DESIFOR-EXPAND (MHIF)

The DEterminig Statin Intolerance for Rosuvastatin Trial

The DESIFOR pilot study was conducted to determine the feasibility of utilizing an n-of-1 trial to facilitate tolerance of unblinded rosuvastatin in patients with prior statin intolerance

Study Overview

• Status: Recruiting
• Conditions: Statin Adverse Reaction; Statin; Statin Therapy
• Intervention / Treatment: Drug: Rosuvastatin (Crestor); Drug: Placebo

Detailed Description

Recently developed lipid lowering therapies have been shown to significantly reduce LDL cholesterol and subsequent CVD risk (1, 2). However, they are expensive, and the cost-effectiveness of these medications remains controversial, especially in primary prevention. Novel lipid lowering therapies are frequently considered for individuals with statin intolerance, but payers frequently deny prescription for these medications due to lack of adequate proof of true statin intolerance. How to accurately determine statin intolerance remains a clinical conundrum for both patients and providers. A more scientific, definitive method to determine statin intolerance could potentially allow appropriate, cost-effective use of statin therapy in individuals found to not actually be statin intolerant as well as judicious use of novel medications in patients who are found to truly be statin intolerant.

The DESIFOR pilot study was conducted to determine the feasibility of utilizing an n-of-1 trial to facilitate tolerance of unblinded rosuvastatin in patients with prior statin intolerance. The DESIFOR pilot study was a single-center, randomized, double-blinded, n-of-1 trial in patients aged 21 to 79 years and eligible for statin therapy by current guidelines but not on therapy due to intolerance of >2 statins. Using a double-blinded, N-of-1 randomized trial in patients with previous statin intolerance, <10% of patients had data suggestive of true statin intolerance, and 2/3 of patients were subsequently able to tolerate 3-months of unblinded treatment with rosuvastatin (3). These data raise the hypothesis that an n-of-1 trial can be used to facilitate tolerance of unblinded rosuvastatin in patients with prior statin intolerance.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Gretchen Program Director, RDN, CDCES; Phone Number: 612-863-3383; Email: Gbenson@mhif.org

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Recruiting
      • Minneapolis Heart Institute Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients (≥ 21 years old) with a prior history of statin intolerance. Statin intolerance is defined by discontinuation of at least 2 different statin medications due to possible side effects. Patients can participate in the trial while on other lipid-lowering agents, such as ezetimibe and PSCK9 inhibitors, as long as the patient has been on the other lipid lowering therapy and tolerating it well for at least 1 month. For individuals with established ASCVD or multiple ASCVD risk factors, initiation of other lipid lowering therapy prior to participation in DESIFOR is encouraged.
• 2. At least 30 days since discontinued use of a statin

Exclusion Criteria:

• Women who are pregnant, nursing or attempting to become pregnant
• Individuals who experienced severe reactions in the past, including rhabdomyolysis, severe myositis, anaphylaxis
• Individuals who are not otherwise clinically indicated to take rosuvastatin 20 mg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Placebo taken first, drug taken second; The placebo is assigned to the patient first, with the medication taken in the second part of participation.	Drug: Rosuvastatin (Crestor); The patient will take 3 28-day packs of placebo and 2 28-day packs of rosuvastatin. The order in which they take the placebo or rosuvastatin will be assigned at random.; Drug: Placebo; The patient will take 3 28-day packs of placebo and 2 28-day packs of rosuvastatin. The order in which they take the placebo or rosuvastatin will be assigned at random.
Other: Drug taken first, then placebo taken second; The placebo is assigned to the patient first, with the medication taken in the second part of participation.	Drug: Rosuvastatin (Crestor); The patient will take 3 28-day packs of placebo and 2 28-day packs of rosuvastatin. The order in which they take the placebo or rosuvastatin will be assigned at random.; Drug: Placebo; The patient will take 3 28-day packs of placebo and 2 28-day packs of rosuvastatin. The order in which they take the placebo or rosuvastatin will be assigned at random.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Musculoskeletal symptom presence/absence	To determine the prevalence of true statin intolerance, defined by a statistical difference in the mean musculoskeletal symptom score while on statin therapy compared to placebo, in patients previously identified as statin intolerant.	9 months
Statin Tolerance	To determine the prevalence of statin tolerance, defined as continuous use of 3 months of unblinded rosuvastatin, in individuals with previous statin intolerance but without evidence of true statin intolerance in the DESIFOR protocol.	9 months
Variables associated with statin intolerance	To determine the clinical variables associated with true statin intolerance.	9 months

Collaborators and Investigators

• Sponsor: Minneapolis Heart Institute Foundation

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: January 23, 2025
• First Submitted That Met QC Criteria: January 28, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 28, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: LDL; LDL Cholesterol; Statin Intolerance; lipid-lowering medication
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: 2236054

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No