The DEtermining Statin Intolerance FOr Rosuvastatin (DESIFOR) Trial

Study Overview
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Brief Summary
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This study will enroll patients who previously were not able to tolerate being on a statin medication due to muscle-related side effects. Research has shown that many people who have muscle symptoms on statin therapy do not experience the same side effects if they try it again later. This study is part of a larger effort to: See how common it is for patients to still be intolerant of statin medication after trying it a second time; and For those patients who do tolerate being on a statin after trying it a second time, see how common it is for them to still be taking the statin 3 months after completing the main part of the study. Patients who agree to participate will be given a 5 month randomly allocated supply of statin and placebo and track their symptoms weekly.

Detailed Description
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This study is a single center, double-blinded randomized controlled trial for patients eligible for statin therapy by current guidelines, but not on statin therapy due to a history of statin intolerance. Patients will be provided a DESIFOR kit which includes 5 randomly allocated 4-week blister packs of capsules containing either 20mg of rosuvastatin or placebo. While blinded to treatment, patients will document the severity of musculoskeletal symptoms every week using a numerical scale. The primary endpoint will be the difference between the mean musculoskeletal symptom score while randomized to statin therapy compared to the mean score while on placebo. After completion of the study, the results will be unblinded and reviewed at a 6 month follow-up visit with the patient and, for patients with symptoms found to not correlate with statin therapy, a trial of non-blinded statin therapy over the next 3 months will be recommended. This study will serve as a pilot study to determine the feasibility and potential benefits of a larger multicenter trial with similar aims.

Official Title
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The DEtermining Statin Intolerance FOr Rosuvastatin (DESIFOR) Trial

Conditions
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Cardiovascular Risk Factor, Cardiovascular Diseases, Adverse Effect

Intervention / Treatment
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* Drug: Rosuvastatin 20mg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults age 21-75 years old Statin eligible according to the 2013 ACC/AHA cholesterol guidelines, including individuals with: Known ASCVD Diabetes LDL-C > 190mg/dl 10-year ASCVD risk >7.5% Statin intolerant Defined by discontinuation of at least 2 separate statins due to potential musculoskeletal side effects Exclusion Criteria: Women who are pregnant, nursing or attempting to become pregnant. Individuals deemed to be at very high CVD risk and therefore appropriate for a PCSK9 inhibitor including: Individuals with familial hypercholesterolemia with markedly elevated LDL-C levels Individuals with known ASCVD and recurrent events Individuals who are not otherwise clinically indicated to take 20mg rosuvastatin Individuals who experienced severe reactions in the past, including: Rhabdomyolysis Severe myositis Anaphylaxis

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Patients will serve as their own controls in this study whereby they will receive randomly allocated 28-day packets of statin and placebo.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rosuvastatin 20mg<br>Each participant will receive a 3 month randomly allocated supply of this medication preceded by a 7 day wash-out period. | Drug: Rosuvastatin 20mg<br>* Statin Therapy<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Placebo<br>|
| No Intervention: No Treatment<br>7 day wash-out period between months | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Musculoskeletal intolerance (as documented in study assessments) | Prevalence of musculoskeletal intolerance between the groups, defined by a lack of statistical difference in the mean musculoskeletal symptom score while on statin therapy compared to placebo, in patients previously identified as statin intolerant. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Statin Utilization | Number of individuals taking statins 3 months post study | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High ASCVD Risk, Statin Therapy, Prevention