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

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

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.

Study Overview

• Status: Unknown
• Conditions: Atherosclerosis
• Intervention / Treatment: Drug: Ezetimibe+Simvastatin Drug Combination

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lipid-lowering treatment; 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.	Drug: Ezetimibe+Simvastatin Drug Combination; The patients in Ezetimibe+Simvastatin Drug Combination group received simvastatin (10mg/day) + ezetimibe (20 mg/day) by oral administration for 12 month.; Other Names: ezetimibe/simvastatin
No Intervention: No lipid-lowering treatment; Without any Lipid-lowering treatment for 12 month.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change of carotid intima media thickness over 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.	baseline, 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of abnormal elevated alanine aminotransferase (ALT)	ALT >40U/L	1 month
The rate of abnormal elevated alanine aminotransferase	ALT >40U/L	3 months
The rate of abnormal elevated alanine aminotransferase	ALT >40U/L	6 months
The rate of abnormal elevated alanine aminotransferase	ALT >40U/L	12 months
The rate of abnormal elevated creatine kinase (CK)	CK >60U/L	1 month
The rate of abnormal elevated creatine kinase	CK >60U/L	3 month
The rate of abnormal elevated creatine kinase	CK >60U/L	6 month
The rate of abnormal elevated creatine kinase	CK >60U/L	12 month

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Shuyang Zhang, MD, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Anticipated): October 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: August 31, 2015
• First Submitted That Met QC Criteria: September 11, 2015
• First Posted (Estimate): September 14, 2015

Study Record Updates

• Last Update Posted (Estimate): September 14, 2015
• Last Update Submitted That Met QC Criteria: September 11, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Atherosclerosis; Lupus Erythematosus, Systemic; Carotid Intima-Media Thickness; Cholesterol, LDL; Ezetimibe, Simvastatin Drug Combination
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin; Ezetimibe; Ezetimibe, Simvastatin Drug Combination
• Other Study ID Numbers: pumch-sleas