Lupus NephritisPhase 4LNNCT04146220
Efficacy of Lower Dose Prednisolone in the Induction of Remission of Lupus Nephritis
A Phase 4 study testing Prednisolone in people with Lupus Nephritis, run by Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh at 1 site in Bangladesh.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lupus Nephritis
- What is being tested?
- Prednisolone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteBangladesh
- Study dates
- 16 Jul 2018to 30 Sep 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 17Show fewer
- 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
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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.
Read the detailed description
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:
Lower dose prednisolone regimen is inferior to the higher dose regimen by more than - Δ in achieving the complete remission of proliferative lupus nephritis.
H0: P1-P2 ≤ - Δ P1 = Test drug (Prednisolone 0.5 mg/kg/day) P2 = Control drug (Prednisolone 1 mg/kg/day) Δ = Non-inferiority margin
Alternative hypothesis:
Lower dose prednisolone regimen is inferior to the higher dose regimen by less than - Δ in achieving the complete remission of proliferative lupus nephritis.
H1: P1-P2 > - Δ
General objective:
To assess efficacy of prednisolone 0.5 mg/kg/day in achieving remission of proliferative LN compared to 1 mg/kg/day
Specific objectives:
To compare:
- Changes of UTP level from the baseline to 24 weeks
- Changes of active urinary sediments level from the baseline to 24 weeks
- Changes of serum creatinine level from the baseline to 24 weeks
- Changes of quality of life from the baseline to 24 weeks
- Adverse effects during study period
Primary endpoint: (Time frame: at the end of 24th week)
- Complete renal remission
Secondary endpoints: (Time frame: at the end of 24th week)
- Renal remission (complete/partial) at 24 weeks
- Changes of UTP level from the baseline at 24 weeks
- Proportion of subjects with active urinary sediment at 24 weeks
- Changes of serum creatinine level from the baseline at 24 weeks
- Changes of eGFR from the baseline at 24 weeks
- Changes of anti-dsDNA level from the baseline at 24 weeks
- Changes of complements (C3 and C4) level from the baseline at 24 weeks
- Changes of SELENA-SLEDAI score from the baseline at 24 weeks
- Changes of SF-12 score from the baseline at 24 weeks
Study procedure:
This open labeled randomized controlled clinical trial was conducted in the outpatient and the inpatient department of Rheumatology, BSMMU from July 2018 to September 2019. Patients of SLE were interviewed after taking verbal consent. They were screened with history, physical examination, urine RME, 24hours UTP reports. Patients fulfilling the inclusion and exclusion criteria were enrolled in the study after taking informed written consent. Total 32 patients of SLE with proliferative LN were enrolled in the study. After the enrollment study subjects were randomized into experimental group (low dose group) and control group (high dose group) by lottery. Baseline laboratory tests were urine R/M/E, 24 hours UTP, serum creatinine, anti-dsDNA, C3, C4, CBC with ESR, SGPT. Baseline quality of life was assessed by Bengali version SF-12 questionnaire.
Both groups received pulse I/V methylprednisolone 500 mg/day daily for 3 doses. Then, patients of the low dose group received oral prednisolone 0.5 mg/kg/day (maximum 30 mg/day) and high dose group received oral prednisolone 1 mg/kg/day (maximum 60 mg/day) for initial 4 weeks. In the low dose group, prednisolone was tapered by 5 mg/day in every two weeks until 10 mg/day was reached, then after two weeks the dose was tapered by 2.5 mg/day to a maintenance dose of 7.5 mg/day. In the high dose group, prednisolone was tapered by 10 mg/day in every two weeks until 40 mg, then 5 mg/day in every two weeks until 10 mg/day is reached, after two weeks it was tapered by 2.5 mg/day to a maintenance dose of 7.5 mg/day.
Patients of both groups were treated with monthly CYC infusion, first dose 750 mg/m2 body surface area, subsequent doses were adjusted based on leukocyte nadir (≥ 4000 cells/mm3, doses were increased by 25%, to a maximum of 1 gm/m2 body surface area, the dose were reduced by 25% for leukocyte counts <4000 cells/mm3). Both groups of patients received hydroxychloroquine (HCQ), angiotensin receptor blocker (ARB) and other relevant medications. Patient education, vaccinations against influenza and pneumococcus were given to all the enrolled subjects. All patients were given Pneumocystis jirovecii prophylaxes.
Primary endpoint (complete remission) was assessed at the end of 24th week. Urine R/M/E, CBC with ESR, SGPT and serum creatinine were done in every 4 weeks. Twenty-four hours UTP were done at the end of 12 weeks and 24 weeks. Anti-dsDNA, C3 and C4 were done at the end of 24 weeks. Data were collected from a set of written questionnaires which was supplied to the patients and from physical examination and investigation findings. Quality of life was assessed by Bengali version of SF-12 questionnaire.
- Conditions
- Lupus Nephritis
- Being tested
- Prednisolone
- Medical subject headings
- Lupus Nephritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrednisoloneDrug
Also called Pred
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.
| Study group | Role | What they receive |
|---|---|---|
| Low dose group | Experimental | Prednisolone 0.5 mg/kg/day Receives: Drug: Prednisolone |
| High dose group | Active comparator | Prednisolone 1 mg/kg/day Receives: Drug: Prednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At the end of 24th week
Secondary outcomes (1)
Number of participants achieving partial renal remission
Partial renal remission is defined as stabilization (±25%), or improvement of serum creatinine, but not to normal, and ≥50% decrease in UTP. If there was nephrotic-range proteinuria (UTP>3000 mg/day), improvement requires ≥50% reduction in UTP, and a UTP <3000 mg/day.
Measured: At the end of 24th week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2019
- Study start16 Jul 2018
- Primary completion30 Sep 2019
- Study completion30 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Lupus NephritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Iftekhar Hussain Bandhan, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
- Investigators
- Prof. Nazrul Islam, FCPS, MD, Study chair, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04146220
- Sponsor's protocol ID
- BSMMU/2018/8050
- Acronym
- LN
- Status last verified
- Oct 2019
- First submitted
- 29 Oct 2019
- Last updated
- 31 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, Karpouzas GA, Merrill JT, Wallace DJ, Yazdany J, Ramsey-Goldman R, Singh K, Khalighi M, Choi SI, Gogia M, Kafaja S, Kamgar M, Lau C, Martin WJ, Parikh S, Peng J, Rastogi A, Chen W, Grossman JM; American College of Rheumatology. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken). 2012 Jun;64(6):797-808. doi: 10.1002/acr.21664. No abstract available.
PubMed 22556106Almaani 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.
PubMed 27821390Bertsias GK, Tektonidou M, Amoura Z, Aringer M, Bajema I, Berden JH, Boletis J, Cervera R, Dorner T, Doria A, Ferrario F, Floege J, Houssiau FA, Ioannidis JP, Isenberg DA, Kallenberg CG, Lightstone L, Marks SD, Martini A, Moroni G, Neumann I, Praga M, Schneider M, Starra A, Tesar V, Vasconcelos C, van Vollenhoven RF, Zakharova H, Haubitz M, Gordon C, Jayne D, Boumpas DT; European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association. Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis. 2012 Nov;71(11):1771-82. doi: 10.1136/annrheumdis-2012-201940. Epub 2012 Jul 31.
PubMed 22851469Buttgereit F, Straub RH, Wehling M, Burmester GR. Glucocorticoids in the treatment of rheumatic diseases: an update on the mechanisms of action. Arthritis Rheum. 2004 Nov;50(11):3408-17. doi: 10.1002/art.20583. No abstract available.
PubMed 15529366Seguro LP, Rosario C, Shoenfeld Y. Long-term complications of past glucocorticoid use. Autoimmun Rev. 2013 Mar;12(5):629-32. doi: 10.1016/j.autrev.2012.12.002. Epub 2012 Dec 20.
PubMed 23261815Ruiz-Irastorza G, Danza A, Perales I, Villar I, Garcia M, Delgado S, Khamashta M. Prednisone in lupus nephritis: how much is enough? Autoimmun Rev. 2014 Feb;13(2):206-14. doi: 10.1016/j.autrev.2013.10.013. Epub 2013 Nov 2.
PubMed 24189280Badsha H, Edwards CJ. Intravenous pulses of methylprednisolone for systemic lupus erythematosus. Semin Arthritis Rheum. 2003 Jun;32(6):370-7. doi: 10.1053/sarh.2002.50003.
PubMed 12833245Ruiz-Irastorza G, Danza A, Khamashta M. Glucocorticoid use and abuse in SLE. Rheumatology (Oxford). 2012 Jul;51(7):1145-53. doi: 10.1093/rheumatology/ker410. Epub 2012 Jan 23.
PubMed 22271756Austin HA 3rd, Klippel JH, Balow JE, le Riche NG, Steinberg AD, Plotz PH, Decker JL. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med. 1986 Mar 6;314(10):614-9. doi: 10.1056/NEJM198603063141004.
PubMed 3511372Boumpas 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.
PubMed 1356175Gourley 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.
PubMed 8815753Illei 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.
PubMed 11511139Houssiau 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.
PubMed 12209517Mehra 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.
PubMed 29450636Appel 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.
PubMed 19369404
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Lower Dose Prednisolone in the Induction of Remission of Lupus Nephritis
- ClinicalTrials.gov ID
- NCT04146220
- Acronym / sponsor ID
- LN / BSMMU/2018/8050
- Conditions
- Lupus Nephritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Bangabandhu Sheikh Mujib Medical University, Dhaka, BangladeshUniversity, hospital or other
- Study start
- 16 Jul 2018 (actual)
- Primary completion
- 30 Sep 2019 (actual)
- Study completion
- 30 Sep 2019 (actual)
- First posted
- 31 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
Lower dose prednisolone regimen is inferior to the higher dose regimen by more than - Δ in achieving the complete remission of proliferative lupus nephritis.
H0: P1-P2 ≤ - Δ P1 = Test drug (Prednisolone 0.5 mg/kg/day) P2 = Control drug (Prednisolone 1 mg/kg/day) Δ = Non-inferiority margin
Alternative hypothesis:
Lower dose prednisolone regimen is inferior to the higher dose regimen by less than - Δ in achieving the complete remission of proliferative lupus nephritis.
H1: P1-P2 > - Δ
General objective:
To assess efficacy of prednisolone 0.5 mg/kg/day in achieving remission of proliferative LN compared to 1 mg/kg/day
Specific objectives:
To compare:
- Changes of UTP level from the baseline to 24 weeks
- Changes of active urinary sediments level from the baseline to 24 weeks
- Changes of serum creatinine level from the baseline to 24 weeks
- Changes of quality of life from the baseline to 24 weeks
- Adverse effects during study period
Primary endpoint: (Time frame: at the end of 24th week)
- Complete renal remission
Secondary endpoints: (Time frame: at the end of 24th week)
- Renal remission (complete/partial) at 24 weeks
- Changes of UTP level from the baseline at 24 weeks
- Proportion of subjects with active urinary sediment at 24 weeks
- Changes of serum creatinine level from the baseline at 24 weeks
- Changes of eGFR from the baseline at 24 weeks
- Changes of anti-dsDNA level from the baseline at 24 weeks
- Changes of complements (C3 and C4) level from the baseline at 24 weeks
- Changes of SELENA-SLEDAI score from the baseline at 24 weeks
- Changes of SF-12 score from the baseline at 24 weeks
Study procedure:
This open labeled randomized controlled clinical trial was conducted in the outpatient and the inpatient department of Rheumatology, BSMMU from July 2018 to September 2019. Patients of SLE were interviewed after taking verbal consent. They were screened with history, physical examination, urine RME, 24hours UTP reports. Patients fulfilling the inclusion and exclusion criteria were enrolled in the study after taking informed written consent. Total 32 patients of SLE with proliferative LN were enrolled in the study. After the enrollment study subjects were randomized into experimental group (low dose group) and control group (high dose group) by lottery. Baseline laboratory tests were urine R/M/E, 24 hours UTP, serum creatinine, anti-dsDNA, C3, C4, CBC with ESR, SGPT. Baseline quality of life was assessed by Bengali version SF-12 questionnaire.
Both groups received pulse I/V methylprednisolone 500 mg/day daily for 3 doses. Then, patients of the low dose group received oral prednisolone 0.5 mg/kg/day (maximum 30 mg/day) and high dose group received oral prednisolone 1 mg/kg/day (maximum 60 mg/day) for initial 4 weeks. In the low dose group, prednisolone was tapered by 5 mg/day in every two weeks until 10 mg/day was reached, then after two weeks the dose was tapered by 2.5 mg/day to a maintenance dose of 7.5 mg/day. In the high dose group, prednisolone was tapered by 10 mg/day in every two weeks until 40 mg, then 5 mg/day in every two weeks until 10 mg/day is reached, after two weeks it was tapered by 2.5 mg/day to a maintenance dose of 7.5 mg/day.
Patients of both groups were treated with monthly CYC infusion, first dose 750 mg/m2 body surface area, subsequent doses were adjusted based on leukocyte nadir (≥ 4000 cells/mm3, doses were increased by 25%, to a maximum of 1 gm/m2 body surface area, the dose were reduced by 25% for leukocyte counts <4000 cells/mm3). Both groups of patients received hydroxychloroquine (HCQ), angiotensin receptor blocker (ARB) and other relevant medications. Patient education, vaccinations against influenza and pneumococcus were given to all the enrolled subjects. All patients were given Pneumocystis jirovecii prophylaxes.
Primary endpoint (complete remission) was assessed at the end of 24th week. Urine R/M/E, CBC with ESR, SGPT and serum creatinine were done in every 4 weeks. Twenty-four hours UTP were done at the end of 12 weeks and 24 weeks. Anti-dsDNA, C3 and C4 were done at the end of 24 weeks. Data were collected from a set of written questionnaires which was supplied to the patients and from physical examination and investigation findings. Quality of life was assessed by Bengali version of SF-12 questionnaire.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low dose group | Experimental | Drug: PrednisolonePrednisolone 0.5 mg/kg/day |
| High dose group | Active comparator | Drug: PrednisolonePrednisolone 1 mg/kg/day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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:
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PrednisoloneAlso: PredPatients 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. | Drug | High dose group, Low dose group |
Primary outcome
Number of participants achieving complete renal remission
Time frame: 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.
1 secondary outcome
Number of participants achieving partial renal remission
Time frame: At the end of 24th week
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2019.
- Background: PubMed 22556106Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, Karpouzas GA, Merrill JT, Wallace DJ, Yazdany J, Ramsey-Goldman R, Singh K, Khalighi M, Choi SI, Gogia M, Kafaja S, Kamgar M, Lau C, Martin WJ, Parikh S, Peng J, Rastogi A, Chen W, Grossman JM; American College of Rheumatology. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken). 2012 Jun;64(6):797-808. doi: 10.1002/acr.21664. No abstract available.
- Background: PubMed 27821390Almaani 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.
- Background: PubMed 22851469Bertsias GK, Tektonidou M, Amoura Z, Aringer M, Bajema I, Berden JH, Boletis J, Cervera R, Dorner T, Doria A, Ferrario F, Floege J, Houssiau FA, Ioannidis JP, Isenberg DA, Kallenberg CG, Lightstone L, Marks SD, Martini A, Moroni G, Neumann I, Praga M, Schneider M, Starra A, Tesar V, Vasconcelos C, van Vollenhoven RF, Zakharova H, Haubitz M, Gordon C, Jayne D, Boumpas DT; European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association. Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis. 2012 Nov;71(11):1771-82. doi: 10.1136/annrheumdis-2012-201940. Epub 2012 Jul 31.
- Background: PubMed 15529366Buttgereit F, Straub RH, Wehling M, Burmester GR. Glucocorticoids in the treatment of rheumatic diseases: an update on the mechanisms of action. Arthritis Rheum. 2004 Nov;50(11):3408-17. doi: 10.1002/art.20583. No abstract available.
- Background: PubMed 23261815Seguro LP, Rosario C, Shoenfeld Y. Long-term complications of past glucocorticoid use. Autoimmun Rev. 2013 Mar;12(5):629-32. doi: 10.1016/j.autrev.2012.12.002. Epub 2012 Dec 20.
- Background: PubMed 24189280Ruiz-Irastorza G, Danza A, Perales I, Villar I, Garcia M, Delgado S, Khamashta M. Prednisone in lupus nephritis: how much is enough? Autoimmun Rev. 2014 Feb;13(2):206-14. doi: 10.1016/j.autrev.2013.10.013. Epub 2013 Nov 2.
- Background: PubMed 12833245Badsha H, Edwards CJ. Intravenous pulses of methylprednisolone for systemic lupus erythematosus. Semin Arthritis Rheum. 2003 Jun;32(6):370-7. doi: 10.1053/sarh.2002.50003.
- Background: PubMed 22271756Ruiz-Irastorza G, Danza A, Khamashta M. Glucocorticoid use and abuse in SLE. Rheumatology (Oxford). 2012 Jul;51(7):1145-53. doi: 10.1093/rheumatology/ker410. Epub 2012 Jan 23.
- Results publication: PubMed 3511372Austin HA 3rd, Klippel JH, Balow JE, le Riche NG, Steinberg AD, Plotz PH, Decker JL. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med. 1986 Mar 6;314(10):614-9. doi: 10.1056/NEJM198603063141004.
- Results publication: PubMed 1356175Boumpas 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.
- Results publication: PubMed 8815753Gourley 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.
- Results publication: PubMed 11511139Illei 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Prof. Nazrul Islam, FCPS, MD study chair
Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Prednisolone in people with Lupus Nephritis, run by Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh at 1 site in Bangladesh.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Bangladesh. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants achieving complete renal remission (time frame: At the end of 24th week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04146220, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2019.