Statin Adverse ReactionPhase 4NCT04453735
MUscle Side-Effects of Atorvastatin in Coronary Patients (MUSE) -Follow-up Study
A Phase 4 study testing Atorvastatin mylan 40 Mg Oral Tablet in people with Statin Adverse Reaction, run by Vestre Viken Hospital Trust at 2 sites in Norway.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Statin Adverse Reaction
- What is being tested?
- Atorvastatin mylan 40 Mg Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 2 sitesNorway
- Study dates
- 19 Aug 2020to 18 Dec 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
Norway2 sites
Vestre Viken HF, Drammen Hospital
Drammen, Buskerud, 3004
Hospital of Vestfold
Tønsberg, Vestfold, 3103
About this study
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
- Being tested
- Atorvastatin mylan 40 Mg Oral Tablet
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atorvastatin mylan 40 Mg Oral TabletDrug
Oral tablet on regular prescription
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Active comparator | Atorvastatin mylan 40 mg once daily Receives: Drug: Atorvastatin mylan 40 Mg Oral Tablet |
| Control | No intervention | No statin therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Measured: 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
Measured: 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.
Measured: 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.
Measured: 16 weeks following study start
Correlation between atorvastatin:HMGCR in PBMC vs. muscle. Correlation between atorvastatin:HMGCR in PBMC and the primary study endpoint.
Measured: 16 weeks following study start
Correlation between mevalonate pathway intermediates in muscle and the primary study endpoint. The ability of mevalonate pathway intermediates in muscle to differentiate confirmed SAMS and non-SAMS.
Measured: 16 weeks following study start
Correlation between mevalonate pathway intermediates in plasma vs. muscle and PBMC vs. muscle. Correlation between mevalonate pathway intermediates in blood and the primary study endpoint.
Measured: 16 weeks following study start
Correlation between mitochondrial respiratory enzymes in muscle and the primary study endpoint. The ability of mitochondrial respiratory enzymes in muscle to differentiate confirmed SAMS and non-SAMS.
Measured: 16 weeks following study start
Correlation between mitochondrial respiratory enzymes in PBMC vs. muscle. Correlation between mitochondrial respiratory enzymes in PMBC and the primary study endpoint.
Measured: 16 weeks following study start
Correlation between the FKBP1A:RyR1 ratio in muscle and the primary study endpoint. The ability of the FKBP1A:RyR1 ratio in muscle to differentiate confirmed SAMS and non-SAMS.
Measured: 16 weeks following study start
Correlation between the FKBP1A:RyR1 ratio in PBMC vs. muscle. Correlation between the FKBP1A:RyR1 ratio in PBMC and the primary study endpoint.
Measured: 16 weeks following study start
Correlation between caspase 3 signalling in muscle and the primary study endpoint. The ability of caspase 3 signalling in muscle to differentiate confirmed SAMS and non-SAMS.
Measured: 16 weeks following study start
Correlation between caspase 3 signalling in PBMC vs. muscle. Correlation between caspase 3 signalling in blood and the primary study endpoint.
Measured: 16 weeks following study start
Difference in muscle response variables between atorvastatin period and non-statin period.
Measured: 16 weeks following study start
Correlation of molecular effects in blood vs. muscle. Difference in blood response variables between atorvastatin period and non-statin period. Correlation between atorvastatin-related variables and response variables in blood.
Measured: 16 weeks following study start
Statin adherence measured with indirect methods and by parent drug and metabolite concentrations in blood
Measured: 16 weeks following study start
New-onset CHD symptoms. Intolerable muscle symptoms leading to discontinuation from the treatment arm. Creatine kinase (CK) > 10 times upper limit of the normal range or alaninaminotransferase (ALT) > 3 times upper normal limit
Measured: 16 weeks following study start
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2020
- Study start19 Aug 2020
- Primary completion18 Dec 2020
- Study completion18 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Statin Adverse ReactionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Prospective, open, intervention study
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vestre Viken Hospital Trust
- Sponsor type
- University, hospital or other
- Collaborators
- The Hospital of Vestfold, Oslo University Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04453735
- Sponsor's protocol ID
- REK 54041
- Status last verified
- Jun 2020
- First submitted
- 28 Jun 2020
- Last updated
- 26 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data will be made available for other researchers
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MUscle Side-Effects of Atorvastatin in Coronary Patients (MUSE) -Follow-up Study
- ClinicalTrials.gov ID
- NCT04453735
- Acronym / sponsor ID
- REK 54041
- Conditions
- Statin Adverse Reaction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Vestre Viken Hospital TrustUniversity, hospital or other
- Collaborators
- The Hospital of Vestfold, Oslo University Hospital
- Study start
- 19 Aug 2020 (actual)
- Primary completion
- 18 Dec 2020 (actual)
- Study completion
- 18 Dec 2020 (actual)
- First posted
- 1 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective, open, intervention study
| Arm | Type | Receives |
|---|---|---|
| Intervention | Active comparator | Drug: Atorvastatin mylan 40 Mg Oral TabletAtorvastatin mylan 40 mg once daily |
| Control | No intervention | –No statin therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atorvastatin mylan 40 Mg Oral TabletOral tablet on regular prescription | Drug | Intervention |
Primary outcome
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"
Time frame: 16 weeks following study start
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
17 secondary outcomes
The proportion of patients who report muscle symptoms on atorvastatin treatment and not on statin (dichotomous Statin Associated Muscle Symptom classification)
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 16 weeks following study start
Correlation between atorvastatin:HMGCR in PBMC vs. muscle. Correlation between atorvastatin:HMGCR in PBMC and the primary study endpoint.
Time frame: 16 weeks following study start
Correlation between mevalonate pathway intermediates in muscle and the primary study endpoint. The ability of mevalonate pathway intermediates in muscle to differentiate confirmed SAMS and non-SAMS.
Time frame: 16 weeks following study start
Correlation between mevalonate pathway intermediates in plasma vs. muscle and PBMC vs. muscle. Correlation between mevalonate pathway intermediates in blood and the primary study endpoint.
Time frame: 16 weeks following study start
Correlation between mitochondrial respiratory enzymes in muscle and the primary study endpoint. The ability of mitochondrial respiratory enzymes in muscle to differentiate confirmed SAMS and non-SAMS.
Time frame: 16 weeks following study start
Correlation between mitochondrial respiratory enzymes in PBMC vs. muscle. Correlation between mitochondrial respiratory enzymes in PMBC and the primary study endpoint.
Time frame: 16 weeks following study start
Correlation between the FKBP1A:RyR1 ratio in muscle and the primary study endpoint. The ability of the FKBP1A:RyR1 ratio in muscle to differentiate confirmed SAMS and non-SAMS.
Time frame: 16 weeks following study start
Correlation between the FKBP1A:RyR1 ratio in PBMC vs. muscle. Correlation between the FKBP1A:RyR1 ratio in PBMC and the primary study endpoint.
Time frame: 16 weeks following study start
Correlation between caspase 3 signalling in muscle and the primary study endpoint. The ability of caspase 3 signalling in muscle to differentiate confirmed SAMS and non-SAMS.
Time frame: 16 weeks following study start
Correlation between caspase 3 signalling in PBMC vs. muscle. Correlation between caspase 3 signalling in blood and the primary study endpoint.
Time frame: 16 weeks following study start
Difference in muscle response variables between atorvastatin period and non-statin period.
Time frame: 16 weeks following study start
Correlation of molecular effects in blood vs. muscle. Difference in blood response variables between atorvastatin period and non-statin period. Correlation between atorvastatin-related variables and response variables in blood.
Time frame: 16 weeks following study start
Statin adherence measured with indirect methods and by parent drug and metabolite concentrations in blood
Time frame: 16 weeks following study start
New-onset CHD symptoms. Intolerable muscle symptoms leading to discontinuation from the treatment arm. Creatine kinase (CK) > 10 times upper limit of the normal range or alaninaminotransferase (ALT) > 3 times upper normal limit
Time frame: 16 weeks following study start
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2021.
- Individual participant dataSharing planned: Yes. De-identified individual participant data will be made available for other researchers
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Atorvastatin mylan 40 Mg Oral Tablet in people with Statin Adverse Reaction, run by Vestre Viken Hospital Trust at 2 sites in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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" (time frame: 16 weeks following study start). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2021.