Empagliflozin in patients with autosomal dominant polycystic kidney disease (EMPA-PKD): study protocol for a randomised controlled trial

Introduction Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary condition that causes the formation of cysts primarily in the kidneys. The continuous growth of multiple cysts leads to the destruction of functional parenchyma, which may progress to end-stage kidney disease. Tolvapta...

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Main Authors: Roland Schmitt, Sebastian Häckl, Armin Koch, Elisabeth Bahlmann-Kroll, Stefanie Kramer, Vera Christine Wulfmeyer, Julian Glandorf, Jessica Kaufeld, Dagmar Hartung, Bernhard M W Schmidt, Kai Schmidt-Ott
Format: Article
Language:English
Published: BMJ Publishing Group 2024-12-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/14/12/e088317.full
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author Roland Schmitt
Sebastian Häckl
Armin Koch
Elisabeth Bahlmann-Kroll
Stefanie Kramer
Vera Christine Wulfmeyer
Julian Glandorf
Jessica Kaufeld
Dagmar Hartung
Bernhard M W Schmidt
Kai Schmidt-Ott
author_facet Roland Schmitt
Sebastian Häckl
Armin Koch
Elisabeth Bahlmann-Kroll
Stefanie Kramer
Vera Christine Wulfmeyer
Julian Glandorf
Jessica Kaufeld
Dagmar Hartung
Bernhard M W Schmidt
Kai Schmidt-Ott
author_sort Roland Schmitt
collection DOAJ
description Introduction Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary condition that causes the formation of cysts primarily in the kidneys. The continuous growth of multiple cysts leads to the destruction of functional parenchyma, which may progress to end-stage kidney disease. Tolvaptan is the only drug specifically approved for slowing down the progression of ADPKD. Sodium-glucose transporter 2 inhibitors might provide additional benefits but there is currently no information on safety and outcome effects of SGLT2i in patients with ADPKD, as these patients were excluded in SGLT2i trials. In particular, there has been speculation that SGLT2i might increase cyst growth and accelerate the loss of kidney function in ADPKD. The EMPA-PKD trial is assessing the safety of empagliflozin in patients with rapid progressive ADPKD with and without concomitant tolvaptan use by monitoring the total kidney volume and the loss of kidney function.Methods and analysis This is an investigator-initiated, double-blind, single-centre, placebo-controlled, randomised clinical trial including patients with rapidly progressive ADPKD (n=44). Participants will be randomly allocated (1:1) to receive a daily dose of either empagliflozin (10 mg/day) or placebo for 18 months. Patients will be stratified according to concomitant tolvaptan use. The primary endpoint is the progression of cystic kidney growth by monitoring MRI-based changes in total kidney volume and the secondary endpoint is the change in glomerular filtration rate. Additional endpoints include changes in copeptin levels, albuminuria and blood pressure.Ethics and dissemination The protocol has been approved by the German Federal Institute for Drugs and Medical Devices (BfArM) after review by the independent ethics committee Landesarztekammer Rheinland-Pfalz. Participation in this study will be voluntary and informed consent will be obtained. Regardless of the outcome, the results will be disseminated through a peer-reviewed international medical journal.Trial registration numbers EU-CT number 2023-505890-34-00, NCT06391450.
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spelling doaj-art-4bc36c9d543e44539ea83227210556fe2025-08-20T01:57:59ZengBMJ Publishing GroupBMJ Open2044-60552024-12-01141210.1136/bmjopen-2024-088317Empagliflozin in patients with autosomal dominant polycystic kidney disease (EMPA-PKD): study protocol for a randomised controlled trialRoland Schmitt0Sebastian Häckl1Armin Koch2Elisabeth Bahlmann-Kroll3Stefanie Kramer4Vera Christine Wulfmeyer5Julian Glandorf6Jessica Kaufeld7Dagmar Hartung8Bernhard M W Schmidt9Kai Schmidt-Ott101 Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany2 Institute for Biostatistics, Hannover Medical School, Hannover, Germany2 Institute for Biostatistics, Hannover Medical School, Hannover, Germany1 Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany1 Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany1 Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany3 Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany1 Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany3 Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany1 Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany1 Department of Nephrology and Hypertension, Hannover Medical School, Hannover, GermanyIntroduction Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary condition that causes the formation of cysts primarily in the kidneys. The continuous growth of multiple cysts leads to the destruction of functional parenchyma, which may progress to end-stage kidney disease. Tolvaptan is the only drug specifically approved for slowing down the progression of ADPKD. Sodium-glucose transporter 2 inhibitors might provide additional benefits but there is currently no information on safety and outcome effects of SGLT2i in patients with ADPKD, as these patients were excluded in SGLT2i trials. In particular, there has been speculation that SGLT2i might increase cyst growth and accelerate the loss of kidney function in ADPKD. The EMPA-PKD trial is assessing the safety of empagliflozin in patients with rapid progressive ADPKD with and without concomitant tolvaptan use by monitoring the total kidney volume and the loss of kidney function.Methods and analysis This is an investigator-initiated, double-blind, single-centre, placebo-controlled, randomised clinical trial including patients with rapidly progressive ADPKD (n=44). Participants will be randomly allocated (1:1) to receive a daily dose of either empagliflozin (10 mg/day) or placebo for 18 months. Patients will be stratified according to concomitant tolvaptan use. The primary endpoint is the progression of cystic kidney growth by monitoring MRI-based changes in total kidney volume and the secondary endpoint is the change in glomerular filtration rate. Additional endpoints include changes in copeptin levels, albuminuria and blood pressure.Ethics and dissemination The protocol has been approved by the German Federal Institute for Drugs and Medical Devices (BfArM) after review by the independent ethics committee Landesarztekammer Rheinland-Pfalz. Participation in this study will be voluntary and informed consent will be obtained. Regardless of the outcome, the results will be disseminated through a peer-reviewed international medical journal.Trial registration numbers EU-CT number 2023-505890-34-00, NCT06391450.https://bmjopen.bmj.com/content/14/12/e088317.full
spellingShingle Roland Schmitt
Sebastian Häckl
Armin Koch
Elisabeth Bahlmann-Kroll
Stefanie Kramer
Vera Christine Wulfmeyer
Julian Glandorf
Jessica Kaufeld
Dagmar Hartung
Bernhard M W Schmidt
Kai Schmidt-Ott
Empagliflozin in patients with autosomal dominant polycystic kidney disease (EMPA-PKD): study protocol for a randomised controlled trial
BMJ Open
title Empagliflozin in patients with autosomal dominant polycystic kidney disease (EMPA-PKD): study protocol for a randomised controlled trial
title_full Empagliflozin in patients with autosomal dominant polycystic kidney disease (EMPA-PKD): study protocol for a randomised controlled trial
title_fullStr Empagliflozin in patients with autosomal dominant polycystic kidney disease (EMPA-PKD): study protocol for a randomised controlled trial
title_full_unstemmed Empagliflozin in patients with autosomal dominant polycystic kidney disease (EMPA-PKD): study protocol for a randomised controlled trial
title_short Empagliflozin in patients with autosomal dominant polycystic kidney disease (EMPA-PKD): study protocol for a randomised controlled trial
title_sort empagliflozin in patients with autosomal dominant polycystic kidney disease empa pkd study protocol for a randomised controlled trial
url https://bmjopen.bmj.com/content/14/12/e088317.full
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