Abstract: INFO14-FR
Protocol and Rationale for a Multi-Center, Multi-Arm, and Multi-Stage Randomized Embedded Adaptive Platform Clinical Trial in South Asian Biopsy-Proven IgA Nephropathy
Session Information
- Informational Posters - II
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- No subcategory defined
Authors
- Mani, Selvin Sundar Raj, Christian Medical College Vellore, Vellore, Tamil Nadu, India
- Varughese, Santosh, Christian Medical College Vellore, Vellore, Tamil Nadu, India
- David, Vinoi George, Christian Medical College Vellore, Vellore, Tamil Nadu, India
- Prasad, Narayan, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
- Gang, Sishir D., Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India
- Barratt, Jonathan, University of Leicester, Leicester, United Kingdom
- John, George, Queensland Health, Brisbane, Queensland, Australia
- Alexander, Suceena, Christian Medical College Vellore, Vellore, Tamil Nadu, India
Description
Background: Glomerular diseases especially IgA nephropathy are the most common cause of CKD after diabetes mellitus. South Asian ethnicity was associated with severe phenotype with rapid progression in our prospective GRACE-IgANI cohort. There is a dearth of academic pragmatic clinical trials looking at commonly available & approved generic drugs in South Asia. Platform trials with common concurrent control arm for multiple interventions ensures greater acceptability and more efficient use of resources.
Methodology: Phase IV Randomized Embedded Adaptive MAMS Platform Trial. The study hypothesis is that commonly available drugs (SGLT2 inhibitor, hydroxychloroquine, mycophenolate mofetil or low dose prednisolone) in addition to maximally tolerated RAASi can significantly improve the kidney outcomes at 2 years when compared to RAASi alone in South-Asian patients with IgAN who remain at high risk of progression. Key inclusion & exclusion criteria are summarised in Figure 1.
Primary objective is to evaluate the change in UPCR at 1 and 2 years. Efficacy Parameters: To evaluate the proportion of patients reaching the composite endpoint of ≥50% decline in eGFR, ESKD, or death at 2 years; To evaluate the mean change in total eGFR slope at 1 and 2 years; To enumerate the adverse events and medication adherence and patient related outcome measures. Exploratory objectives: To evaluate the pharmacokinetics of HCQ, mycophenolate and steroid; To evaluate the longitudinal change in serum biomarker profile from baseline to two years.
Sample size:We plan to recruit 528 patients (allocation 2:1 in control arm; 88 in each interventional arm) over 2 years.
Outcome:We will be able to generate primary evidence of clinical efficacy and toxicity of anti-proteinuric and immunomodulatory therapies for IgAN in South Asian population. Platform MAMS trial design is used for the first time in proteinuric kidney diseases which may help establish ‘GRACE- Clinical Trial Network’ for other glomerular diseases.
Funding
- DBT/ Wellcome India Alliance Senior Fellowship from 2023-2028