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

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

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.

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.

Inclusion Criteria

1. Age ≥ 18 years
2. T2DM
3. CKD (eGFR ≥ 25-60 OR UACR ≥ 30 mg/g)
4. 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.)
5. Open to start new medications

Exclusion Criteria:

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