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Atrasentan in patients with IgA nephropathy (ALIGN): final 2·5-year results from a randomised, double-blind, placebo-controlled, phase 3 trial.
This randomised, double-blind, placebo-controlled phase 3 trial tested atrasentan, an endothelin A receptor blocker, in adults with biopsy-proven IgA neph…
Signal score64Research triage score
CertaintyLow-to-moderateVerify in full text
PMID42242268Source identifier
Research triage, not medical advice
Do not use this summary, score, or benefit-cost estimate to diagnose, treat, prescribe, or change care without reviewing the full study and consulting qualified professionals.
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Check full-text methods, eligibility, outcomes, risk of bias, harms, conflicts, funding, replication, and applicability.
Plain-English signal
This randomised, double-blind, placebo-controlled phase 3 trial tested atrasentan, an endothelin A receptor blocker, in adults with biopsy-proven IgA nephropathy who were already on renin-angiotensin system inhibition. Over 2.5 years, atrasentan reduced protein in the urine and slowed the decline in estimated kidney function (eGFR) compared with placebo. The overall difference in eGFR change at study end narrowly missed conventional statistical significance for the main analysis (p=0.057), but treatment preserved kidney function on several analyses, and benefit appeared larger in participants also taking an SGLT2 inhibitor. Adverse events were generally balanced between groups, with similar rates of fluid retention. Full-text review is required before clinical decisions or policy changes.
Why it matters
- IgA nephropathy is a leading cause of progressive chronic kidney disease; interventions that slow eGFR decline could change long-term risk of kidney failure and need for kidney replacement therapy.
- Atrasentan is an endothelin A receptor antagonist that reduced proteinuria earlier in this trial; proteinuria reduction and slower eGFR decline are clinically relevant outcomes for nephrology practice and guideline panels.
- The trial reports 2.5-year kidney function outcomes (eGFR change and slope) and includes a prespecified exploratory stratum with concomitant SGLT2 inhibitor use, which is relevant for current standard-of-care combinations.
Primary outcomes
- Key secondary endpoint (as described in abstract): change from baseline to week 136 in eGFR in the main stratum, assessed in all randomised patients (excluding data after intercurrent events such as initiation of restricted/alternative IgA nephropathy medications or kidney replacement therapy).
Effect summary
Abstract-reported results: In the main stratum (n=340), eGFR change at week 136 was -7.5 mL/min/1.73 m2 with atrasentan vs -9.9 mL/min/1.73 m2 with placebo (between-group difference 2.4 mL/min/1.73 m2; 95% CI -0.1 to 4.8; p=0.057). End-of-treatment difference at week 132 was 2.6 mL/min/1.73 m2 (95% CI 0.1-5.0). Total eGFR slope difference was 1.4 mL/min/1.73 m2 per year (95% CI 0.5-2.3). In the SGLT2 inhibitor stratum (n=64), difference at week 136 was 9.1 mL/min/1.73 m2 (95% CI 3.0-15.2). Proteinuria was reduced in prior interim analyses. Treatment-emergent adverse events were balanced; fluid retention occurred in 14% on atrasentan vs 12% on placebo in the main stratum.
Benefit-cost lens
| Quick take | Promising signal for kidney preservation in IgA nephropathy, but decision-relevant benefit-cost claims require full-text data, absolute event rates, costs, and target-population estimates. |
|---|---|
| BCR anchor | 2 |
| Time horizon | 3 |
| Discount rate | 0.03 |
| Assumptions | Assessment based solely on PubMed metadata and abstract; full text may alter effect estimates, safety, subgroup findings, and applicability. |
Benefit-cost fields are assumptions-based unless explicitly source-derived. Treat them as prompts for deeper economic review.
Risk of bias
| Tool | rapid-abstract-screen |
|---|---|
| Verdict | Some concerns |
| Notes | Phase 3 randomized, double-blind design reduces bias risk, but assessment is limited to abstract: details on randomisation sequence generation, allocation concealment, handling of missing data and intercurrent events, and full safety reporting require full-text review. |
Harms, equity, conflicts & implementation
| Implementation | Full-text review, regulatory status confirmation, cost and formulary assessment, monitoring plans for fluid retention and other adverse events, integration with SGLT2 inhibitor use, and local eligibility criteria mapping. |
|---|---|
| Equity impact | Unclear from abstract; equity implications depend on access to atrasentan, differential baseline risk across populations, and reported subgroup effects in full text. |
| Harms | Abstract reports balanced overall adverse events and similar rates of fluid retention (14% vs 12%); no new safety signals per abstract. Full adverse-event breakdown and severity grading require full-text review. |
| Funding | Novartis (reported in abstract as funder) |
| Registration | NCT04573478 |
| Replication | Unknown from abstract; no replication data reported. |
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