Efficacy of Lower Dose Prednisolone in the Induction of Remission of Lupus Nephritis

NCT04146220 | Completed Phase 4 DMC

• 1 other identifier: BSMMU/2018/8050
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lupus Nephritis

Outcome Measures

Primary Outcomes (1)

• Number of participants achieving complete renal remission

  Complete renal remission is defined as a decline in the UTP level to \<500 mg/day and return of serum creatinine to previous baseline.

  At the end of 24th week

Secondary Outcomes (1)

• Number of participants achieving partial renal remission

  At the end of 24th week

Other Outcomes (4)

• Rate of achievement of normal anti-dsDNA level

  At the end of 24th week

• Rate of achievement of normal complements level

  At the end of 24th week

• Rate of reduction of Safety of Estrogens in Systemic Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index score

  At the end of 24th week

Study Arms (2)

Low dose group

EXPERIMENTAL

Prednisolone 0.5 mg/kg/day

Drug: Prednisolone

High dose group

ACTIVE COMPARATOR

Prednisolone 1 mg/kg/day

Drug: Prednisolone

Interventions

Prednisolone DRUG

Patients of the low and the high dose groups recieved prednisolone in different dose for initial 4 weeks, then tapered gradually. Both groups received pulse I/V methylprednisolone 500 mg/day daily for initial 3 days and monthly cyclophosphamide infusion 750-1000 mg/m2 body surface area.

Also known as: Pred

High dose group; Low dose group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• Malignancy
• Lymphoproliferative disease or previous total lymphoid irradiation
• Active bleeding disorders
• Active tuberculosis (TB)
• Diabetes mellitus

Sponsors & Collaborators

• Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh: lead

Study Sites (1)

Bangabandhu Sheikh Mujib Medical University

Dhaka, 1217, Bangladesh

Location

Related Publications (16)

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  PMID: 22556106 BACKGROUND

• Almaani S, Meara A, Rovin BH. Update on Lupus Nephritis. Clin J Am Soc Nephrol. 2017 May 8;12(5):825-835. doi: 10.2215/CJN.05780616. Epub 2016 Nov 7.

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  PMID: 22271756 BACKGROUND

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  PMID: 3511372 RESULT

• Boumpas DT, Austin HA 3rd, Vaughn EM, Klippel JH, Steinberg AD, Yarboro CH, Balow JE. Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet. 1992 Sep 26;340(8822):741-5. doi: 10.1016/0140-6736(92)92292-n.

  PMID: 1356175 RESULT

• Gourley MF, Austin HA 3rd, Scott D, Yarboro CH, Vaughan EM, Muir J, Boumpas DT, Klippel JH, Balow JE, Steinberg AD. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med. 1996 Oct 1;125(7):549-57. doi: 10.7326/0003-4819-125-7-199610010-00003.

  PMID: 8815753 RESULT

• Illei GG, Austin HA, Crane M, Collins L, Gourley MF, Yarboro CH, Vaughan EM, Kuroiwa T, Danning CL, Steinberg AD, Klippel JH, Balow JE, Boumpas DT. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med. 2001 Aug 21;135(4):248-57. doi: 10.7326/0003-4819-135-4-200108210-00009.

  PMID: 11511139 RESULT

• Houssiau FA, Vasconcelos C, D'Cruz D, Sebastiani GD, Garrido Ed Ede R, Danieli MG, Abramovicz D, Blockmans D, Mathieu A, Direskeneli H, Galeazzi M, Gul A, Levy Y, Petera P, Popovic R, Petrovic R, Sinico RA, Cattaneo R, Font J, Depresseux G, Cosyns JP, Cervera R. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum. 2002 Aug;46(8):2121-31. doi: 10.1002/art.10461.

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• Mehra S, Usdadiya JB, Jain VK, Misra DP, Negi VS. Comparing the efficacy of low-dose vs high-dose cyclophosphamide regimen as induction therapy in the treatment of proliferative lupus nephritis: a single center study. Rheumatol Int. 2018 Apr;38(4):557-568. doi: 10.1007/s00296-018-3995-3. Epub 2018 Feb 15.

  PMID: 29450636 RESULT

• Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne D, Li LS, Mysler E, Sanchez-Guerrero J, Solomons N, Wofsy D; Aspreva Lupus Management Study Group. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009 May;20(5):1103-12. doi: 10.1681/ASN.2008101028. Epub 2009 Apr 15.

  PMID: 19369404 RESULT

• Sahay M, Saivani Y, Ismal K, Vali PS. Mycophenolate versus Cyclophosphamide for Lupus Nephritis. Indian J Nephrol. 2018 Jan-Feb;28(1):35-40. doi: 10.4103/ijn.IJN_2_16.

  PMID: 29515299 RESULT

MeSH Terms

Conditions

Lupus Nephritis

Interventions

Prednisolone; prednylidene

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Prof. Nazrul Islam, FCPS, MD

  Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 29, 2019
• First Posted: October 31, 2019
• Study Start: July 16, 2018
• Primary Completion: September 30, 2019
• Study Completion: September 30, 2019
• Last Updated: October 31, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)