Pre-emptive Treatments in Lupus Nephritis Patients With Serological Reactivation

Not Applicable

Completed

• Conditions: Lupus Nephritis
• Interventions: Procedure: Pre-emptive increase of immunosuppressive treatments; Drug: Prednisolone and/or AZA/MMF

• Registration Number: NCT04870359
• Lead Sponsor: The University of Hong Kong

Brief Summary

The optimal management of asymptomatic serological reactivation (ASR) in lupus nephritis (LN) patients remained undefined. This project aims to investigate the impact of pre-emptive treatment on disease relapse in LN patients who experienced ASR.

Detailed Description

LN patients who presented with ASR \[defined as 1) increase in anti-dsDNA \>100 IU/mL , with or without drop in serum complement; or 2) increase in anti-dsDNA to higher than the normal range and \>2 times of the preceding value, with or without drop in serum complement; and 3) Absence of renal or systemic manifestations of SLE) will be randomized to receive pre-emptive increase in immunosuppression or had their current immunosuppressive therapies unchanged.

Patients will be followed at 4-, 12-, 24-wk and then every 12 weeks up to 24 months to monitor for renal or extra-renal relapses. Bloods and urine will be collected for measurement of renal and serological parameters, and also B cell signatures.

Primary outcomes: Renal Flare (denoted as proteinuria \>1g/D; presence of urinary RBC \>30 hpf/RBC casts, or increase in SCr \>15% and positive anti-dsDNA)

Secondary outcomes:

* Safety \& tolerability of pre-emptive increase of immunosuppressive treatments

* Extra-renal flares

* Renal function at 24 months

* Changes in serological parameters

Study Timeline

• Study Start: 2016-04-21
• Study First Submitted: 2017-07-03
• Study First Submitted QC: 2021-04-28
• Study First Posted: 2021-05-03
• Primary Completion: 2022-03-31
• Study Completion: 2022-03-31
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-13
• Last Update Posted: 2024-12-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

Inclusion Criteria

• Patients with biopsy-proven lupus nephritis who experienced an episode of Asymptomatic Serological Flare (ASF) as defined by:

  1. Increase in anti-dsDNA to >100 IU/mL, with or without drop in serum complement levels OR

  2. Increase in anti-dsDNA to higher than the normal range and more than two times of the preceding value, with or without drop in serum complement levels

     AND

  3. Absence of renal or systemic manifestation of SLE.

Exclusion Criteria

1. Patients who cannot provide informed consent.
2. Patients whom the clinicians opined to have excessively high risk of infection or malignancy.
3. Patients who are pregnant or lactating.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pre-emptive Treatment (Prednisolone and/or AZA/MMF)	Pre-emptive increase of immunosuppressive treatments	1. Increase prednisolone to 0.4-0.5 mg/kg/day; taper by 5 mg every 2 weeks to reach 15mg/day; then further reduce by 2.5 mg every 2 week and aim to reach 5-7.5 mg/day after 12 weeks. 2. Adjustment of the 2nd agent would be as follows: 1. For patients who receive AZA \<75mg/day; increase the dose of AZA to 75 mg/day. 2. For patients who receive MMF \<1g/day, increase the dose of MMF to 1g/day.
Pre-emptive Treatment (Prednisolone and/or AZA/MMF)	Prednisolone and/or AZA/MMF	1. Increase prednisolone to 0.4-0.5 mg/kg/day; taper by 5 mg every 2 weeks to reach 15mg/day; then further reduce by 2.5 mg every 2 week and aim to reach 5-7.5 mg/day after 12 weeks. 2. Adjustment of the 2nd agent would be as follows: 1. For patients who receive AZA \<75mg/day; increase the dose of AZA to 75 mg/day. 2. For patients who receive MMF \<1g/day, increase the dose of MMF to 1g/day.

Primary Outcome Measures

Name	Time	Method
Renal Flare	Within 24 months	A composite endpoint denoted by proteinuria \>1g/day, presence of urinary RBC \>30/hpf or RBC casts, or increase in serum creatinine by 15% compared with baseline, and anti-DNA antibody titre above the upper limit of normal

Secondary Outcome Measures

Name	Time	Method
Infections requiring hospitalization	24 months
Extra-renal flares	24 months
Serum creatinine levels	24 months
Changes in C3	24 months
Changes in Hba1c	24 months
Changes in fasting glucose	24 months
Changes in LDL levels	24 months
Changes in anti-dsDNA	24 months

Trial Locations

Locations (2)

Queen Mary Hospital, Hong Kong; 🇭🇰 Hong Kong, Hong Kong

United Christian Hospital; 🇭🇰 Hong Kong, Hong Kong