Nephrology · Clinical trials
Chronic Kidney Disease Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About chronic kidney disease — and why its trials are hard
Chronic kidney disease (CKD) is a progressive loss of kidney function defined by reduced eGFR and/or albuminuria persisting over three months, most often driven by diabetes and hypertension. It carries high risks of kidney failure, cardiovascular events, anemia, and mineral-bone disease. Foundational therapy is renin-angiotensin system blockade with ACE inhibitors or ARBs (established by landmark trials such as RENAAL), which slow albuminuric progression. The field was transformed by SGLT2 inhibitors: dapagliflozin (DAPA-CKD, 2021) and empagliflozin (EMPA-KIDNEY, 2023) markedly reduced kidney-disease progression and cardiovascular death across diabetic and non-diabetic CKD. The non-steroidal mineralocorticoid-receptor antagonist finerenone (FIDELIO-DKD, 2021) further slows progression in diabetic kidney disease and reduces cardiovascular events. Anemia of CKD is managed with erythropoiesis-stimulating agents and the newer oral HIF prolyl-hydroxylase inhibitor daprodustat. Several once-promising agents failed on safety, including bardoxolone methyl and aliskiren, underscoring that hemodynamic or off-target harm can outweigh biomarker benefit. Care increasingly combines these pillars to preserve function and reduce cardiovascular risk.
Approved therapies & pivotal evidence
What's been approved — and by how much it moved the endpoint
| Drug (brand) | Approved | Setting | Pivotal trial | Primary endpoint | Magnitude of benefit |
|---|---|---|---|---|---|
| Losartan (Cozaar) | 2001 (nephropathy indication) | ARB, foundational renin-angiotensin blockade in type 2 diabetic nephropathy | RENAAL (NEJM 2001) | Composite of doubling of serum creatinine, end-stage kidney disease, or death | 16% relative risk reduction in the primary composite vs placebo |
| Dapagliflozin (Farxiga) | 2021 (CKD indication) | SGLT2 inhibitor for CKD with and without type 2 diabetes | DAPA-CKD (NEJM 2020) | Composite of sustained ≥50% eGFR decline, ESKD, or renal/cardiovascular death | Hazard ratio 0.61 (39% relative risk reduction) vs placebo |
| Empagliflozin (Jardiance) | 2023 (CKD indication) | SGLT2 inhibitor to reduce CKD progression and cardiovascular death | EMPA-KIDNEY (NEJM 2023) | Composite of kidney disease progression or cardiovascular death | Hazard ratio 0.72 (28% relative risk reduction) vs placebo |
| Finerenone (Kerendia) | 2021 | Non-steroidal mineralocorticoid-receptor antagonist for CKD associated with type 2 diabetes | FIDELIO-DKD (NEJM 2020) | Composite of kidney failure, sustained ≥40% eGFR decline, or renal death | Hazard ratio 0.82 (18% relative risk reduction) vs placebo |
| Daprodustat (Jesduvroq) | 2023 | Oral HIF prolyl-hydroxylase inhibitor for anemia of CKD in patients on dialysis | ASCEND-D (NEJM 2021) | Change in hemoglobin and cardiovascular safety (MACE non-inferiority) | Non-inferior hemoglobin correction and MACE vs conventional ESAs (HR ~1.03) |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in chronic kidney disease development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| Bardoxolone methyl (Nrf2 activator) — BEACON | Trial terminated early; raised eGFR biomarker but caused excess heart failure/fluid overload and cardiovascular events without hard-outcome benefit; FDA declined approval (2022, CARDINAL/Alport) | Fluid retention and heart-failure hospitalizations; eGFR increase reflected hemodynamic effect rather than durable kidney protection |
| Aliskiren (direct renin inhibitor) — ALTITUDE | Halted early for futility and harm when added to ACE inhibitor/ARB in type 2 diabetes with renal/cardiovascular risk | No benefit plus increased hyperkalemia, hypotension, and non-fatal stroke from dual RAS blockade |
| Roxadustat (HIF-PHI) — Pooled anemia-of-CKD program | FDA declined approval in the US (2021) for anemia of CKD | Thrombotic and cardiovascular safety concerns judged to outweigh the hemoglobin benefit |
Choosing the right endpoint
Primary endpoints that matter in chronic kidney disease trials
- eGFR slope / sustained eGFR decline — Rate of kidney function loss; sustained ≥40% or ≥50% decline used in composite endpoints
- End-stage kidney disease (ESKD) — Progression to dialysis or transplant; a definitive hard kidney outcome
- Albuminuria (UACR) — Marker of glomerular injury and an early treatment-response and risk endpoint
- Cardiovascular death / MACE — Captures the tightly linked cardiovascular risk of CKD; part of key composites
- Hemoglobin (anemia of CKD) — Primary efficacy measure for ESAs and HIF-PHIs, paired with cardiovascular safety
How iNGENū runs chronic kidney disease trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
Request a fixed-milestone proposal and a tailored endpoint & feasibility summary for this indication.
Frequently asked questions
Chronic Kidney Disease clinical trials — FAQs
Why are SGLT2 inhibitors now central to CKD care?
How does finerenone differ from older MRAs?
Why did bardoxolone methyl fail?
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