Goal-Directed Therapy to Reduce Kidney and Cardiovascular Risk in Diabetic Kidney Disease (GOLD-STANDARD)

Official title

GOaL Directed-STrategic Approach With New Disease-modifying theraApies to Reduce Kidney and Cardiovascular Risk in Patients With Diabetic Kidney Disease

Overview

GOLD-STANDARD is a pragmatic, open-label pilot randomized controlled trial evaluating the feasibility and safety of early goal-directed Cardio-Kidney-Metabolic (CKM) care compared with usual care in patients with diabetic kidney disease. Participants will be randomized 1:1 and managed by nephrologists. The intervention includes structured kidney and cardiovascular risk assessment, early shared decision-making regarding guideline-directed medical therapies, and close monitoring for adverse effects. The usual care group will receive standard clinical management at the discretion of the treating clinician. The study will be conducted in Ontario using existing health care infrastructure.

Detailed description

GOLD-STANDARD is a parallel-group pilot randomized controlled trial designed to test early goal-directed CKM care in a real-world clinical setting. Participants will be randomized equally to the intervention or usual care arms.

Intervention Arm:

* Provides iterative assessment of kidney and cardiovascular risk to guide treatment decisions. * Implements early shared decision-making regarding initiation of guideline-directed medical therapies, following a structured 6-month protocol. The goal is to ensure each participant is offered timely treatment, though not all medications are expected to be initiated in every participant. * Supports close monitoring of side effects and treatment tolerance through multidisciplinary kidney care teams.

Usual Care Arm:

* Participants receive treatment according to standard clinical practice, with medication decisions made by the treating clinician. * Adjustments are incremental, guided by routine clinic visits and relevant biomarkers. * The trial is conducted within Ontario's health care infrastructure to evaluate the feasibility of early CKM care implementation across different clinical settings.

Interventions

• Other Early goal-directed Cardio-Kidney-Metabolic (CKM) care
  The participants in the intervention arm will be referred to a Nephrologist and receive: 1. Iterative assessment of kidney and CV risk; 2. Early shared decision making regarding starting RASi, SGLT2i, nsMRA and GLP1RA, to reduce kidney and cardiovascular risk in diabetic kidney disease (DKD). This will be informed by a 6-month GDMT protocol and supported by multidisciplinary teams and/or health care technology 3. Close monitoring of side effects.
• Other Standard care (Comparison arm)
  The standard care group will be prescribed medications based on clinical judgment by the clinician as usual care. Usual care involves incremental addition of treatment based on clinical judgment or specialty specific biomarkers (e.g. UACR) at clinic visits often spaced 3-12 months apart.

Primary outcome measures

• Feasibility of the pivotal Randomized Controlled Trial (RCT) [Time frame: From consent through completion of screening procedures to randomization (maximum 60 days).]
• Prescription and Adherence to Guideline-Directed Medical Therapy (GDMT) [Time frame: 12 months after randomization (±45-day window).]

Secondary outcome measures (12)

• Declined/ Unable to Receive Treatment - RASi [Time frame: Baseline to 12 months post-randomization (±45-day visit window).]
• Declined or Unable to Receive Treatment- SGLT2i [Time frame: Baseline to 12 months post-randomization (±45-day visit window).]
• Declined or Unable to Receive Treatment - nsMRA [Time frame: Baseline to 12 months post-randomization (±45-day visit window).]
• Declined or Unable to Receive Treatment - GLP1RA [Time frame: Baseline to 12 months post-randomization (±45-day visit window).]
• Loss to follow-up [Time frame: Baseline to 12 months post-randomization (±45-day visit window).]
• BMI [Time frame: Baseline and 12 months post-randomization (±45-day visit window)]
• Waist circumference [Time frame: Baseline and 12 months post-randomization (±45-day visit window)]
• Hip circumference [Time frame: Baseline and 12 months post-randomization (±45-day visit window)]
• Waist-to-hip ratio [Time frame: Baseline and 12 months post-randomization (±45-day visit window)]
• Blood pressure [Time frame: Baseline and 12 months post-randomization (±45-day visit window)]
• Change in Urine Albumin-to-Creatinine Ratio (UACR) [Time frame: Baseline and 12 months post-randomization (±45-day visit window)]
• Change in Estimated Glomerular Filtration Rate (eGFR) [Time frame: 12 months post-randomization (visit window ±45 days).]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• T2DM
• CKD (eGFR ≥ 25-60 OR UACR ≥ 30 mg/g)
• High Cardiovascular (CV) Risk: Defined as a history of prior myocardial infarction (MI), stroke, or peripheral artery disease (PAD), or the presence of cardiovascular risk factors, (specifically age 40 years or older and at least one of the following: cholesterol above target (LDL≥1.8 mmol/L OR on cholesterol lowering medication), hypertension (≥130/80 mmHg or on BPLMs), or atrial fibrillation.)
• Open to start new medications

Exclusion criteria

• Type 1 diabetes
• HbA1c ≥10% on screening labs
• Serum potassium ≥ 5.2 mmol/L on screening labs
• Baseline Blood Pressure (BP) < 100/60 mmHg at screening
• Treated with new or intensified immunosuppression therapy for new (or relapse/flare of pre-existing) kidney disease within the last 60 days
• Kidney Transplant
• Use of ≥3 medication classes: Participants already prescribed three or more of the following classes of medications: RASi, SGLT2i, nsMRA or GLP1RA
• Intolerance or allergy to any of RASi, SGLT2i, nsMRA or GLP1RA
• Known Heart Failure with Reduced Ejection Fraction (HFrEF)
• Current pregnancy, lactation or women of childbearing potential, unless using highly effective contraception

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Shin JI, Xu Y, Chang AR, Carrero JJ, Flaherty CM, Mukhopadhyay A, Inker LA, Blecker SB, Horwitz LI, Grams ME. Prescription Patterns for Sodium-Glucose Cotransporter 2 Inhibitors in U.S. Health Systems. J Am Coll Cardiol. 2024 Aug 20;84(8):683-693. doi: 10.1016/j.jacc.2024.05.057. PMID 39142721
• Mata-Cases M, Franch-Nadal J, Gratacos M, Mauricio D. Therapeutic Inertia: Still a Long Way to Go That Cannot Be Postponed. Diabetes Spectr. 2020 Feb;33(1):50-57. doi: 10.2337/ds19-0018. PMID 32116454
• Mebazaa A, Davison B, Chioncel O, Cohen-Solal A, Diaz R, Filippatos G, Metra M, Ponikowski P, Sliwa K, Voors AA, Edwards C, Novosadova M, Takagi K, Damasceno A, Saidu H, Gayat E, Pang PS, Celutkiene J, Cotter G. Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial. Lancet. 2022 PMID 36356631
• Savovic J, Jones HE, Altman DG, Harris RJ, Juni P, Pildal J, Als-Nielsen B, Balk EM, Gluud C, Gluud LL, Ioannidis JP, Schulz KF, Beynon R, Welton NJ, Wood L, Moher D, Deeks JJ, Sterne JA. Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. Ann Intern Med. 2012 Sep 18;157(6):429-38. doi: 10.7326/0003-4819-157-6-201209180-00537. PMID 22945832
• Campbell MJ, Julious SA, Altman DG. Estimating sample sizes for binary, ordered categorical, and continuous outcomes in two group comparisons. BMJ. 1995 Oct 28;311(7013):1145-8. doi: 10.1136/bmj.311.7013.1145. PMID 7580713
• Ong SW, Kitchlu A, Cherney DZI, Leung K, Chan CTM. Virtual Pharmacy: An Integrated Collaborative Redesign Targeting Medication-Related Problems in Patients with Chronic Kidney Disease. Am J Nephrol. 2024;55(2):206-213. doi: 10.1159/000535094. Epub 2023 Nov 8. PMID 37939689
• Lee JF, Berzan E, Sridhar VS, Odutayo A, Cherney DZI. Cardiorenal Protection in Diabetic Kidney Disease. Endocrinol Metab (Seoul). 2021 Apr;36(2):256-269. doi: 10.3803/EnM.2021.987. Epub 2021 Apr 19. PMID 33873265
• Sridhar VS, Dubrofsky L, Boulet J, Cherney DZ. Making a case for the combined use of SGLT2 inhibitors and GLP1 receptor agonists for cardiorenal protection. J Bras Nefrol. 2020 Oct-Dec;42(4):467-477. doi: 10.1590/2175-8239-JBN-2020-0100. PMID 32926067

Identifiers

NCT: NCT07434791 · CTO Project ID 5552

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗