Chronic Kidney Disease, Diabetic Kidney Disease (DKD), Type 2 Diabetes Mellitus (T2DM)
Conditions
Keywords
diabetes, diabetic kidney disease, cardiovascular risk, Cardio-Kidney-Metabolic (CKM) care, CKM Care, Guideline-Directed Medical Therapy
Brief summary
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.
Detailed description
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.
Interventions
OTHEREarly goal-directed Cardio-Kidney-Metabolic (CKM) care
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.
OTHERStandard care (Comparison arm)
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.
Sponsors
Sunnybrook Health Sciences Centre
The Kidney Foundation of Canada
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
SINGLE (Outcomes Assessor)
Masking description
This is an open-label study in which participants and treating clinicians are aware of treatment assignment. Outcome assessments will be performed by an independent adjudicator who is blinded to treatment allocation.
Intervention model description
Participants will be randomized 1:1 to early goal-directed CKM care or usual care. The study is designed to evaluate the feasibility and safety of implementing a structured CKM care strategy within routine nephrology practice.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of the pivotal Randomized Controlled Trial (RCT) | From consent through completion of screening procedures to randomization (maximum 60 days). | Percentage of consenting participants who are eligible and randomized. Feasibility is defined as ≥40% of consented and screened participants meeting criteria and being randomized. |
| Prescription and Adherence to Guideline-Directed Medical Therapy (GDMT) | 12 months after randomization (±45-day window). | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Declined/ Unable to Receive Treatment - RASi | Baseline to 12 months post-randomization (±45-day visit window). | 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 (%) |
| Medication Prescription | Baseline to 12 months post-randomization (±45-day visit window). | a) % of participants prescribed maximum indicated dose of RASi |
| Declined or Unable to Receive Treatment- SGLT2i | Baseline to 12 months post-randomization (±45-day visit window). | 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 (%) |
| Declined or Unable to Receive Treatment - nsMRA | Baseline to 12 months post-randomization (±45-day visit window). | 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 (%) |
| Declined or Unable to Receive Treatment - GLP1RA | Baseline to 12 months post-randomization (±45-day visit window). | 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 (%) |
| Loss to follow-up | Baseline to 12 months post-randomization (±45-day visit window). | 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 (%) |
| BMI | Baseline and 12 months post-randomization (±45-day visit window) | Change in body mass index (BMI) from baseline to 12 months. Calculated as 12-month value minus baseline value. Unit of Measure: kg/m² |
| Waist circumference | Baseline and 12 months post-randomization (±45-day visit window) | Change in waist circumference from baseline to 12 months. Calculated as 12-month value minus baseline value. Unit of Measure: cm |
| Hip circumference | Baseline and 12 months post-randomization (±45-day visit window) | Change in hip circumference from baseline to 12 months. Calculated as 12-month value minus baseline value. Unit of Measure: cm |
| Waist-to-hip ratio | Baseline and 12 months post-randomization (±45-day visit window) | Change in waist-to-hip ratio from baseline to 12 months. Calculated as 12-month value minus baseline value. Unit of Measure: Ratio (unitless) |
| Blood pressure | Baseline and 12 months post-randomization (±45-day visit window) | Change in systolic and diastolic blood pressure from baseline to 12 months. Calculated as 12-month value minus baseline value. Unit of Measure: mmHg |
| Change in Urine Albumin-to-Creatinine Ratio (UACR) | Baseline and 12 months post-randomization (±45-day visit window) | Change in UACR from baseline to 12 months. Change will be calculated as 12-month value minus baseline value. Unit of Measure: mg/g |
| Change in Estimated Glomerular Filtration Rate (eGFR) | 12 months post-randomization (visit window ±45 days). | Change in eGFR from baseline to 12 months. Change will be calculated as the 12-month value minus the baseline value. |
| All-cause mortality | Baseline to 12 months post-randomization (±45-day visit window) | Death from any cause occurring from baseline to 12 months post-randomization. Unit of Measure: Number of participants |
| Hospitalization for myocardial infarction | Baseline to 12 months post-randomization (±45-day visit window) | 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 |
| Hospitalization for stroke | Baseline to 12 months post-randomization (±45-day visit window) | 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 |
| Hospitalization for heart failure | Baseline to 12 months post-randomization (±45-day visit window) | 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 |
| All-cause hospitalization | From randomization through 12 months post-randomization (visit windows ±45 days) | 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 |
| Hospitalization for diabetic ketoacidosis (DKA) | From randomization through 12 months post-randomization (visit windows ±45 days) | 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 |
| Hyperkalemia requiring medication discontinuation or dose reduction | From randomization through 12 months post-randomization (visit windows ±45 days) | 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 |
| eGFR dip requiring medication discontinuation or dose reduction | From randomization through 12 months post-randomization (visit windows ±45 days) | 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 |
| Symptomatic hypotension requiring medication discontinuation or dose reduction | From randomization through 12 months post-randomization (visit windows ±45 days) | 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 |
| All-cause medication discontinuation | From randomization through 12 months post-randomization (visit windows ±45 days) | 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 |
Countries
Canada
Contacts
CONTACTAyodele Odutayo, Doctor
CONTACTGOLD STANDARD Coordinating Centre
Outcome results
None listed