Rationale and design of NUDGE-CKD: A nationwide randomized factorial trial of electronic nudges for increasing guideline-directed medical therapy in chronic kidney disease
- PMID: 40174694
- DOI: 10.1016/j.ahj.2025.03.015
Rationale and design of NUDGE-CKD: A nationwide randomized factorial trial of electronic nudges for increasing guideline-directed medical therapy in chronic kidney disease
Abstract
Background: Treatment guidelines for chronic kidney disease (CKD) recommend sodium-glucose cotransporter 2 inhibitors (SGLT2i) as first-line treatment for a broad range of individuals with CKD, alongside renin-angiotensin system inhibitors (RASi). However, adoption of guidelines in clinical practice is often delayed, potentially leading to avoidable associated morbidity and mortality. Effective strategies are needed to improve implementation of guideline-directed medical therapy (GDMT) in patients with CKD. This trial will evaluate the effectiveness of electronic letter-based nudges, delivered via the Danish governmental electronic letter system to individuals with CKD, their general practices, or both, in increasing GDMT in individuals with CKD.
Methods: NUDGE-CKD is a 2 × 2 factorial, nationwide implementation trial, with randomization at both the general practice and patient level. All Danish citizens with CKD and access to the official Danish electronic letter system were randomized in a 1:1 ratio to usual care (no letter) or to receive an electronic letter-based nudge on GDMT in CKD. All Danish general practices with a patient with CKD on their patient panel were also randomized 1:1 to usual care (no letter) or to receive an electronic informational nudge letter on GDMT in CKD. Data are collected through the Danish administrative health registries. The primary endpoint is a prescription of RASi or SGLT2i within 6 months of intervention delivery based on fill records. Secondary endpoints include components of the primary endpoint, as well as proportion of new CKD GDMT users. Prespecified exploratory endpoints include filled prescriptions of other cardio-renal-protective medications, general practice contacts, assessment of renal biomarkers and downstream clinical outcomes. A total 22,617 individuals with CKD were randomized to the patient-level intervention, and 28,069 individuals with CKD across 1,540 general practices were randomized to the general practice-level intervention. Intervention letters were delivered on August 19, 2024, and follow-up is currently ongoing (end of follow-up for primary endpoint: February 19, 2025).
Discussion: NUDGE-CKD is the first nationwide randomized trial of electronic letter-based nudges delivered to individuals with CKD and their general practices to increase uptake of GDMT in individuals with CKD. The trial will provide evidence into the usefulness of direct communication with patients and healthcare providers for real-world implementation of GDMT.
Trial registration: Clinicaltrials.gov: NCT06300086, registered March 7, 2024 (https://clinicaltrials.gov/study/NCT06300086).
Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of competing interest KGS served on an advisory board for Sanofi; received financial support for congress participation from AstraZeneca outside the submitted work. BLC reported receiving consulting fees from Alnylam, Cardurion, Corvia, Cytokinetics, Intellia, Rocket, CVRX, BMS, and Eli Lilly outside the submitted work. MV reported receiving research grant support from American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, BMS, Boehringer Ingelheim, Chiesi, Cytokinetics, Fresenius Medical Care, Idorsia Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Milestone Pharmaceuticals, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health, serving on advisory boards and clinical trial committees or having speaker engagements and receiving grants from AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics outside the submitted work. ASB reported receiving speaker engagement fees from Sanofi, Merck, AstraZeneca, and Novo Nordisk outside the submitted work. HVS received grants from the Canadian Institutes of Health Research and Heart and Stroke Foundation, education grants from Boehringer Ingelheim and Novartis and consulting fees from the Baim Institute for Clinical Research, Cardiovascular Research Foundation, Colorado Prevention Center Clinical Research, Novo Nordisk, and Medtronic outside the submitted work. MKL received speaker fees and/or served on advisory boards for Novo Nordisk, AstraZeneca, Bayer, Boehringer Ingelheim, GlaxoSmithKline; received research support from Novo Nordisk A/S, AstraZeneca, Bayer, Boehringer Ingelheim, and MSD. TK reports speaker fees from AstraZeneca outside the submitted work. ADT reports speaker fees from AstraZeneca and Boehringer Ingelheim outside the submitted work. MGK received a research grant from AstraZeneca outside the submitted work. JDK received consulting fees from Baxter; received financial support for travel for congress participation from AstraZeneca outside the submitted work. MH served on advisory boards for Novo Nordisk, Bayer, Boehringer Ingelheim, GlaxoSmithKline, CLS Vifor, and AstraZeneca; received speaker fees from Novo Nordisk, AstraZeneca, and Boehringer Ingelheim; received research grants from Boehringer Ingelheim, AstraZeneca, Novo Nordisk, Novartis, and Dimerix Bioscience Inc outside the submitted work. FZ received consulting fees from 89bio, Applied Therapeutics, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior Pharmaceuticals, CellProthera, Cereno Scientific, CEVA, CVRx, Merck, Novartis, Novo Nordisk, Owkin, Pfizer and Servier, honoraria for lectures from Bayer, Boehringer Ingelheim, CEVA, CVRx, Merck and Novartis and fees for participating on a data safety monitoring board or advisory board from Acceleron/Merck and has equity interests in G3 Pharmaceuticals, Cereno Scientific, CardioRenal, Eshmoun Clinical Research and CVCT outside the submitted work. SDS reported receiving grants from Alexion, Alnylam, Applied Therapeutics, AstraZeneca, Bellerophon, Bayer, BMS, Boston Scientific, Cytokinetics, Edgewise, Eidos/BridgeBio, Gossamer, GSK, Ionis, Lilly, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Tenaya, Theracos, and US2.AI and personal fees from Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, BMS, Cardior, Cardurion, Corvia, Cytokinetics, GSK, Lilly, Novartis, Roche, Theracos, Quantum Genomics, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo outside the submitted work. RB reports serving on research boards and/or receiving speaker fees from Novo Nordisk, AstraZeneca, Bayer, and Boehringer Ingelheim; received research grants from AstraZeneca and Boehringer Ingelheim outside the submitted work. HB reports speaker fees and/or serving on advisory boards for Novo Nordisk, AstraZeneca, Bayer, Boehringer Ingelheim, Galapagos, GlaxoSmithKline, Alexion, Otsuka Pharmaceuticals, MSD, and Vifor Pharma; received research grants from GlaxoSmithKline and Vifor Pharma; serves as chairman of the Danish Society of Nephrology outside the submitted work. DH reports research grants from Vifor Pharma and Gedeon Richter; received consultancy fees and speaker fees from UCB Nordic, GlaxoSmithKline, and AstraZeneca. TBS has received research grants from Novartis, Pfizer, Sanofi Pasteur, GSK, Novo Nordisk, AstraZeneca, Boston Scientific and GE Healthcare, consulting fees from Novo Nordisk, IQVIA, Parexel, Amgen, CSL Seqirus, GSK and Sanofi Pasteur, and lecture fees from AstraZeneca, Bayer, Novartis, Sanofi Pasteur, GE healthcare and GSK. All other authors declare no competing interests.
Publication types
MeSH terms
Substances
Associated data
LinkOut - more resources
Full Text Sources
Medical
