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

Atherosclerosis Clinical Trial

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02548936
• Other study ID #: pumch-sleas
• Status: Enrolling by invitation
• Phase: Phase 0
• First received: August 31, 2015
• Last updated: September 11, 2015
• Start date: April 2015
• Est. completion date: December 2016

Study information

• Verified date: August 2015
• Source: Peking Union Medical College Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: National Health and Family Planning Commission
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 30
• Est. completion date: December 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Atherosclerosis

Intervention

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.

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	The rate of abnormal elevated alanine aminotransferase (ALT)	ALT >40U/L	1 month	Yes
Secondary	The rate of abnormal elevated alanine aminotransferase	ALT >40U/L	3 months	Yes
Secondary	The rate of abnormal elevated alanine aminotransferase	ALT >40U/L	6 months	Yes
Secondary	The rate of abnormal elevated alanine aminotransferase	ALT >40U/L	12 months	Yes
Secondary	The rate of abnormal elevated creatine kinase (CK)	CK >60U/L	1 month	Yes
Secondary	The rate of abnormal elevated creatine kinase	CK >60U/L	3 month	Yes
Secondary	The rate of abnormal elevated creatine kinase	CK >60U/L	6 month	Yes
Secondary	The rate of abnormal elevated creatine kinase	CK >60U/L	12 month	Yes