Pre-emptive Treatments in Lupus Nephritis Patients With Serological Reactivation

Pre-emptive Increase of Immunosuppressive Treatments in Lupus Nephritis Patients With Asymptomatic Serological Reactivation

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Desmond YH YAP, MBBS (HK), MD (HK); Phone Number: 85222554385; Email: desmondy@hku.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • United Christian Hospital
  • Hong Kong, Hong Kong
    • Recruiting
    • Queen Mary Hospital, Hong Kong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Pre-emptive Treatment (Prednisolone and/or AZA/MMF); 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.; Adjustment of the 2nd agent would be as follows:For patients who receive AZA <75mg/day; increase the dose of AZA to 75 mg/day.For patients who receive MMF <1g/day, increase the dose of MMF to 1g/day.	Procedure: Pre-emptive increase of immunosuppressive treatments; 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.; Adjustment of the 2nd agent would be as follows:For patients who receive AZA <75mg/day; increase the dose of AZA to 75 mg/day.For patients who receive MMF <1g/day, increase the dose of MMF to 1g/day.; Drug: Prednisolone and/or AZA/MMF; Prednisolone and/or AZA/MMF
NO_INTERVENTION: Control; Current immunosuppressive regimen and dosage should remain unchanged until the development of renal or extra-renal flares which required increase/change in immunosuppression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal Flare	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	Within 24 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Collaborators: United Christian Hospital
• Investigators: Principal Investigator: Desmond YH Yap, MBBS (HK). MD (HK), Queen Mary Hospital, the University of Hong Kong

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 21, 2016
• Primary Completion (ANTICIPATED): March 31, 2023
• Study Completion (ANTICIPATED): March 31, 2023

Study Registration Dates

• First Submitted: July 3, 2017
• First Submitted That Met QC Criteria: April 28, 2021
• First Posted (ACTUAL): May 3, 2021

Study Record Updates

• Last Update Posted (ACTUAL): July 26, 2022
• Last Update Submitted That Met QC Criteria: July 25, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisolone; Immunosuppressive Agents
• Other Study ID Numbers: UW-16-074

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No