Efficacy of Lower Dose Prednisolone in the Induction of Remission of Lupus Nephritis
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Number of participants achieving complete renal remission
研究概览
简要总结
The LN is a common cause of mortality and morbidity in SLE. The use of high-dose glucocorticoids (GC) with an immunosuppressive agent is usual practice for treating this condition. Higher dose of GC use might cause adverse effects along with clinical improvement. Studies had reported comparable outcome of lower dose of GC with minimum side effects. The aim of this study was to determine the outcome of lower dose prednisolone in the induction of remission of proliferative LN.
This prospective, clinical trial was conducted in Rheumatology outpatient and inpatient department of BSMMU from July 2018 to September 2019. Thirty-two subjects were enrolled after having informed consent. The ACR (American College of Rheumatology) criteria was followed for diagnosis of SLE. The patients of both genders, age ≥18 years, who fulfilled the ACR criteria of LN and unable to afford MMF were enrolled.
The patient evaluation tool was SELENA-DAI and Bengali version of SF-12 questionnaire. The 24-hour urinary protein, urine R/M/E, serum creatinine, CBC, serum C3, C4 levels and anti-dsDNA were done at baseline and at final visit of the study.
All patients received pulse I/V methylprednisolone 500 mg/day daily for 3 doses. After then experimental group received oral prednisolone 0.5 mg/kg/day and control group received oral prednisolone 1 mg/kg/day for a period of 4 weeks. After then the prednisolone was tapered by 10 mg/day in every two weeks until 40 mg/day, then 5 mg/day in every two weeks until 10 mg/day is reached, after two weeks the dose was tapered by 2.5 mg/day to a maintenance dose of 7.5 mg/day. Both groups were treated in the background of hydroxychloroquine (HCQ), angiotensin receptor blocker (ARB) and pulse I/V cyclophosphamide (CYC) for 6 cycle.
The ethical clearance was obtained from Institutional Review Board (IRB) of BSMMU and technical clearance was taken from rheumatology technical board.
详细描述
Rationale:
Lupus nephritis (LN) is a very common complication of systemic lupus erythematosus (SLE). Currently available all guidelines suggest an induction phase with glucocorticoids along with another immunosuppressive agent. However, the basis of using high dose of glucocorticoids are mostly empirical. There is no published data comparing low and high dose glucocorticoids in the treatment of LN. Use of high dose of glucocorticoids may increase morbidity like osteopenia, osteonecrosis of neck of femur, Cushing syndrome etc. Moreover, rate of infectious disease is very high in the investigator's country. Patient treated with high dose glucocorticoids may prone to develop serious infectious conditions. Researchers are currently trying to develop new regimen, which can replace the use of long-term glucocorticoids to treat LN. Unless the alternative regimen developed, well-controlled study is necessary to establish a lowest possible dose of glucocorticoid to treat this condition.
Research question:
Is lower dose prednisolone similar efficacious as the higher dose regimen in achieving complete remission of proliferative lupus nephritis?
Null hypothesis:
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years of both sexes
- •Diagnosed case of systemic lupus erythematosus (SLE) as per ACR criteria
- •Patients consenting to participate in the study
- •Class III/IV lupus nephritis (LN) as evidenced by:
- •Confirmed proteinuria ≥ 500 mg/24 hours when assessed by 24-hour urine collection And
- •High titer anti-dsDNA (>75 U/ml) and low C3 (<0.9 g/l) and/or C4 (<0.1 g/l) Or
- •Kidney biopsy: with a histologic diagnosis of class III or IV lupus nephritis (International Society of Nephrology/Renal Pathology Society 2003 classification of lupus nephritis)
排除标准
- •Subjects not giving written informed consent
- •Pregnant or lactating women
- •Patient willing to be treated with MMF rather than CYC
- •Had taken CYC within 4 weeks prior to screening
- •Had taken >15 mg/day of prednisolone (or equivalent) for a period of >10 days during the previous month
- •Renal thrombotic microangiopathy
- •Estimated glomerular filtration rate (eGFR) as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation of ≤45 mL/min/1.73 m2 at screening
- •Dialysis dependent patients, currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period
- •A previous kidney transplant or planned transplant within study treatment period
- •Altered liver function (alanine aminotransferase greater than 2.5 times the upper limit of normal) at screening and confirmed before randomization
- •Lymphoproliferative disease or previous total lymphoid irradiation
- •Active bleeding disorders
- •Active tuberculosis (TB)
- •Diabetes mellitus
- •Any known hypersensitivity or contraindication to CYC, corticosteroids or any components of these drug products
- •Any overlapping autoimmune condition for which the condition or the treatment of the condition may affect the study assessments or outcomes (e.g., scleroderma with significant pulmonary hypertension; any condition for which additional immunosuppression is indicated)
研究组 & 干预措施
Low dose group
Prednisolone 0.5 mg/kg/day
干预措施: Prednisolone (Drug)
High dose group
Prednisolone 1 mg/kg/day
干预措施: Prednisolone (Drug)
结局指标
主要结局
Number of participants achieving complete renal remission
时间窗: At the end of 24th week
Complete renal remission is defined as a decline in the UTP level to \<500 mg/day and return of serum creatinine to previous baseline.
次要结局
- Number of participants achieving partial renal remission(At the end of 24th week)
研究者
Dr. Iftekhar Hussain Bandhan
Principal Investigator
Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh