A Multicenter, Controlled, Randomized, Single-blind Phase IV Trial Assesses Efficacy, Safety, and Cost of Pre-emptive Genotyping in a Cardiovascular Risk Population Eligible for High/Moderate-intensity Statins
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 216
- 试验地点
- 2
- 主要终点
- Incidence of clinically relevant statin-associated musculoskeletal events
研究概览
简要总结
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
详细描述
This is a nation-wide, multicentre, randomised, controlled, and adaptive phase IV clinical trial that aims to assess the efficacy and cost-efficacy of pre-emptive pharmacogenetic testing strategies, including those impacted by genetic variants associated with adverse drug reactions (ADRs) or limited efficacy. Populations at high-risk of developing clinically relevant outcomes will be enrolled in nested trials within this master protocol. The clinical trials will evaluate the efficacy and cost-efficacy of pre-emptive genotyping by defining a drug-gene-endpoint triad. Study subjects will be pre-emptively genotyped and, if found to have an actionable gene variant, randomly allocated to either a test group where guideline-based treatment modifications will be initiated or a control group that will be managed according to healthcare provider standard of care (SoC). Subsequently, subjects will be prospectively followed at prespecified timepoints. Detailed information on drug-gene-endpoint triads, allocation schemes, and follow-up visits will be provided in each of the subprotocols. A Data Monitoring Committee (DMC), composed of physician experts, will be appointed for each nested trial to review the data on an ongoing basis, ensuring the safety of participants and scientific validity of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
Subjects will remain blinded to arm assigned because pharmacogenetic phenotype and statin/dose-guidance will only be exclusively accesible to the attending physician
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Women of childbearing potential must commit not to become pregnant. Subjects must be willing to use highly effective contraceptive methods or have practiced sexual abstinence during the study.
排除标准
- •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.
研究组 & 干预措施
Control Group
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
干预措施: Standard of Care (SoC) dosing of lovastatin (Other)
Experimental Group
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
干预措施: Preemptive pharmacogenetic atorvastatin dose based on CPIC guidelines (Other)
Experimental Group
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
干预措施: Preemptive pharmacogenetic simvastatin dose based on CPIC guidelines (Other)
Experimental Group
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
干预措施: Preemptive pharmacogenetic pitavastatin dose based on CPIC guidelines (Other)
Experimental Group
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
干预措施: Preemptive pharmacogenetic rosuvastatin dose based on CPIC guidelines (Other)
Experimental Group
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
干预措施: Preemptive pharmacogenetic pravastatin dose based on CPIC guidelines (Other)
Experimental Group
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
干预措施: Preemptive pharmacogenetic lovastatin dose based on CPIC guidelines (Other)
Experimental Group
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
干预措施: Preemptive pharmacogenetic fluvastatin dose based on CPIC guidelines (Other)
Control Group
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
干预措施: Standard of Care (SoC) dosing of atorvastatin (Other)
Control Group
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
干预措施: Standard of Care (SoC) dosing of simvastatin (Other)
Control Group
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
干预措施: Standard of Care (SoC) dosing of pitavastatin (Other)
Control Group
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
干预措施: Standard of Care (SoC) dosing of rosuvastatin (Other)
Control Group
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
干预措施: Standard of Care (SoC) dosing of prasavastatin (Other)
Control Group
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
干预措施: Standard of Care (SoC) dosing of fluvastatin (Other)
结局指标
主要结局
Incidence of clinically relevant statin-associated musculoskeletal events
时间窗: 9-months
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.
次要结局
- Cost of a statin preemptive pharmacogenetic prescription scheme(Though study completion, on average 18 months)
- Low density lipoprotein cholesterol (LDLc) serum concentration baseline reduction rate(9-months)
- Baseline change in statin therapy prescription(9-months)