The Effect of Roxadustat on the Levels of Renal Oxygenation in Patients With Diabetes Nephropathy (FOXTROT)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in kidney oxygenation levels
研究概览
简要总结
The study will investigate if treatment with Roxadustat improves kidney oxygenation in diabetic patients with nephropathy receiving treatment for renal anemia, compared to patients receiving treatment with darbepoetin alpha.
Participants will be randomized to either treatment, and receive equal care for renal anemia. Kidney oxygenation will be examined before treatment start and after 24 weeks using BOLD-MRI (blood oxygen level-defendant MRI), a non-invasive method available for measurement of tissue oxygenation levels that is comparable with direct invasive measurement of partial oxygen pressure. Blood and urin samples will be collected in connection to these visits. The primary endpoint is the change in medullary and cortical R2* (inversely proportional to the tissue oxygenation content) after 24 weeks. Secondary endpoints will be albuminuria and urinary levels of ROS (evaluated by electron paramagnetic resonance (EPR) spectroscopy with CPH spin probes).
详细描述
Aims
The general aim of this study is to investigate the effects of systemic administration of Evrenzo (Roxadustat [RD]) or Aranesp (darbepoetin alpha [DA]) on the levels of renal oxygenation in patients with diabetic nephropathy and associated anemia.
The investigation will elucidate if RD, a prolyl-hydroxylase (PHD) inhibitor and subsequent Hypoxia-Inducible Factor 1 (HIF) activator, can reduce renal hypoxia, compared to DA, which lacks effects on HIF.
Background
Diabetes complications represent a huge health problem and concern for modern diabetes therapy, with dramatic consequences for the affected individuals and society.
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
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diabetes mellitus with anemia caused by DKD, and indication for treatment with erythropoetin/erythropoietin-stimulating drugs.
- •Diabetes duration 10+ years.
- •Chronic kidney disease (CKD) stage 3-4
- •Symptomatic anemia with Hb <10g/dl
- •Contraception: Female subjects must be postmenopausal, surgically sterile, or if premenopausal (and not surgically sterile), be prepared to use ≥1 effective method of contraception during the study and for 30 days after the last visit. Effective methods of contraception are those listed below:
- •Double barrier method, i.e. (a) condom (male or female) or (b) diaphragm, with spermicide; or
- •Intrauterine device; or
- •Vasectomy (partner); or
- •Hormonal (e.g., contraceptive pill, patch, intramuscular implant, or injection); or
- •Abstinence, if in line with the preferred and usual lifestyle of the subject.
- •Signed informed consent.
排除标准
- •Anemia not related to CKD.
- •Dialysis dependent CKD
- •Currently treated for renal anemia using erythropoietin-stimulating drugs
- •Infections during the last 30 days.
- •Severe hypertension (≥180mmHg systolic or >110mmHg diastolic blood pressure)
- •Liver failure (Child-Pugh class B-C)
- •History of epilepsy or seizures
- •Any concomitant disease or condition that may interfere with the possibility for the patient to comply with or complete the study protocol.
- •Ongoing drug or alcohol abuse.
- •Known allergy to RD or DA
- •Severe claustrophobia
- •Participation in another ongoing pharmacological study
- •If female: plans to become pregnant, known pregnancy or a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or currently breastfeeding.
- •Unwillingness to participate following oral and written information
- •Other severe acute or chronic medical or psychiatric condition that makes the subject inappropriate for the study, as judged by the investigator.
- •History of thrombosis (DVT, pulmonary embolism)
研究组 & 干预措施
Roxadustat
The group will receive Roxadustat (Evrenzo) three times weekly at an initial dose of 70mg (for body weight <100.0 kg) or 100 mg (for body weight weight ≥100.0 kg). The dosage for both arms will be adjusted to keep Hb at the recommended levels between 11-12g/dl.
干预措施: Roxadustat (Drug)
Darbepoietin alpha
The control group will receive darbepoietin alpha (Aranesp) s.c. 0.45mg/kg once a week. The dosage for both arms will be adjusted to keep Hb at the recommended levels between 11-12g/dl.
干预措施: Darbepoietin Alfa (Drug)
结局指标
主要结局
Change in kidney oxygenation levels
时间窗: 24 Weeks
Kidney oxygenation will be evaluated using BOLD-MRI prior to start of therapy, and once again after 24 weeks of treatment with either RD or DA. Primary endpoint is the change in medullary and cortical R2\* (inversely proportional to the tissue oxygenation content) after 24 weeks.
次要结局
- Change in albuminuria(24 Weeks)
- Change in urinary reactive oxygen species (ROS)(24 Weeks)