Efficacy, Safety and Cost-efficacy of a Pre-emptive Genotyping Strategy in Patients Receiving Statins

NCT06262685 | Unknown Phase 4

• 1 other identifier: 2023-509418-12-00
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase IV multicentre adaptive single-blinded randomized clinical trial if preemptively genotyping populations at risk of cardiovascular disease susceptible of receiving high or moderate doses of statin therapy is efficacious, cost-efficacious, and feasible within the Spanish National Health System when compared to the current standard of care. This trial is nested within the iPHARMGx master protocol

Conditions

Cardiovascular Diseases; Dyslipidemias; Statin Adverse Reaction; Pharmacogenic Myopathy

Keywords

Statin; Statin Associated Muscle Symptoms; Cardiovascular disease; Cost-effectiveness; Phase IV Clinical Trial; Pharmacogenetic

Outcome Measures

Primary Outcomes (1)

• Incidence of clinically relevant statin-associated musculoskeletal events

  As defined by the a composite endpoint: Patients with a clinically relevant statin-associated musculoskeletal symptom defined as a combination of a SAMS-CI (Statin Associated Muscular Symptoms Clinical Index) score ≥7 points and a NPRS (Numerical Pain Rating Scale) score ≥3) in the 9-month follow-up period Serum creatin phosphokinase (CPK) \[UI/L\] greater than three times the upper limit of normality prespecified by each centre's laboratory, in relation to the statin.

  9-months

Secondary Outcomes (3)

• Low density lipoprotein cholesterol (LDLc) serum concentration baseline reduction rate

  9-months

• Baseline change in statin therapy prescription

  9-months

• Cost of a statin preemptive pharmacogenetic prescription scheme

  Though study completion, on average 18 months

Other Outcomes (4)

• Novel prognostic and predictive genetic biomarkers of statin-related adverse events and efficacy identification

  Though study completion, on average 18 months

• Death from cardiovascular causes, nonfatal myocardial infarction or hospitalization for unstable angina or resuscitated cardiac arrest

  9-months

• Difference in percentage in the eight-item Morisky Medication Adherence Scale (MMAS-8) questionnaire score between intervention and control arm

  9-months

Study Arms (2)

Experimental Group

EXPERIMENTAL

Patients in this Experimental Group will receive any of the statins authorized in Spain for lipid-lowering, both for primary and secondary prevention. Subjects in the Experimental Group will be administered the specific type and dosage of statins recommended by the Clinical Pharmacogenetics Consortium's genotype guidelines, utilizing the patient's pharmacogenetic information and characteristics

Other: Preemptive pharmacogenetic atorvastatin dose based on CPIC guidelines; Other: Preemptive pharmacogenetic simvastatin dose based on CPIC guidelines; Other: Preemptive pharmacogenetic pitavastatin dose based on CPIC guidelines; Other: Preemptive pharmacogenetic rosuvastatin dose based on CPIC guidelines; Other: Preemptive pharmacogenetic pravastatin dose based on CPIC guidelines; Other: Preemptive pharmacogenetic lovastatin dose based on CPIC guidelines; Other: Preemptive pharmacogenetic fluvastatin dose based on CPIC guidelines

Control Group

ACTIVE COMPARATOR

Patients in this Control Group will receive any of the authorized statins in Spain for lipid-lowering, whether for primary or secondary prevention. They will be administered statins according to clinical practice and the drug's product labeling, without exceeding the already authorized dosages

Other: Standard of Care (SoC) dosing of atorvastatin; Other: Standard of Care (SoC) dosing of simvastatin; Other: Standard of Care (SoC) dosing of pitavastatin; Other: Standard of Care (SoC) dosing of rosuvastatin; Other: Standard of Care (SoC) dosing of prasavastatin; Other: Standard of Care (SoC) dosing of lovastatin; Other: Standard of Care (SoC) dosing of fluvastatin

Interventions

Preemptive pharmacogenetic atorvastatin dose based on CPIC guidelines OTHER

Atorvastatin at the dosage reccomended by the 2022 "Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and considerations for Statin-Associated Musculoskeletal Symptoms" based on the subjects pharmacogenetic phenotype. A comprehensive description of said doses are can be accessed at: https://cpicpgx.org/guidelines/cpic-guideline-for-statins/

Experimental Group

Preemptive pharmacogenetic simvastatin dose based on CPIC guidelines OTHER

Simvastatin at the dosage reccomended by the 2022 "Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and considerations for Statin-Associated Musculoskeletal Symptoms" based on the subjects pharmacogenetic phenotype. A comprehensive description of said doses are can be accessed at: https://cpicpgx.org/guidelines/cpic-guideline-for-statins/

Experimental Group

Preemptive pharmacogenetic pitavastatin dose based on CPIC guidelines OTHER

Pitavastatin at the dosage reccomended by the 2022 "Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and considerations for Statin-Associated Musculoskeletal Symptoms" based on the subjects pharmacogenetic phenotype. A comprehensive description of said doses are can be accessed at: https://cpicpgx.org/guidelines/cpic-guideline-for-statins/

Experimental Group

Preemptive pharmacogenetic rosuvastatin dose based on CPIC guidelines OTHER

Rosuvastatin at the dosage reccomended by the 2022 "Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and considerations for Statin-Associated Musculoskeletal Symptoms" based on the subjects pharmacogenetic phenotype. A comprehensive description of said doses are can be accessed at: https://cpicpgx.org/guidelines/cpic-guideline-for-statins/

Experimental Group

Preemptive pharmacogenetic pravastatin dose based on CPIC guidelines OTHER

Pravastatin at the dosage reccomended by the 2022 "Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and considerations for Statin-Associated Musculoskeletal Symptoms" based on the subjects pharmacogenetic phenotype. A comprehensive description of said doses are can be accessed at: https://cpicpgx.org/guidelines/cpic-guideline-for-statins/

Experimental Group

Preemptive pharmacogenetic lovastatin dose based on CPIC guidelines OTHER

Lovastatin at the dosage reccomended by the 2022 "Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and considerations for Statin-Associated Musculoskeletal Symptoms" based on the subjects pharmacogenetic phenotype. A comprehensive description of said doses are can be accessed at: https://cpicpgx.org/guidelines/cpic-guideline-for-statins/

Experimental Group

Preemptive pharmacogenetic fluvastatin dose based on CPIC guidelines OTHER

Fluvastatin at the dosage reccomended by the 2022 "Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and considerations for Statin-Associated Musculoskeletal Symptoms" based on the subjects pharmacogenetic phenotype. A comprehensive description of said doses are can be accessed at: https://cpicpgx.org/guidelines/cpic-guideline-for-statins/

Experimental Group

Standard of Care (SoC) dosing of atorvastatin OTHER

Subject allocated to this arm will receive the atorvastatin according to clinical practice and the drug's product labelling, and never exceeding the already authorized dosages. These subject will not receive a personalised dosed/prescription based on their pharmacogenetic phenotype

Control Group

Standard of Care (SoC) dosing of simvastatin OTHER

Subject allocated to this arm will receive the simvastatin according to clinical practice and the drug's product labelling, and never exceeding the already authorized dosages. These subject will not receive a personalised dosed/prescription based on their pharmacogenetic phenotype

Control Group

Standard of Care (SoC) dosing of pitavastatin OTHER

Subject allocated to this arm will receive the pitavastatin according to clinical practice and the drug's product labelling, and never exceeding the already authorized dosages. These subject will not receive a personalised dosed/prescription based on their pharmacogenetic phenotype

Control Group

Standard of Care (SoC) dosing of rosuvastatin OTHER

Subject allocated to this arm will receive the rosuvastatin according to clinical practice and the drug's product labelling, and never exceeding the already authorized dosages. These subject will not receive a personalised dosed/prescription based on their pharmacogenetic phenotype

Control Group

Standard of Care (SoC) dosing of prasavastatin OTHER

Subject allocated to this arm will receive the prasavastatin according to clinical practice and the drug's product labelling, and never exceeding the already authorized dosages. These subject will not receive a personalised dosed/prescription based on their pharmacogenetic phenotype.

Control Group

Standard of Care (SoC) dosing of lovastatin OTHER

Subject allocated to this arm will receive the lovastatin according to clinical practice and the drug's product labelling, and never exceeding the already authorized dosages. These subject will not receive a personalised dosed/prescription based on their pharmacogenetic phenotype.

Control Group

Standard of Care (SoC) dosing of fluvastatin OTHER

Subject allocated to this arm will receive the fluvastatin according to clinical practice and the drug's product labelling, and never exceeding the already authorized dosages. These subject will not receive a personalised dosed/prescription based on their pharmacogenetic phenotype.

Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Each potential participant must satisfy all of the following criteria to be enrolled in the study:
• Ability of the participant to understand the purpose and risks of the study, to provide informed consent, and to authorize the use of confidential health information in accordance with national and local privacy regulations.
• Subject has voluntarily signed the ICF.
• Subject must be ≥ 18 years old at the time of signing ICF.
• Subject is able and willing to take part and be followed-up for the majority of the study duration.
• Participants are susceptible to be prescribed any of the following:
• Atorvastatin ≥40 mg/day p.o.
• Simvastatin ≥20mg/day p.o.
• Pitavastatin≥2mg/day p.o.
• Rosuvastatin ≥40mg/day p.o.
• Pravastatin ≥40mg/day p.o.
• Lovastatin ≥40mg/day p.o.
• Fluvastatin ≥80 mg/day p.o.
• Subjects must be naïve to any genotyping test of the following genes: SCLO1B1, ABCG2, CYP2C9, CYP3A4, CYP3A5 and HMGCR.
• Subjects must be willing to comply and adhere to any treatment plan modifications established and to the procedures specified in this protocol.

You may not qualify if:

• Any potential participant who meets any of the following criteria will be excluded from participating in the study:
• Subject is currently taking ubiquinone (Q10) supplements.
• Known personal or family history of statin-associated autoimmune myopathy or HMG-CoA reductase disorder.
• Pregnant or breastfeeding women
• Subject has a personal history or analytical evidence of one of the following disorders:
• Any contraindications to statin administration as revealed in the summary of product characteristics (SmPCs) for statins.
• Prior SAMS if subject is not statin-naïve.
• Any condition or situation deemed by the investigator precluding or interfering with the present study.

Sponsors & Collaborators

• Instituto de Investigación Hospital Universitario La Paz: lead
• Instituto de Salud Carlos III: collaborator

Study Sites (1)

Hospital La Paz

Madrid, Madrid, 28046, Spain

Location

Related Publications (1)

• Stewart S, Seco-Meseguer E, Diago-Sempere E, Marin-Candon A, Carmona M, Estebanez M, Lopez-Fernandez LA, Imaz-Iglesia I, Del Mar Garcia Saiz M, Laserna-Mendieta EJ, Peiro AM, Farre M, Rodriguez-Jimenez C, Saiz-Rodriguez M, Sanabria-Cabrera J, Rosas-Alonso R, Abad-Santos F, Pedrosa L, Carcas AJ, Garcia Garcia I, Borobia AM; iPHARMGx study group. Phase IV adaptive randomised clinical trials evaluating efficacy and cost-efficacy of pre-emptive pharmacogenetic genotyping strategies in the Spanish National Health System: iPHARMGx Master Protocol and PREVESTATGx nested clinical trial. BMJ Open. 2024 Nov 7;14(11):e089823. doi: 10.1136/bmjopen-2024-089823.

  PMID: 39510769 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Dyslipidemias; Malignant fever

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Central Study Contacts

Alberto M. Borobia Pérez, MD, PhD

CONTACT

+34 912071466; alberto.borobia@salud.madrid.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Subjects will remain blinded to arm assigned because pharmacogenetic phenotype and statin/dose-guidance will only be exclusively accesible to the attending physician
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase IV, multicentre, controlled, randomized, parallel and single-blind adaptive clinical trial nested within the iPHARMGx master protocol study

Study Record Dates

• First Submitted: January 9, 2024
• First Posted: February 16, 2024
• Study Start: March 4, 2024
• Primary Completion: February 10, 2025
• Study Completion: March 4, 2025
• Last Updated: February 16, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available at the same time as the results will be published, and will be kept available to everyone without any time limit.
• Access Criteria: Data will be available indefinitely on the publisher's website, as long as it is kept by the Publisher, for anyone who wishes to access the data, for non-commercial purposes

Locations

ES (1)