Can Simvastatin Significantly Reduce the Amount of Immunosuppressive Medication Required by Patients With Sight Threatening Uveitis? A Phase 2b, Single Site, Randomized, Placebo Controlled, Double Blinded Trial.
试验速览
- 阶段
- 2 期
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- 1. Change in dose (mg) of prednisolone after 12 months of treatment
研究概览
简要总结
The trial will compare the effect on disease control and immunosuppression treatment of adding simvastatin 80mg once daily, over a follow-up and treatment period of 2 years. Patients will be randomised in a 1:1 fashion to standard treatment with placebo or standard treatment with the addition of simvastatin (80mg daily). They will be followed at 3 months intervals for 2 years with a primary end point of mean reduction in corticosteroid dosage at the 12 month follow-up visit.
详细描述
This is a non-commercial trial to explore the effect of simvastatin 80mg od on the dose of corticosteroids and immunosuppression in patients with sight-threatening uveitis.
In order to detect a clinical effect the study is designed as a double blinded, parallel group, placebo-controlled, randomised trial. Double blinding will be achieved through the use of a placebo as well as a masked clinical assessor.
Based on the reported effect of simvastatin on brain atrophy among multi[le sclerosis patients after 12 months treatment, patients will receive treatment or placebo and will be treated and followed up for 24 months.
Patients randomised to simvastatin will receive a dose of 80mg od. There will be no dose escalation.
Patients will be reviewed every 3 months and will undergo a complete ophthalmic examination with treatment adjustment accordingly.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be >18 years and under 80 years.
- •Both sexes may participate, but, because of possible teratogenicity of simvastatin women may do so only following counselling about the need for adequate contraception.
- •Women of child bearing potential will have to have a negative pregnancy test prior to enrolment.
- •Patients must have been previously diagnosed with intermediate, posterior or panuveitis (as defined by the standardization of uveitis nomenclature group).14
- •Patients must be taking systemic prednisolone 10mg once daily or more.
- •Patients may be treated with or without a second line agent.
- •Patients must be willing and able to provide informed consent
排除标准
- •No associated underlying systemic disease causing the uveitis.
- •Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 6 weeks after treatment discontinuation.
- •Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for trial treatment.
- •Females must not be breastfeeding.
- •Patients concomitantly taking ciclosporin, fibrates, amiodarone, amlodipine, verapamil, cytochrome P450 3A4 inhibitors (e.g. itraconazole, ketoconazole, posaconazole, voriconazole), HIV protease inhibitors (e.g. nelfinavir), erythromycin, clarithromycin, telithromycin, nefazodone, gemfibrozil, danazol, fusidic acid, diltiazem or anti-coagulants.
- •Patients will be advised not to drink grapefruit juice during the study.
- •Family history of hereditary muscle disorders.
- •Active Liver disease
- •Severe renal insufficiency.
- •Persistently elevated serum transaminases.
- •Allergies to excipients of simvastatin and placebo
- •Lactose intolerance
- •Involvement in other clinical trials
研究组 & 干预措施
Simvastatine
Group of patients receiving simvastatin 80mg once daily in addition to standard care
干预措施: Simvastatin (Drug)
Placebo
Group of patients receiving placebo once daily in addition to standard care
干预措施: Placebo (Drug)
结局指标
主要结局
1. Change in dose (mg) of prednisolone after 12 months of treatment
时间窗: 12 months
To determine whether the mean reduction in prednisolone dosage achieved at 12 months is greater in the simvastatin group compared to the placebo treated group?
次要结局
- The number of disease relapses by 24 months(24 months)
- Blood cholesterol and lipid levels at 24 months as compared to baseline(24 months)
- The mean reduction in prednisolone achieved at 24 months.(24 months)
- The chnage in the number of 2nd-line immunosuppressive drugs at 24 months(24 months)
- Change in visual acuity at 12 and 24 months as compared to baseline(12 and 24 months)
- Treg and Th17 levels at 12 and 24 months as compared to baseline(12 and 24 months)
- Number of patients with adverse events.(24 months)
- The change in dose (mg) of 2nd-line immunosuppressive drugs at 24months(24 months)