Cluster Randomized Trial of a Digital Quality Improvement Intervention on LDLCholesterol Control (SAPPHIRE-LDL)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Atherosclerosis; Dyslipidemias
• Intervention / Treatment: Behavioral: Digitally-enabled Multifaceted Quality Improvement Intervention; Behavioral: Usual care

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.

• Study Type: Interventional
• Enrollment (Estimated): 2800
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Karla E Santo, PhD; Phone Number: +55 11 2151-5915; Email: karla.santo@einstein.br

Study Locations

• Brazil
  • BA
    • Salvador, BA, Brazil
      • Recruiting
      • Hospital da Bahia
      • Contact: Marianna Dracoulakis
      • Principal Investigator: Marianna Dracoulakis, MD
  • MG
    • Poços De Caldas, MG, Brazil
      • Recruiting
      • Hospital Santa Lúcia
      • Contact: Frederico Dall'Orto
      • Principal Investigator: Frederico Dall'Orto, MD
  • PR
    • Campina Grande Do Sul, PR, Brazil
      • Recruiting
      • Hospital e Maternidade Angelina Caron
      • Contact: Dalton Precoma
      • Principal Investigator: Dalton Precoma, MD
  • SC
    • Joinville, SC, Brazil
      • Recruiting
      • Hospital Regional Hans Dieter Schmidt
      • Contact: Conrado HOFFMANN FILHO
      • Principal Investigator: Conrado HOFFMANN FILHO, MD
  • SE
    • Aracaju, SE, Brazil
      • Recruiting
      • Centro de Pesquisa Clínica do Coração
      • Contact: Fabio Silveira
      • Principal Investigator: Fabio Silveira, MD
  • SP
    • Bragança Paulista, SP, Brazil
      • Recruiting
      • Hospital Universitário São Francisco de Assis
      • Contact: Murillo Antunes
      • Principal Investigator: Murillo Antunes, MD
    • Campinas, SP, Brazil
      • Recruiting
      • Instituto de Pesquisa Clínica de Campinas
      • Contact: Jose Francisco Saraiva
      • Principal Investigator: Jose Francisco Saraiva, MD
    • Marília, SP, Brazil
      • Recruiting
      • Irmandade da Santa Casa de Misericórdia de Marilia
      • Contact: Pedro Andrade
      • Principal Investigator: Pedro Andrade, MD
    • Matão, SP, Brazil
      • Recruiting
      • Hospital Carlos Fernando Malzoni
      • Principal Investigator: Cesar Minelli, MD
      • Contact: Cesar Minelli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Patient Eligibility Criteria:

Inclusion Criteria:

• Capable of using a smartphone with iOS or Android System AND

• Established ASCVD, including:

  1. 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)

  2. Stroke:

     • Prior ischemic stroke thought not to be caused by an embolic cause (e.g., atrial fibrillation, valvular heart disease or mural thrombus)

  3. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; 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; 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
Active Comparator: Control group; RWE platform to provide data on their clinical practice + usual care	Behavioral: Usual care; 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.

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

Collaborators and Investigators

• Sponsor: Hospital Israelita Albert Einstein
• Collaborators: Novartis; epHealth primary care solutions
• Investigators: Principal Investigator: M. Julia Machline-Carrion, PhD, epHealth

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2023
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: November 14, 2022
• First Submitted That Met QC Criteria: November 14, 2022
• First Posted (Actual): November 21, 2022

Study Record Updates

• Last Update Posted (Estimated): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Atherosclerosis; Cardiovascular diseases; Dyslipidemias
• Additional Relevant MeSH Terms: Vascular Diseases; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Lipid Metabolism Disorders; Cardiovascular Diseases; Dyslipidemias; Atherosclerosis
• Other Study ID Numbers: CKJX839A1BR05R; 63520022.6.1001.0071 (Other Identifier: CAAE)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No