A clinical trial to evaluate efficacy, safety and cost-efficacy of gene analysis strategy in a population at risk of cardiovascular disease susceptible of receiving high or moderate-intensity doses of statins

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

5 Jun 2024 → ongoing

Decision date (initial)

2024-05-21

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic

To assess the efficacy of a statin preemptive genotyping strategy in reducing statin associated musculoskeletal adverse events.

Secondary objectives 6

1. To assess the efficacy of a statin preemptive genotyping strategy in optimizing dyslipidaemia management when compared to Standard of Care (SoC) treatment/dosing.
2. To assess the pharmacoeconomic feasibility of implementing a preemptive pharmacogenetic strategy to adverse musculoskeletal symptoms.
3. To identify novel prognostic and predictive genetic biomarkers of statin-related adverse events and efficacy.
4. To assess the efficacy of a statin preemptive genotyping strategy in reducing the major ischemic cardiovascular events.
5. To assess the effect of a statin preemptive genotyping strategy in improving patient therapeutic adherence
6. To assess the effect of a statin preemptive genotyping strategy in reducing perceived pain of SAMS

Conditions and MedDRA coding

Patients at risk of cardiovascular disease susceptible of receiving high or moderate-intensity doses of statins.

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 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.
2. Subject has voluntarily signed the ICF.
3. Subject must be ≥ 18 years old at the time of signing ICF.
4. Subject is able and willing to take part and be followed-up for the majority of the study duration.
5. Participants are susceptible to be prescribed any of the following: a. Atorvastatin ≥40 mg/day p.o. b. Simvastatin ≥20mg/day p.o. c. Pitavastatin≥2mg/day p.o. d. Rosuvastatin ≥40mg/day p.o. e. Pravastatin ≥40mg/day p.o. f. Lovastatin ≥40mg/day p.o. g. Fluvastatin ≥80 mg/day p.o.
6. Subjects must be naïve to any genotyping test of the following genes: SCLO1B1, ABCG2, CYP2C9, CYP3A4, CYP3A5 and HMGCR.
7. Subjects must be willing to comply and adhere to any treatment plan modifications established and to the procedures specified in this protocol.
8. 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.

Exclusion criteria 5

1. Subject is currently taking ubiquinone (Q10) supplements.
2. Known personal or family history of statin-associated autoimmune myopathy or HMG-CoA reductase disorder.
3. Pregnant or breastfeeding women
4. Subject has a personal history or analytical evidence of one of the following disorders: a. Any contraindications to statin administration as revealed in the summary of product characteristics (SmPCs) for statins. b. Prior SAMS if subject is not statin-naïve.
5. Any condition or situation deemed by the investigator precluding or interfering with the present study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. A composite variable that includes the incidence of patients with a clinically relevant statin-associated musculoskeletal symptom (defined as a combination of a SAMS-CI score ≥7 and a NPRS score ≥3) in the 9-month follow-up period or a serum CPK greater than three times the upper limit of normality prespecified by each centre’s laboratory, related to the statin.

Secondary endpoints 7

1. 9-month change in percentual LDLc defined as the percentage difference between LDLc values at 9 months minus baseline LDLc.
2. Percentage of patients that require either a statin dose modification/withdrawal or additional lipid-lowering therapy after 9 months in order to meet LDLc goals.
3. The difference between the costs of the intervention and all its surrounding procedures combined with the costs derived from the events in the intervention arm when compared to the costs derived from the events in the control arm alone over the 9-month follow-up period. Additionally, the ratio between cost differences and efficacy differences between both arms may be calculated.
4. Novel prognostic and predictive genetic biomarkers of statin-related adverse events and efficacy will be assessed in outlier subject’s/or any given subject for quality control reasons trough techniques not readily available at all centres, and only available at CNIO as well as genome-wide association studies when applicable. Aforementioned techniques may vary at CNIOs criteria and may include (but are not limited to) assays and/or next generation sequencing techniques.
5. Percentage of participants who experience a 4-component exploratory endpoint consisting of cardiovascular death, nonfatal myocardial infarction (MI), resuscitated cardiac arrest, or hospitalization for unstable angina
6. Difference in Morisky-Green (MMAS-8) questionnaire adherence levels/score between both study arms.
7. Difference in Numeric Pain Rating Scale (NPRS) score between both study arms. Categories will be as follow: 0-3 no pain; 3-5 moderate pain; 5-7 intense pain; 7-9 very intense pain; 9-10 extreme pain.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz

Sponsor organisation

Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz

Address

Paseo Castellana 261

City

Madrid

Postcode

28046

Country

Spain

Scientific contact point

Organisation

Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz

Contact name

Alberto M. Borobia

Public contact point

Organisation

Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz

Contact name

Alberto M. Borobia

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications