Gansevoort, Ron T;
Wheeler, David C;
Martínez Debén, Francisco;
Speeckaert, Marijn;
Thomas, Dirk;
Berger, Mario;
Klein, Stefan;
... Schmieder, Roland E; + view all
(2024)
The soluble guanylate cyclase activator runcaciguat significantly improves albuminuria in patients with chronic kidney disease: a randomized placebo-controlled clinical trial.
Nephrology Dialysis Transplantation
10.1093/ndt/gfae261.
(In press).
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Abstract
BACKGROUND AND HYPOTHESIS: In chronic kidney disease (CKD) the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway is impaired. Runcaciguat, an sGC activator, activates heme-free sGC, restoring cGMP production. This phase 2a trial studied the efficacy, safety, and tolerability of runcaciguat in CKD patients with or without sodium-glucose co-transporter-2 inhibitor (SGLT2i). METHODS: Patients with CKD and established atherosclerotic cardiovascular disease or heart failure, plus type 2 diabetes (T2D) and/or hypertension, were enrolled. All were receiving stable maximum tolerated renin - angiotensin system inhibitors with or without SGLT2i. They were randomized 3:1 to runcaciguat once daily, titrated weekly (30-120 mg if tolerated), or placebo for 8 weeks. The primary efficacy endpoint was urine albumin-to-creatinine ratio (UACR) (average of post-randomization Days 22, 29, and 57 vs baseline). CONCORD was separately powered for CKD and T2D with stable SGLT2i comedication, CKD and T2D without SGLT2i, and non-diabetic CKD. RESULTS: Of 243 patients randomized, 229 were included in the full analysis set (FAS) and 170 in the per-protocol set (PPS). In the PPS, UACR decreased by - 45.2% versus placebo with runcaciguat in patients with CKD without SGLT2i (P < 0.001) and by - 48.1% versus placebo in patients with CKD taking SGLT2i (P = 0.02) In the FAS, the relative reductions were - 46.9% (P < 0.001) and - 44.8% (P = 0.01), respectively. No significant difference was observed between patients with or without SGLT2i. In non-diabetic CKD, UACR was reduced versus baseline with runcaciguat, but the change was not statistically significant (P = 0.10). Serious treatment-emergent adverse events were reported in 7% of patients receiving runcaciguat and 8% receiving placebo. CONCLUSION: Runcaciguat improved albuminuria in patients with CKD, irrespective of concomitant SGLT2i. Runcaciguat was well tolerated. sGC activation may represent a novel kidney-protective treatment in CKD patients (funded by Bayer AG; ClinicalTrials.gov number, NCT04507061).
| Type: | Article |
|---|---|
| Title: | The soluble guanylate cyclase activator runcaciguat significantly improves albuminuria in patients with chronic kidney disease: a randomized placebo-controlled clinical trial |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/ndt/gfae261 |
| Publisher version: | https://doi.org/10.1093/ndt/gfae261 |
| Language: | English |
| Additional information: | Copyright © The Author(s) 2024. Published by Oxford University Press on behalf of the ERA. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com. |
| Keywords: | albuminuria, chronic kidney disease, sodium-glucose co-transporter-2 inhibitors, soluble guanylate cyclase activator, type 2 diabetes |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10202753 |
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