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

NCT07434791 | Not Yet Recruiting

• 1 other identifier: CTO Project ID 5552
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Diabetic Kidney Disease (DKD)

Keywords

diabetes; diabetic kidney disease; cardiovascular risk; Cardio-Kidney-Metabolic (CKM) care

Outcome Measures

Primary Outcomes (2)

• Feasibility of the pivotal Randomized Controlled Trial (RCT)

  Percentage of consenting participants who are eligible and randomized. Feasibility is defined as ≥40% of consented and screened participants meeting criteria and being randomized.

  From consent through completion of screening procedures to randomization (maximum 60 days).

• Prescription and Adherence to Guideline-Directed Medical Therapy (GDMT)

  Determined based on the percentage of people prescribed and adherent to GDMT at 12 months when assessed on an ordinal scale from 1 to 4 medications.

  12 months after randomization (±45-day window).

Secondary Outcomes (22)

• Declined/ Unable to Receive Treatment - RASi

  Baseline to 12 months post-randomization (±45-day visit window).

• Declined or Unable to Receive Treatment- SGLT2i

  Baseline to 12 months post-randomization (±45-day visit window).

• Declined or Unable to Receive Treatment - nsMRA

  Baseline to 12 months post-randomization (±45-day visit window).

• Declined or Unable to Receive Treatment - GLP1RA

  Baseline to 12 months post-randomization (±45-day visit window).

• Loss to follow-up

  Baseline to 12 months post-randomization (±45-day visit window).

Study Arms (2)

Comparison Arm

ACTIVE COMPARATOR

Standard of care

Other: Standard care (Comparison arm)

Intervention arm

EXPERIMENTAL

CKM

Other: Early goal-directed Cardio-Kidney-Metabolic (CKM) care

Interventions

Early goal-directed Cardio-Kidney-Metabolic (CKM) care OTHER

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.

Intervention arm

Standard care (Comparison arm) OTHER

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.

Comparison Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Kidney Foundation of Canada: collaborator
• Sunnybrook Health Sciences Centre: lead

Related Publications (25)

• Shin JI, Xu Y, Chang AR, Carrero JJ, Flaherty CM, Mukhopadhyay A, et al. Prescription Patterns for Sodium-Glucose Cotransporter 2 Inhibitors in U.S. Health Systems. J Am Coll Cardiol. 2024 Aug 20;84(8):683-93.

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• Mata-Cases M, Franch-Nadal J, Gratacòs M, Mauricio D. Therapeutic Inertia: Still a Long Way to Go That Cannot Be Postponed. Diabetes Spectr. 2020 Feb;33(1):50-7.

  BACKGROUND

• Mebazaa A, Davison B, Chioncel O, Cohen-Solal A, Diaz R, Filippatos G, et al. 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 Dec 3;400(10367):1938-52.

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• Savović J, Jones HE, Altman DG, Harris RJ, Jüni P, Pildal J, et al. Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. 2012 Sep;157(6):429-38.

  BACKGROUND

• 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.

  BACKGROUND

• 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. 2023 Nov 8;

  BACKGROUND

• Savović J, Jones HE, Altman DG, Harris RJ, Jüni P, Pildal J, et al. Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. 2012 Sept;157(6):429-38.

  BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Albakr RB, Sridhar VS, Cherney DZI. Novel Therapies in Diabetic Kidney Disease and Risk of Hyperkalemia: A Review of the Evidence From Clinical Trials. Am J Kidney Dis. 2023 Dec;82(6):737-742. doi: 10.1053/j.ajkd.2023.04.015. Epub 2023 Jul 29.

  PMID: 37517546 BACKGROUND

• Yau K, Odutayo A, Dash S, Cherney DZI. Biology and Clinical Use of Glucagon-Like Peptide-1 Receptor Agonists in Vascular Protection. Can J Cardiol. 2023 Dec;39(12):1816-1838. doi: 10.1016/j.cjca.2023.07.007. Epub 2023 Jul 8.

  PMID: 37429523 BACKGROUND

• Yau K, Dharia A, Alrowiyti I, Cherney DZI. Prescribing SGLT2 Inhibitors in Patients With CKD: Expanding Indications and Practical Considerations. Kidney Int Rep. 2022 July;7(7):1463-76.

  BACKGROUND

• Green JB, Mottl AK, Bakris G, Heerspink HJL, Mann JFE, McGill JB, et al. Design of the COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint study (CONFIDENCE). Nephrol Dial Transplant. 2023 Mar 31;38(4):894-903

  BACKGROUND

• Brahmbhatt DH, Ross HJ, O'Sullivan M, Artanian V, Mueller B, Runeckles K, et al. The Effect of Using a Remote Patient Management Platform in Optimizing Guideline-Directed Medical Therapy in Heart Failure Patients: A Randomized Controlled Trial. JACC Heart Fail. 2024 Apr;12(4):678-90.

  BACKGROUND

• Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, et al. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020 Dec 3;383(23):2219-29.

  BACKGROUND

• Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, Cannon CP, Capuano G, Chu PL, de Zeeuw D, Greene T, Levin A, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Meininger G, Brenner BM, Mahaffey KW; CREDENCE Trial Investigators. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019 Jun 13;380(24):2295-2306. doi: 10.1056/NEJMoa1811744. Epub 2019 Apr 14.

  PMID: 30990260 BACKGROUND

• American Diabetes Association. Introduction: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022 Jan 1;45(Suppl 1):S1-2.

  BACKGROUND

• Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2022 Nov;102(5S):S1-S127. doi: 10.1016/j.kint.2022.06.008. No abstract available.

  PMID: 36272764 BACKGROUND

• Agarwal R, Green JB, Heerspink HJL, Mann JFE, McGill JB, Mottl AK, et al. Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes. N Engl J Med. 2025 Jun 5

  BACKGROUND

• Apperloo EM, Neuen BL, Fletcher RA, Jongs N, Anker SD, Bhatt DL, et al. Efficacy and safety of SGLT2 inhibitors with and without glucagon-like peptide 1 receptor agonists: a SMART-C collaborative meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol. 2024 Aug;12(8):545-57

  BACKGROUND

• Neuen BL, Fletcher RA, Heath L, Perkovic A, Vaduganathan M, Badve SV, et al. Cardiovascular, Kidney, and Safety Outcomes With GLP-1 Receptor Agonists Alone and in Combination With SGLT2 Inhibitors in Type 2 Diabetes: A Systematic Review and Meta-Analysis. Circulation. 2024 Nov 26;150(22):1781-90.

  BACKGROUND

• Afkarian M, Sachs MC, Kestenbaum B, Hirsch IB, Tuttle KR, Himmelfarb J, et al. Kidney Disease and Increased Mortality Risk in Type 2 Diabetes. Journal of the American Society of Nephrology. 2013 Jan;24(2):302-8.

  BACKGROUND

• Lemley KV, Abdullah I, Myers BD, Meyer TW, Blouch K, Smith WE, et al. Evolution of incipient nephropathy in type 2 diabetes mellitus. Kidney Int. 2000 Sep;58(3):1228-37

  BACKGROUND

• Mathiesen ER, Ronn B, Storm B, Foght H, Deckert T. The natural course of microalbuminuria in insulin-dependent diabetes: a 10-year prospective study. Diabet Med. 1995 Jun;12(6):482-7. doi: 10.1111/j.1464-5491.1995.tb00528.x.

  PMID: 7648820 BACKGROUND

• Chu L, Fuller M, Jervis K, Ciaccia A, Abitbol A. Prevalence of Chronic Kidney Disease in Type 2 Diabetes: The Canadian REgistry of Chronic Kidney Disease in Diabetes Outcomes (CREDO) Study. Clin Ther. 2021 Sep;43(9):1558-1573. doi: 10.1016/j.clinthera.2021.07.015. Epub 2021 Aug 21.

  PMID: 34426012 BACKGROUND

MeSH Terms

Conditions

Diabetic Nephropathies; Diabetes Mellitus

Interventions

Creatine Kinase, MM Form; Standard of Care

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Creatine Kinase; Phosphotransferases (Nitrogenous Group Acceptor); Phosphotransferases; Transferases; Enzymes; Enzymes and Coenzymes; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Central Study Contacts

Kristina Hyunjee Lee, M.Ed

CONTACT

437-869-7138; Gold-standard@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: February 27, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: May 7, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share