NCT02503735终止不适用
Effect of Ledipasvir and Sofosbuvir on Proteinuria and Estimated Glomerular Filtration Rate in Patients With Early Stage (1-3) Hepatitis C Associated Chronic Kidney Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- The Percent Change in Proteinuria
研究概览
简要总结
Treatment protocol to see if people with hepatitis C (HCV) and chronic kidney disease (CKD) who are treated with Harvoni for 12 weeks have improvements in their kidney disease.
详细描述
The investigators hypothesize that patients with early stage (1-3) CKD caused by HCV infection will have significantly improved proteinuria and eGFR after viral eradication with 12 weeks of treatment Harvoni (LDV/SOF). This trial data will serve as the basis to support further study of LDV/SOF in patients with early CKD. Slowing progression of CKD is a critical goal, as the increasing incidence and prevalence of advanced CKD and end stage renal disease (ESRD) places significant health burden on patients and tremendous costs on our health-care system.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject has signed the written informed consent
- •Male or female ≥ 18 year of age
- •HCV genotype 1 or 4 with ribonucleic acid (HCV RNA) greater than 1000 international units (IU)/milliliter (mL), determined by HCV RNA polymerase chain reaction Roche TaqMan quantitative assay.
- •Initial diagnosis of proteinuric chronic kidney disease occurred < 7 years prior to completion of screening
- •Women of childbearing potential (i.e. women who have not undergone hysterectomy or bilateral oophorectomy, or no medically documented ovarian failure, and are ≤ 50 years of age) must agree to 1 medically approved contraceptive measures and have their partners agree to an additional barrier method of contraception for the duration of the study and for 4 weeks after the last administration of the study drug. Women of childbearing potential must not rely on hormone-containing contraceptive as a form of birth control during the study but may use. An intrauterine device, female barrier methods with cervical cap or diaphragm with spermicidal agent, tubal sterilization, or vasectomy in male partners.
- •Male subjects must agree to consistently and correctly use a condom during heterosexual intercourse and avoid sperm donation for the duration of this study and for 90 days after the last dose of ledipasvir and sofosbuvir. Additionally, if their female partner is of childbearing potential (as defined above), their partner must agree to use either 1 of the non-hormonal methods of birth control listed above or a hormone-containing contraceptive for 90 days after last study drug date. Hormone-containing contraceptive options for partners include implants of levonorgestrel, injectable progesterone, oral contraceptives, contraceptive vaginal ring, or transdermal contraceptive pat
- •Adequate organ function defined as follows platelets ≥ 50 x 109/L; hemoglobin ≥ 9 g/dL, estimated glomerular filtration rate ≥ 30mL/min/1.73m2 as estimated by CKD-Epi equation.
- •Liver imaging to exclude hepatocellular carcinoma (HCC) is required within 6 months in any patient with cirrhosis.
- •Has > 300mg/g creatinine proteinuria on two urine samples obtained within 30 days of starting ledipasvir and sofosbuvir.
排除标准
- •History of evidence of clinically significant disorder other than hepatitis C virus infection or clinically significant laboratory finding that in the investigator's judgment would pose a risk to subject safety, interfere with study procedures, or prevent completion of the study.
- •Pregnant or lactating female
- •Uncontrolled depression or psychiatric disease interfering with the ability to comply with the study procedures or complete the study
- •History or presence of any form of cancer within 3 years prior to enrollment, with the exception of excised basal cell or squamous cell carcinoma of the skin, stage 0 or 1 melanoma, or cervical carcinoma in site or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis.
- •Experience life-threatening cryoglobulinemic vasculitis requiring initiation of rituximab, steroids or plasmapheresis.
- •Concomitant use of cimetidine, trimethoprim or other drugs which can increase tubular creatinine reabsorption
- •Uncontrolled cardiovascular or pulmonary disease
- •Uncontrolled hypertension
- •Known HIV infection
- •Known hypersensitivity to ledipasvir or sofosbuvir
- •Prior HCV treatment failure using a medication in the NS5A inhibitor class
- •Individuals who are taking the following medications and require continuation of the medications during the proposed study period will be excluded, given known interactions with ledipasvir-sofosbuvir: Carbamazepine, phenytoin, phenobarbital, oxcarbazepine, rifabutin, rifampin, isoniazid, rifapentine, rosuvastatin, proton pump inhibitors, digoxin, modafinil, and St. John's wort, milk thistle, Echinacea.
- •Having an alternate explanation of chronic kidney disease, including:
- •Diabetic kidney disease, either by biopsy findings or duration of uncontrolled diabetes > 8 years without serologic evidence of immune-complex related kidney disease
- •Chronic hypertensive nephropathy without proteinuria
- •Lupus nephritis
- •Multiple myeloma
- •Obesity related proteinuria, BMI > 35
- •Ongoing nephrotoxic medication use, including NSAIDS
- •Polycystic kidney disease
- •Kidney biopsy showing an alternate explanation for chronic kidney disease
研究组 & 干预措施
12 weeks treatment with Sofosbuvir/Ledipasvir (400mg/90mg)
Other
10 patients with hepatitis C (HCV) and HCV-associated CKD that will receive 12 weeks treatment with Sofosbuvir/Ledipasvir (400mg/90mg)
干预措施: Sofosbuvir/Ledipasvir FDC (Drug)
结局指标
主要结局
The Percent Change in Proteinuria
时间窗: Baseline and 24 weeks (12 weeks after completion of Harvoni)
% change in proteinuria from baseline (timepoint week 0) through timepoint week 24, which was 12 weeks after completion of Harvoni.
次要结局
- Median Change in eGFR From Baseline to Timepoint Week 24(24 weeks)
- Number of Participants With ≥25% Reduction in Proteinuria(24 weeks)
- Mean Time in Weeks to Maximum Reduction in Proteinuria(52 weeks)
- Median Change in eGFR From Baseline to Timepoint Week 52(52 weeks)
- Change in Urinary β-2microglobulin Levels Before Therapy(24 weeks)
- Change in Urinary β-2microglobulin Levels After Therapy(24 weeks)
研究者
Raymond Chung
Director of Hepatology
Massachusetts General Hospital
研究点 (1)
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