Clinical trial NCT02548936: Efficacy and Safety of Simvastatin-ezetimibe Combination Therapy Among Patients With SLE
Official title: Efficacy and Safety of Simvastatin-ezetimibe Combination Therapy in Reduction of Progression of Atherosclerosis Among Patients With Systemic Lupus Erythematosus: A Randomized Single-Blind Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Atherosclerosis
Keywords: Cholesterol, LDL
Carotid Intima-Media Thickness
Atherosclerosis
Ezetimibe, Simvastatin Drug Combination
Lupus Erythematosus, Systemic
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2015-09-14
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a randomized single-blind trial. This study aimed to determine if intensive lipid-lowering therapy (simvastatin-ezetimibe combination therapy) could reduce the progression of atherosclerosis effectively and safely among SLE patients with carotid artery intima thickening. The study results were expected to be helpful for SLE patients in preventing atherosclerosis.

Detailed description: Patient Registries: A convenient consecutive sampling was used to recruit participants from outpatients in department of rheumatism of PUMCH. Prior to their enrollment in the study, all patients gave written, informed consent. To minimize subject non-response or rejection, the investigators inform patients the benefits and risks, and feedback them all physical examination results for free in the recruit period.

Randomization: A randomization will be used to allocate patients into Lipid-lowering treatment group and control group.

Blind: A trained ultrasonographer who assessed carotid intima media thickness (CIMT) (at baseline and 12 months) will be blinded to all clinical and treatment information.

Statistical analysis: The characteristics of the study sample were summarized using descriptive statistics with dichotomous or ordinal data presented as percentages and continuous data as means, standard deviations, and medians, interquartile range. Differences of progression rate of atherosclerosis between intervention group and control group were assessed with either the t test or the non-parametric Wilcoxon test. A multivariable linear regression model will be used to evaluate the relationship between the progression of CIMT and intervention after controlling for confounding factors. Statistical significance was defined as a 2-tailed P value less than 0.05. All calculations were performed using SAS version 9.3.

Quality Control and Data Management: Two doctors (not the main investigator) who come from department of cardiology with the experiences of clinical trial and a data manager will be serving as Data and Safety Monitor. A monthly meeting will be set up for investigators and monitors. The monitors need to review the study protocol and set Data Safety Management plan before recruitment. Then, they need to review rates of recruitment, adherence, follow-up conditions and assess the efficacy and harm during the study. If Monitors find that the simvastatin-ezetimibe combination therapy is causing severe adverse event, then a detailed record is needed. Monitors need to inform the main investigator within 3 hours and to inform state China Food and Drug Administration within 24 hours. Interim monitoring will focus on data quality, percentage of AE or SAE, and evidence of benefit.

Eligibility criteria: Inclusion Criteria:

1. age ≥18 years and clinical diagnosis of SLE
2. abnormal CIMT (≥0.9 mm at any site) by B-mode ultrasound
3. LDL-C≥100mg/dl
4. a signed written informed consent was able to be obtained.

Exclusion Criteria:

1. atherosclerotic cardiovascular disease
2. diabetes
3. history of intolerance or allergy to the statins or ezetimibe
4. had ever received statins or ezetimibe within 12 months of study entry
5. LDL-C≥190mg/dl
6. active infection
7. ALT was higher than 2 times of the upper normal limit or CK was higher than 1.5 times of the upper normal limit.
8. pregnant or lactating women
9. patients with severe SLE.

Primary outcomes:
measure: The change of carotid intima media thickness over 12 months
timeFrame: baseline, 12 months
Secondary outcomes:
measure: The rate of abnormal elevated alanine aminotransferase (ALT)
timeFrame: 1 month
measure: The rate of abnormal elevated alanine aminotransferase
timeFrame: 3 months
measure: The rate of abnormal elevated alanine aminotransferase
timeFrame: 6 months
measure: The rate of abnormal elevated alanine aminotransferase
timeFrame: 12 months
measure: The rate of abnormal elevated creatine kinase (CK)
timeFrame: 1 month
measure: The rate of abnormal elevated creatine kinase
timeFrame: 3 month
measure: The rate of abnormal elevated creatine kinase
timeFrame: 6 month
measure: The rate of abnormal elevated creatine kinase
timeFrame: 12 month
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Shuyang Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References: