MUscle Side-Effects of Atorvastatin in Coronary Patients (MUSE) -Follow-up Study

NCT04453735 | Completed Phase 4

• 1 other identifier: REK 54041
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

Statins are cornerstone treatment in secondary cardiovascular disease (CVD) prevention. Today, statin non-adherence (patients not taking their prescribed drug) remains a major public health concern, leading to adverse outcomes in terms of morbidity, mortality and healthcare costs. The principal reason for statin non-adherence and discontinuation is statin-associated muscle symptoms (SAMS). Objective SAMS diagnostics do not exist. We aim to unravel the pathophysiology of SAMS and develop diagnostic tools to differentiate real SAMS from muscle symptoms not related to the statin, among coronary patients with self-perceived SAMS. In this follow-up study we aims to determine the effect of 7 weeks open treatment with atorvastatin 40 mg/day, followed by 7 weeks open treatment with no lipid lowering treatment, on muscle symptom intensity in patients classified with confirmed statin-associated muscle symptoms (SAMS) (i.e. statin-dependent muscle side-effects) and non-SAMS in the MUscle Side-Effects of atorvastatin in coronary patients (MUSE) randomized double blinded cross-over trial. We have developed novel methods that will be used to measure atorvastatin metabolites and drug effect biomarkers directly in skeletal muscle and blood . The diagnostic accuracy of these biomarkers to differentiate real SAMS from non-SAMS will be evaluated. A new diagnostic tool may potentially be implemented to assess SAMS in the individual patient and enable personalized follow-up. It may also represent an important tool in the communication with patients misattributing their muscle symptoms to statins. The long-term results may be better quality of life and reduced morbidity, mortality and healthcare costs.

Conditions

Statin Adverse Reaction

Outcome Measures

Primary Outcomes (1)

• Individual mean difference in muscular symptom intensity measured with a 0 (no symptoms) to 10 (worst imaginable symptoms) Visual Analogue Scale (VAS) score between treatment periods with statin and "no statin treatment"

  Individual mean difference in muscular symptom (i.e. pain, aching, tenderness, stiffness, cramp and/or weakness) intensity between treatment periods with statin and no statin, reported by the patients over the last three weeks (i.e. week 4-7) measured with a 0 (no symptoms) to 10 (worst imaginable symptoms) Visual Analogue Scale (VAS) score with aggregated data from each subscale

  16 weeks following study start

Secondary Outcomes (17)

• The proportion of patients who report muscle symptoms on atorvastatin treatment and not on statin (dichotomous Statin Associated Muscle Symptom classification)

  16 weeks following study start

• Correlation between atorvastatin-related variables in muscle and the primary study endpoint. The ability of atorvastatin-related variables in muscle to differentiate confirmed SAMS and non-SAMS

  16 weeks following study start

• Correlation between atorvastatin-related variables in plasma vs. muscle and PBMC vs. muscle. Correlation between atorvastatin-related variables in blood and the primary study endpoint.

  16 weeks following study start

• Correlation between atorvastatin: HMGCR in muscle and the primary study endpoint. The ability of atorvastatin:HMGCR in muscle to differentiate confirmed SAMS and non-SAMS.

  16 weeks following study start

• Correlation between atorvastatin:HMGCR in PBMC vs. muscle. Correlation between atorvastatin:HMGCR in PBMC and the primary study endpoint.

  16 weeks following study start

Study Arms (2)

Intervention

ACTIVE COMPARATOR

Atorvastatin mylan 40 mg once daily

Drug: Atorvastatin mylan 40 Mg Oral Tablet

Control

NO INTERVENTION

No statin therapy

Interventions

Atorvastatin mylan 40 Mg Oral Tablet DRUG

Oral tablet on regular prescription

Intervention

Eligibility Criteria

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

You may qualify if:

• Participation in the MUSE trial (Eudract nr. 2018-004261-14) and still fulfilling the study entry criteria: First or recurrent diagnosis (myocardial infarction) or treatments (PCI or CABG) for a CHD event 12-42 months prior to study start.

You may not qualify if:

• First or recurrent diagnosis (myocardial infarction) or treatments (PCI or CABG) for a CHD event the a) past 12 months prior to study start in high risk patients (i.e. at least one of following comorbid conditions: systolic heart failure, \>1 previous myocardial infarction, kidney failure, diabetes, and smokers) and b) the past 6 months prior to study start in low risk patients without any of the co-morbid conditions mentioned above and in patients who are not taking a statin at all.
• Patients with symptomatic peripheral artery disease and patients with familial hypercholesterolemia
• Patient has any contraindications for atorvastatin listed in the Summary of Product Characteristics (i.e. known hypersensitivity to the ingredients, acute liver failure/ ALT \> 3 times upper limit of the normal range in blood at study start, pregnancy and breastfeeding )
• History of previous rhabdomyolysis, myopathy or liver failure due to statin treatment with CK \> 10 times upper limit of the normal range or ALT \> 3 times upper limit of the normal range.
• Any condition (e.g. psychiatric illness, dementia) or situation, that in the investigator's opinion could put the subject at significant risk, confound the study results, interfere significantly with the subject participation in the study, or rendering informed consent unfeasible
• Short life expectancy (\<12 months) due to other medical conditions
• Not being able to understand Norwegian.
• Women of childbearing potential defined as all premenopausal female.
• Participation in another randomized clinical trial
• Classified with significantly more muscle symptoms on placebo than on atorvastatin in the MUSE trial

Sponsors & Collaborators

• Vestre Viken Hospital Trust: lead
• The Hospital of Vestfold: collaborator
• Oslo University Hospital: collaborator

Study Sites (2)

Vestre Viken HF, Drammen Hospital

Drammen, Buskerud, 3004, Norway

Location

Hospital of Vestfold

Tønsberg, Vestfold, 3103, Norway

Location

MeSH Terms

Interventions

Tablets

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, open, intervention study

Study Record Dates

• First Submitted: June 28, 2020
• First Posted: July 1, 2020
• Study Start: August 19, 2020
• Primary Completion: December 18, 2020
• Study Completion: December 18, 2020
• Last Updated: February 26, 2021

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be available within 5 years of study completion

Locations

NO (2)