate intensity statins | 12 months | 
| Phase 2: Prescription of low intensity statins | Percentage of prescription of low intensity statins | 12 months | 
| Phase 2: Prescription of ezetimibe | Percentage of prescription of ezetimibe | 12 months | 
| Phase 2: Prescription of PCSK9 inhibitors | Percentage of prescription of PCSK9 inhibitors | 12 months | 
| Phase 2: LDL-C < 50 mg/dL | Percentage of patients with LDL-C < 50 mg/dL | 12 months | 
| Phase 2: LDL-C relative change | Change in LDL-C relative to baseline | 12 months | 
| Phase 2: LDL-C reduction of ≥50% | Percentage of patients with LDL-C reduction of ≥50% relative to baseline | 12 months | 
| Phase 2: Barriers for drug prescription | Barriers for drug prescription at the system (cluster) and physician level | 12 months | 
| Phase 2: Adherence to prescribed lipid-lowering therapy | Patient´s adherence to prescribed lipid-lowering therapy | 12 months | 
| Phase 2: Barriers for drug adherence | Patient´s barriers for drug adherence | 12 months | 
| Phase 2: Intolerance to Statins | Percentage of patients with intolerance to Statins | 12 months | 
| Phase 2: 5P-MACE (Major Cardiovascular Events) | Composite endpoint of time to first occurrence of a major cardiovascular event 5P-MACE including cardiovascular deaths. non-fatal stroke or transient ischemic attack (TIA), non-fatal myocardial infarction, hospitalization for unstable angina, or coronary revascularization, whichever occurs first | 12 months | 
| Phase 2: 3P-MACE (Major Cardiovascular Events) | Composite endpoint of time to first occurrence of a major cardiovascular event 3P-MACE including cardiovascular deaths, non-fatal stroke or TIA, or non-fatal myocardial infarction, whichever occurs first | 12 months | 
| Phase 2: Cardiovascular death | Time to cardiovascular death | 12 months | 
| Phase 2: Death from any cause | Time to death from any cause | 12 months | 
| Phase 2: Myocardial infarction | Time to first myocardial infarction | 12 months | 
| Phase 2: Stroke | Time to first stroke | 12 months | 
| Phase 2: Coronary revascularization | Time to first coronary revascularization | 12 months | 
| Phase 2: Total deaths | Total deaths within 12 months from inclusion | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cardiovascular diseases, Atherosclerosis, Dyslipidemias