Efficacy and Safety of Simvastatin-ezetimibe Combination Therapy Among Patients With SLE

Early Phase 1

• Conditions: Atherosclerosis
• Interventions: Drug: Ezetimibe+Simvastatin Drug Combination

• Registration Number: NCT02548936
• Lead Sponsor: Peking Union Medical College Hospital

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.

Study Timeline

• Study Start: 2015-04
• Status Verified: 2015-08
• Study First Submitted: 2015-08-31
• Study First Submitted QC: 2015-09-11
• Last Update Submitted: 2015-09-11
• Study First Posted: 2015-09-14
• Last Update Posted: 2015-09-14
• Primary Completion: 2016-10
• Study Completion: 2016-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lipid-lowering treatment	Ezetimibe+Simvastatin Drug Combination	The Lipid-lowering treatment is Ezetimibe+Simvastatin Drug Combination by oral administration. The patients in intervention group received simvastatin (10mg/day) + ezetimibe (20 mg/day) combined therapy for 12 month.

Primary Outcome Measures

Name	Time	Method
The change of carotid intima media thickness over 12 months	baseline, 12 months	CIMT(Unit: millimeter) is defined as the distance between the lumen-intima interface and the media-adventitia interface, which corresponded to the inner and outer echogenic lines seen on the B-mode ultrasound image.

Secondary Outcome Measures

Name	Time	Method
The rate of abnormal elevated alanine aminotransferase (ALT)	1 month	ALT \>40U/L
The rate of abnormal elevated alanine aminotransferase	12 months	ALT \>40U/L
The rate of abnormal elevated creatine kinase (CK)	1 month	CK \>60U/L
The rate of abnormal elevated creatine kinase	12 month	CK \>60U/L

Trial Locations

Locations (1)

Peking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China