ATORVASTATIN for Coronary artery disease

Inclusion criteria

• {"criterion_text":"-Men aged 45-80 on 1st of January 2025"}
• {"criterion_text":"-Women aged 55-80 on 1st of January 2025"}
• {"criterion_text":"-CAD PRS top 20% confirmed by the Estonian Biobank"}
• {"criterion_text":"-The family physician of the study participant has been contracted to participate in the trial."}
• {"criterion_text":"-Written informed consent has been provided to participate in the trial"}

Exclusion criteria

• {"criterion_text":"-\tDiagnosed with ischemic heart disease (I20–I25), stroke or transient ischemia (I60–64, I69, G45), peripheral vascular occlusion (I65–66, I67.2, I70, I73.9), diseases of liver (K70-K77), end stage renal disease (N18.0), mental and behavioural disorders due to psychoactive substance use (F10-F19). \tThe diagnosis must be present at least 2 times on a health claim or prescription within at least a 6-month period between 1.01.2022-31.12.2024."}
• {"criterion_text":"-\tCurrently using statin treatment: \tThe individual has at least 1 prescription from ATC groups C10AA or C10BA between 01.01.2022- 31.12.2024. \tThe individual has answered in the recruitment call that he/she is currently using statins or has been prescribed statins in the past 3 years."}
• {"criterion_text":"-\tCo-morbid physical or mental illnesses that prevent the individual from granting consent or participating in the trial (according to the judgement of the investigator)."}
• {"criterion_text":"-\tIndividuals taking: \t a combination of sofosbuvir/velpatasvir/voxilaprevir (used to treat hepatitis C); \t ciclosporin \t fusidic acid orally or by injection."}
• {"criterion_text":"-\tHas familiar hypercholesterolemia (APOB, PCSK9, LDLR genes verified by the Estonian biobank)"}
• {"criterion_text":"-\tIs currently participating in other clinical trials."}
• {"criterion_text":"-\tHas been taking investigative trial medication during the past 30 days prior to study inclusion."}
• {"criterion_text":"-\tIndividuals with a substance abuse disorder (alcohol, narcotic substances)."}
• {"criterion_text":"-\tIndividuals with hypersensitivity to the active substance (rosuvastatin or atorvastatin) or its excipients."}

Primary endpoints

• {"endpoint_text":"-Time to the first occurrence of Major Adverse Cardiovascular Events (MACE), ICD-10 codes: ischaemic heart disease (I20–I25), stroke or transient ischemia (I60–64, I69, G45), peripheral vascular occlusion (I65–66, I67.2, I70, I73.9), revascularization (Z95.1, Z95.5, Z95.8, Z95.9) or cardiovascular death (I00-78) from baseline.","definition_or_measurement_approach":"Time-to-event outcome measured from baseline defined by first occurrence of the listed ICD-10 codes (MACE components) or cardiovascular death."}

Secondary endpoints

• {"endpoint_text":"-Incidence rate of death from any cause among the study participants.","definition_or_measurement_approach":"Measured as incidence rate of all-cause mortality among study participants during follow-up."}
• {"endpoint_text":"-Change in CVD risk factors from baseline (LDL-cholesterol, blood pressure, BMI, waist circumference, smoking, alcohol consumption prevalence) by the end of the trial in the intervention and control arm.","definition_or_measurement_approach":"Measured change from baseline in listed cardiovascular risk factors by end of trial in each arm."}
• {"endpoint_text":"-Treatment adherence in the intervention arm based on prescriptions and purchases of statins (C10AA, C10BA) and self-reporting using the MARS-5 scale.","definition_or_measurement_approach":"Adherence assessed via prescription/purchase records (ATC C10AA/C10BA) and self-reported MARS-5 questionnaire."}
• {"endpoint_text":"-Fidelity of implementation assessed by participant feedback, and adherence to program activities (record analysis).","definition_or_measurement_approach":"Assessment via participant feedback and program activity records to evaluate fidelity of implementation."}
• {"endpoint_text":"-Acceptability of the primary prevention program across study participants.","definition_or_measurement_approach":"Measured using participant-reported acceptability assessments."}
• {"endpoint_text":"-Satisfaction with study processes and results.","definition_or_measurement_approach":"Measured via participant-reported satisfaction assessments."}
• {"endpoint_text":"-Difference in plasma concentrations of rosuvastatin comparing study participants with and without a mutation in the SLCO1B1, ABCG2, CYP2C9, CYP2C19, UGT-d, SLCO1B3, SLCO2B1, ABCC2, ABCB11 genes.","definition_or_measurement_approach":"Comparison of measured plasma rosuvastatin concentrations between participants with and without specified gene mutations."}
• {"endpoint_text":"-Difference in rosuvastatin side effects between study participants with and without a mutation in the SLCO1B1, ABCG2, CYP2C9, CYP2C19, UGT-d, SLCO1B3, SLCO2B1, ABCC2, ABCB11 genes.","definition_or_measurement_approach":"Comparison of adverse effect rates related to rosuvastatin between genetic subgroups."}
• {"endpoint_text":"-Difference in side effects and overall trial outcomes depending on gut microbiome composition and functionality.","definition_or_measurement_approach":"Assessment of relationship between gut microbiome composition/function and side effects/outcomes."}
• {"endpoint_text":"-Utilisation of healthcare resources (non-trial physician and cardiologist visits, hospitalizations, length of stay, health care and informal resource use, direct healthcare costs.)","definition_or_measurement_approach":"Measured healthcare resource utilisation and associated direct costs during follow-up."}
• {"endpoint_text":"-Number of participants with adverse events and serious adverse events from statin therapy.","definition_or_measurement_approach":"Count of participants experiencing adverse events and SAEs attributed to statin therapy."}
• {"endpoint_text":"-Number of participants who withdrew or dropped out from the study.","definition_or_measurement_approach":"Count of participant withdrawals and drop-outs during the study."}
• {"endpoint_text":"-Utilities from the EQ-5L-5D surveys and productivity costs from the iPCQ survey for calculating quality-adjusted life years (QALY) gained over a lifetime, incremental cost-effectiveness ratio (ICER).","definition_or_measurement_approach":"Health utility and productivity data from EQ-5D-5L and iPCQ to model lifetime QALYs and calculate ICER."}

Methods

• Contacting Estonian Biobank participants (CAD PRS top 20%) via email
• Contacting Estonian Biobank participants via SMS
• Gene donor portal messaging (intro text) to Estonian Biobank participants
• Recruitment phone calls (recruitment call used to confirm current statin use)
• Recruitment through contracted family physicians in Estonia

Estonia

Earliest CTIS Part Ii Submission Date

18-12-2024

Latest Decision Or Authorization Date

19-12-2024

Processing Time Days

1

Number Of Sites

2

Number Of Participants

2500

Primary sponsor

Full Name

University Of Tartu

Organisation Type

Educational Institution

Country Of Registered Address

Estonia