Childhood-onset Lupus Nephritis Initial Glucocorticoid-dose Harmonization Trial (LIGHT Trial)
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age6-18
SponsorPeking Union Medical College Hospital
About this trial
Childhood-onset systemic lupus erythematosus (cSLE) is a severe chronic autoimmune disease with a high burden of major-organ involvement. Lupus nephritis (LN) affects more than half of children with SLE, and proliferative LN-including class III, IV, III+V, and IV+V disease-is associated with acute kidney injury, progression to end-stage kidney disease, and poor long-term outcomes.
Glucocorticoids remain a cornerstone of induction therapy for proliferative LN. However, the optimal initial dose in children is uncertain. Although recent adult SLE and LN guidelines increasingly recommend lower-dose glucocorticoid regimens with rapid tapering, pediatric guidelines still commonly recommend high initial prednisone doses of 1.5-2.0 mg/kg/day. Adult trials and comparative observational studies suggest that lower-dose glucocorticoid regimens may preserve efficacy while reducing treatment-related toxicity.
Because cumulative glucocorticoid exposure in children may impair growth, development, psychosocial well-being, and medication adherence, this trial will compare low-dose versus high-dose initial glucocorticoid regimens for induction treatment of pediatric proliferative LN. The objective is to determine whether a lower-dose regimen is non-inferior in efficacy while reducing glucocorticoid-related adverse effects and improving quality of life.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥6 years and <18 years, with body weight ≥20 kg
Meets the 2019 European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) classification criteria for Systemic Lupus Erythematosus (SLE)
Renal biopsy confirming Lupus Nephritis class III, IV, III+V, or IV+V according to the International Society of Nephrology / Renal Pathology Society (ISN/RPS) classification
At screening: 24-hour urinary protein ≥1.0 g (or ≥25 mg/kg), or urine protein-to-creatinine ratio (UPCR) ≥1.0 g/g
Disqualifiers
Uncertain diagnosis of SLE, genetically confirmed monogenic lupus, or a history of immunodeficiency
Severe infection, including hepatitis C, active hepatitis B, HIV infection, tuberculosis infection, severe fungal infection, etc.
Severe neuropsychiatric lupus
Peripheral blood hemoglobin <60 g/L, platelet count <10 × 10⁹/L, or concomitant aplastic anemia
Trial design
Design model
Parallel
Treatments tested in this trial
High-dose prednisone
DrugAll participants will receive two courses of intravenous methylprednisolone pulse therapy (10-30 mg/kg/day for 3 consecutive days per course; maximum 500 mg/day). Participants will then be randomized in a 1:1 ratio to the two treatment groups. In the standard-dose (control) group, oral prednisone will be initiated at 1.4-1.6 mg/kg/day (maximum 60 mg/day), followed by gradual tapering according to the predefined schedule. For participants weighing \<40 kg, doses will be adjusted in proportion to body weight using the following formula: Individual dose = standard dose × body weight (kg) × 0.025. All participants will receive background therapy with oral hydroxychloroquine, mycophenolate mofetil, and intravenous belimumab at standard doses.
Low-dose prednisone
DrugAll participants will receive two courses of intravenous methylprednisolone pulse therapy (10-30 mg/kg/day for 3 consecutive days per course; maximum 500 mg/day). Participants will then be randomized in a 1:1 ratio to the two treatment groups. Participants in the intervention group will receive oral prednisone at an initial dose of 0.6-0.8 mg/kg/day, with a maximum dose of 30 mg/day, followed by gradual tapering according to the predefined schedule. For participants weighing \<40 kg, doses will be adjusted in proportion to body weight using the following formula: Individual dose = standard dose × body weight (kg) × 0.025. The estimated cumulative prednisone dose over 24 weeks will be approximately 50% of that in the control group. All participants will receive background therapy with oral hydroxychloroquine, mycophenolate mofetil, and intravenous belimumab at standard doses.
Treatment groups
198 Participants
are divided into 2 treatment groupsGroup A: Control group (High-dose group)Active comparator 1 intervention
Group B: Intervention group (Low-dose group)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Total Renal Response at Week 24
Total renal response (TRR) is defined as achievement of complete renal response (CRR), primary efficacy renal response (PERR), or partial renal response (PRR). Complete renal response (CRR) is defined as meeting both of the following criteria: 1. Proteinuria \<0.5 g/1.73 m², or 24-hour urinary protein excretion \<300 mg/m², or urine protein-to-creatinine ratio (UPCR) \<0.5 g/g; and 2. Estimated glomerular filtration rate (eGFR) within the normal range, or eGFR ≥85% of baseline, or a normal serum creatinine level with an increase of no more than 25% from baseline. Primary efficacy renal response (PERR) is defined as meeting both of the following criteria: 1. UPCR \<0.7 g/g; and 2. eGFR ≥80% of baseline or eGFR ≥60 mL/min/1.73 m². Partial renal response (PRR) is defined as meeting both of the following criteria: 1. A ≥50% reduction in proteinuria from baseline and UPCR \<3 g/g; and 2. eGFR ≥85% of baseline.
Time frame
Week 24Secondary outcomes
1
Complete Renal Response at Week 12 and 24
CRR is defined as meeting both of the following criteria: (1) Urine protein \<0.5 g/1.73 m², or 24-hour urine protein \<300 mg/m², or urine protein-to-creatinine ratio (UPCR) \<0.5 g/g; AND (2) Estimated glomerular filtration rate (eGFR) within the normal range; or eGFR at least 85% of baseline; or normal serum creatinine with an increase of no more than 25% from baseline.
Time frame
Week 12, 242
Primary Efficacy Renal Response at Week 12 and 24
PERR is defined as meeting both of the following criteria: (1) UPCR \<0.7 g/g; AND (2) eGFR at least 80% of baseline or eGFR ≥60 mL/min/1.73 m².
Time frame
Week 12, 243
Partial Renal Response at Week 12 and 24
PRR is defined as meeting both of the following criteria: (1) Urine protein reduced by ≥50% from baseline and UPCR \<3 g/g; AND (2) eGFR at least 85% of baseline.
Time frame
Week 12, 244
Time to TRR
Total renal response (TRR) is defined as achievement of complete renal response (CRR), primary efficacy renal response (PERR), or partial renal response (PRR). Complete renal response (CRR) is defined as meeting both of the following criteria: 1. Proteinuria \<0.5 g/1.73 m², or 24-hour urinary protein excretion \<300 mg/m², or urine protein-to-creatinine ratio (UPCR) \<0.5 g/g; and 2. Estimated glomerular filtration rate (eGFR) within the normal range, or eGFR ≥85% of baseline, or a normal serum creatinine level with an increase of no more than 25% from baseline. Primary efficacy renal response (PERR) is defined as meeting both of the following criteria: 1. UPCR \<0.7 g/g; and 2. eGFR ≥80% of baseline or eGFR ≥60 mL/min/1.73 m². Partial renal response (PRR) is defined as meeting both of the following criteria: 1. A ≥50% reduction in proteinuria from baseline and UPCR \<3 g/g; and 2. eGFR ≥85% of baseline.
Time frame
Week 0-24Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Peking Union Medical College Hospital
Lead sponsor
Children's Hospital of Chongqing Medical University
Collaborator
Beijing Children's Hospital
Collaborator
Second Xiangya Hospital of Central South University
Collaborator
Shenzhen Children's Hospital
Collaborator
Nanjing Children's Hospital
Collaborator
Jilin University
Collaborator
Children's Hospital of Fudan University
Collaborator
Source ClinicalTrials.gov