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

April 9, 2026 updated by: Hospital Israelita Albert Einstein

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1465

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Brazil
      • Belém, Brazil
        • Hospital Universitário João de Barros Barreto
      • Botucatu, Brazil
        • UPECLIN - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu
      • Curitiba, Brazil
        • Santa Casa de Curitiba
      • Fortaleza, Brazil
        • Centro de Pesquisas em Diabetes e Doenças Endócrino-Metabólicas
      • Goiânia, Brazil
        • Hospital Municipal de Aparecida de Goiânia
      • Goiânia, Brazil
        • Hospital Ruy Azeredo
      • Maceió, Brazil
        • Centro de Pesquisas Clínicas Dr Marco Mota
      • Natal, Brazil
        • Instituto Atena de Pesquisa Clinica
      • Osasco, Brazil
        • Unidade Hospital Municipal Antônio Giglio
      • Porto Alegre, Brazil
        • Hospital de Clínicas de Porto Alegre
      • Porto Alegre, Brazil
        • Santa Casa de Porto Alegre
      • Presidente Prudente, Brazil
        • Hospital Regional Presidente Prudente
      • Rio Branco, Brazil
        • Clínica Silvestre Santé
      • Rio de Janeiro, Brazil
        • Instituto Nacional de Cardiologia
      • São José, Brazil
        • Instituto de Cardiologia de Santa Catarina
      • São Paulo, Brazil
        • Hospital São Paulo (UNIFESP)
      • São Paulo, Brazil
        • Hospital São Paulo Universidade Federal de São Paulo
      • São Paulo, Brazil
        • Instituto de Cardiologia Dante Pazzanese
      • Vila Velha, Brazil
        • Hospital Evangélico de Vila Velha
    • Estado de Bahia
      • Salvador, Estado de Bahia, Brazil
        • Hospital da Bahia
    • Minas Gerais
      • Poços de Caldas, Minas Gerais, Brazil
        • Hospital Santa Lucía
    • Paraná
      • Campina Grande do Sul, Paraná, Brazil
        • Hospital e Maternidade Angelina Caron
    • Santa Catarina
      • Joinville, Santa Catarina, Brazil
        • Hospital Regional Hans Dieter Schmidt
    • Sergipe
      • Aracaju, Sergipe, Brazil
        • Centro de Pesquisa Clinica do Coracao
    • São Paulo
      • Bragança Paulista, São Paulo, Brazil
        • Hospital Universitário São Francisco de Assis
      • Campinas, São Paulo, Brazil
        • Instituto de Pesquisa clinica de Campinas
      • Marília, São Paulo, Brazil
        • Irmandade da Santa Casa de Misericórdia de Marília
      • Matão, São Paulo, Brazil
        • Hospital Carlos Fernando Malzoni

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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 ≤ 50 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Phase 1: LDL-C levels
Time Frame: Baseline
LDL-C levels measured at a single visit
Baseline
Phase 2: LDL-C
Time Frame: 6 months
LDL-C levels measured at the end of follow up of Phase 2
6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Phase 1: Prescribed lipid-lowering therapy
Time Frame: Baseline
Percentage of patients on prescribed lipid-lowering therapy
Baseline
Phase 1: Prescribed combination lipid-lowering therapy
Time Frame: Baseline
Percentage of patients on prescribed combination lipid-lowering therapy
Baseline
Phase 1: Prescribed intensive lipid-lowering therapy
Time Frame: Baseline
Percentage of patients on prescribed intensive lipid-lowering therapy
Baseline
Phase 1: Prescription of high intensity statins
Time Frame: Baseline
Percentage of prescription of high intensity statins
Baseline
Phase 1: Prescription of ezetimibe
Time Frame: Baseline
Percentage of prescription of ezetimibe
Baseline
Phase 1: LDL-C < 50 mg/dL
Time Frame: Baseline
Percentage of patients with LDL-C < 50 mg/dL
Baseline
Phase 1: Prescription of any statins
Time Frame: Baseline
Percentage of prescription of any statins
Baseline
Phase 1: Prescription of PCSK9 monoclonal antibody or siRNA PCSK9 inhibitors
Time Frame: Baseline
Percentage of prescription of PCSK9 monoclonal antibody or siRNA PCSK9 inhibitors
Baseline
Phase 2: Prescribed lipid-lowering therapy
Time Frame: 6 months
Percentage of patients on prescribed lipid-lowering therapy
6 months
Phase 2: Prescribed combination lipid-lowering therapy
Time Frame: 6 months
Percentage of patients on prescribed combination lipid-lowering therapy
6 months
Phase 2: Prescribed intensive lipid-lowering therapy
Time Frame: 6 months
Percentage of patients on prescribed intensive lipid-lowering therapy
6 months
Phase 2: Prescription of any statins
Time Frame: 6 months
Percentage of prescription of any statins
6 months
Phase 2: Prescription of high intensity statins
Time Frame: 6 months
Percentage of prescription of high intensity statins
6 months
Phase 2: Prescription of moderate intensity statins
Time Frame: 6 months
Percentage of prescription of moderate intensity statins
6 months
Phase 2: Prescription of low intensity statins
Time Frame: 6 months
Percentage of prescription of low intensity statins
6 months
Phase 2: Prescription of ezetimibe
Time Frame: 6 months
Percentage of prescription of ezetimibe
6 months
Phase 2: Prescription of PCSK9 monoclonal antibody or siRNA PCSK9 inhibitors
Time Frame: 6 months
Percentage of prescription of PCSK9 monoclonal antibody or siRNA PCSK9 inhibitors
6 months
Phase 2: LDL-C < 50 mg/dL
Time Frame: 6 months
Percentage of patients with LDL-C < 50 mg/dL
6 months
Phase 2: LDL-C relative change
Time Frame: 6 months
Change in LDL-C relative to baseline
6 months
Phase 2: LDL-C reduction of ≥50%
Time Frame: 6 months
Percentage of patients with LDL-C reduction of ≥50% relative to baseline
6 months
Phase 2: non-HDL-C relative change
Time Frame: 6 months
Change in non-HDL-C relative to baseline
6 months
Phase 2: Barriers for drug prescription
Time Frame: 6 months
Barriers for drug prescription at the system (cluster) and physician level
6 months
Phase 2: Adherence to prescribed lipid-lowering therapy
Time Frame: 6 months
Patient´s adherence to prescribed lipid-lowering therapy
6 months
Phase 2: Barriers for drug adherence
Time Frame: 6 months
Patient´s barriers for drug adherence
6 months
Phase 2: Intolerance to Statins
Time Frame: 6 months
Percentage of patients with intolerance to Statins
6 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Phase 2: 5P-MACE (Major Cardiovascular Events)
Time Frame: 6 months
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
6 months
Phase 2: 3P-MACE (Major Cardiovascular Events)
Time Frame: 6 months
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
6 months
Phase 2: Cardiovascular death
Time Frame: 6 months
Time to cardiovascular death
6 months
Phase 2: Death from any cause
Time Frame: 6 months
Time to death from any cause
6 months
Phase 2: Myocardial infarction
Time Frame: 6 months
Time to first myocardial infarction
6 months
Phase 2: Stroke
Time Frame: 6 months
Time to first stroke
6 months
Phase 2: Coronary revascularization
Time Frame: 6 months
Time to first coronary revascularization
6 months
Phase 2: Total deaths
Time Frame: 6 months
Total deaths within 6 months from inclusion
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hospital Israelita Albert Einstein

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Novartis
epHealth primary care solutions

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: M. Julia Machline-Carrion, PhD, epHealth

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 10, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 15, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 17, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 14, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 14, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 21, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 14, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 9, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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