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

Sunnybrook Health Sciences Centre100 enrolled

Overview

GOLD-STANDARD is a pragmatic, open-label pilot randomized controlled trial evaluating the feasibility, safety, and implementation of an early goal-directed Cardio-Kidney-Metabolic (CKM) care strategy compared with usual care in adults with type 2 diabetes and diabetic kidney disease who are at increased cardiovascular risk. Participants will be followed for 12 months to assess treatment uptake, adherence, retention, and safety outcomes, and to inform the design of a future definitive trial.

The GOLD-STANDARD study will evaluate the feasibility of an early, goal-directed Cardio-Kidney-Metabolic (CKM) care strategy that integrates kidney, cardiovascular, and metabolic risk management within routine nephrology practice. Using a pragmatic randomized design, the study will assess whether a structured approach to CKM care can be implemented safely and effectively within Ontario's healthcare system. The primary objective of this pilot study is to evaluate feasibility, including recruitment, retention, treatment implementation, and adherence. Safety and treatment uptake measures will also be assessed over 12 months of follow-up. Findings from this study will inform the design and conduct of a future large-scale trial evaluating the impact of early CKM care on clinical kidney and cardiovascular outcomes.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

HEALTH_SERVICES_RESEARCH

Masking

SINGLE

Enrollment

100

Conditions

Diabetic Kidney Disease (DKD)

Interventions

Early goal-directed Cardio-Kidney-Metabolic (CKM) careOTHER

Participants will be referred to a nephrologist and receive a structured Cardio-Kidney-Metabolic (CKM) care strategy that includes iterative assessment of kidney and cardiovascular risk, early shared decision-making regarding guideline-directed medical therapies (RASi, SGLT2i, nsMRA, and GLP-1 RA), and close monitoring of treatment implementation, tolerability, and adverse effects throughout the study follow-up period.

Standard care (Comparison arm)OTHER

Participants will receive standard nephrology care according to routine clinical practice. Medication initiation and adjustment will be based on clinician judgment and relevant clinical parameters, with treatments introduced incrementally as part of usual care.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria 1. Age ≥ 18 years 2. T2DM 3. CKD (eGFR ≥ 25-60 mL/min/1.73 m² OR UACR ≥ 30 mg/g) - on screening labs 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 - within past 24 months), 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% within past 12 months 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. In the opinion of the investigator, currently treated with maximum tolerated dose of ≥3 medication classes:: RASi, SGLT2i, nsMRA or GLP1RA 8. Currently prescribed all 4 medication classes : RASi, SGLT2i, nsMRA or GLP1RA 9. Intolerance or allergy to any of RASi, SGLT2i, nsMRA or GLP1RA 10. Known Heart Failure with Reduced Ejection Fraction (HFrEF) 11. Current pregnancy, lactation or women of childbearing potential, unless using highly effective contraception

Outcomes

Primary Outcomes

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.

Time frame: 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.

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

Secondary Outcomes

Declined/ Unable to Receive Treatment - RASi

Percentage of participants in the intervention group who were recommended a RASi prescription and did not receive treatment for any reason. Participants meeting any of the following criteria are counted toward this single percentage: * Declined due to patient preference * Unable to obtain due to access barriers * Not initiated or titrated to avoid anticipated side effects Unit of Measure: Percent (%)

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

Declined or Unable to Receive Treatment- SGLT2i

Percentage of participants in the intervention group who were recommended a SGLT2i prescription and did not receive treatment for any reason. Participants meeting any of the following criteria are counted toward this single percentage: * Declined due to patient preference * Unable to obtain due to access barriers * Not initiated or titrated to avoid anticipated side effects Unit of Measure: Percent (%)

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

Declined or Unable to Receive Treatment - nsMRA

Percentage of participants in the intervention group who were recommended an nsMRA prescription and did not receive treatment for any reason. Participants meeting any of the following criteria are counted toward this single percentage: * Declined due to patient preference * Unable to obtain due to access barriers * Not initiated or titrated to avoid anticipated side effects Unit of Measure: Percent (%)

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

Declined or Unable to Receive Treatment - GLP1RA

Percentage of participants in the intervention group who were recommended an GLP1RA prescription and did not receive treatment for any reason. Participants meeting any of the following criteria are counted toward this single percentage: * Declined due to patient preference * Unable to obtain due to access barriers * Not initiated or titrated to avoid anticipated side effects Unit of Measure: Percent (%)

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

Loss to follow-up

Percentage of participants who are lost to follow-up from baseline through 12 months post-randomization. The target for loss to follow-up is \<10% over the duration of the study. Unit of Measure: Percent (%)

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

BMI

Change in body mass index (BMI) from baseline to 12 months. Calculated as 12-month value minus baseline value. Unit of Measure: kg/m²

Time frame: Baseline and 12 months post-randomization (±45-day visit window)

Waist circumference

Change in waist circumference from baseline to 12 months. Calculated as 12-month value minus baseline value. Unit of Measure: cm

Time frame: Baseline and 12 months post-randomization (±45-day visit window)

Hip circumference

Change in hip circumference from baseline to 12 months. Calculated as 12-month value minus baseline value. Unit of Measure: cm

Time frame: Baseline and 12 months post-randomization (±45-day visit window)

Waist-to-hip ratio

Change in waist-to-hip ratio from baseline to 12 months. Calculated as 12-month value minus baseline value. Unit of Measure: Ratio (unitless)

Time frame: Baseline and 12 months post-randomization (±45-day visit window)

Blood pressure

Change in systolic and diastolic blood pressure from baseline to 12 months. Calculated as 12-month value minus baseline value. Unit of Measure: mmHg

Time frame: Baseline and 12 months post-randomization (±45-day visit window)

Change in Urine Albumin-to-Creatinine Ratio (UACR)

Change in UACR from baseline to 12 months. Change will be calculated as 12-month value minus baseline value. Unit of Measure: mg/g

Time frame: Baseline and 12 months post-randomization (±45-day visit window)

Change in Estimated Glomerular Filtration Rate (eGFR)

Change in eGFR from baseline to 12 months. Change will be calculated as the 12-month value minus the baseline value.

Time frame: 12 months post-randomization (visit window ±45 days).

All-cause mortality

Death from any cause occurring from baseline to 12 months post-randomization. Unit of Measure: Number of participants

Time frame: Baseline to 12 months post-randomization (±45-day visit window)

Hospitalization for myocardial infarction

Any hospitalization for myocardial infarction occurring from baseline to 12 months post-randomization. Both incident and recurrent events will be captured. Unit of Measure: Number of participants

Time frame: Baseline to 12 months post-randomization (±45-day visit window)

Hospitalization for stroke

Any hospitalization for stroke occurring from baseline to 12 months post-randomization. Both incident and recurrent events will be captured. Unit of Measure: Number of participants

Time frame: Baseline to 12 months post-randomization (±45-day visit window)

Hospitalization for heart failure

Any hospitalization for heart failure occurring from baseline to 12 months post-randomization. Both incident and recurrent events will be captured. Unit of Measure: Number of participants

Time frame: Baseline to 12 months post-randomization (±45-day visit window)

All-cause hospitalization

Any hospitalization for any cause occurring from randomization to 12 months post-randomization. Ascertainment via Connecting Ontario administrative health data. Unit of Measure: Number of participants

Time frame: From randomization through 12 months post-randomization (visit windows ±45 days)

Hospitalization for diabetic ketoacidosis (DKA)

Any hospitalization for DKA occurring from randomization to 12 months post-randomization. Ascertainment via Connecting Ontario administrative health data. Unit of Measure: Number of participants

Time frame: From randomization through 12 months post-randomization (visit windows ±45 days)

Hyperkalemia requiring medication discontinuation or dose reduction

Occurrence of hyperkalemia leading to discontinuation or dose reduction of study medications (RASi, SGLT2i, nsMRA, GLP1RA) from randomization to 12 months post-randomization. Ascertainment via review of clinic notes and medication records. Unit of Measure: Number of participants

Time frame: From randomization through 12 months post-randomization (visit windows ±45 days)

eGFR dip requiring medication discontinuation or dose reduction

Occurrence of an eGFR decline requiring discontinuation or dose reduction of study medications from randomization to 12 months post-randomization. Ascertainment via review of clinic notes and medication records. Unit of Measure: Number of participants

Time frame: From randomization through 12 months post-randomization (visit windows ±45 days)

Symptomatic hypotension requiring medication discontinuation or dose reduction

Occurrence of symptomatic hypotension (SBP \<90 mmHg) leading to discontinuation or dose reduction of study medications from randomization to 12 months post-randomization. Ascertainment via review of clinic notes and medication records. Unit of Measure: Number of participants

Time frame: From randomization through 12 months post-randomization (visit windows ±45 days)

All-cause medication discontinuation

Discontinuation of any study medication for any reason from randomization to 12 months post-randomization. Ascertainment via review of clinic notes and medication records. Unit of Measure: Number of participants

Time frame: From randomization through 12 months post-randomization (visit windows ±45 days)

Medication Prescription

a) % of participants prescribed maximum indicated dose of RASi

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

Medication Prescription

b) % of participants prescribed maximum indicated dose of SGLT2i

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

Medication Prescription

c) % of participants prescribed maximum indicated dose of nsMRA

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

Medication Prescription

d) % of participants prescribed maximum indicated dose of GLP1RA (oral)

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

Medication Prescription

e) % of participants prescribed maximum indicated dose of GLP1RA (subcutaneous)

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

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts