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| Name | Class |
|---|---|
| The Kidney Foundation of Canada | OTHER |
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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:
Usual Care Arm:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Comparison Arm | Active Comparator | Standard of care |
|
| Intervention arm | Experimental | CKM |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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:
Unit of Measure: Percent (%) |
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Inclusion Criteria
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Kristina Hyunjee Lee, M.Ed | Contact | 437-869-7138 | Gold-standard@sunnybrook.ca |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39142721 | Background | 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. | |
| 32116454 | Background | 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. |
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Individual participant data (IPD) collected during this study will not be shared.
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|
| 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. |
|
| 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:
Unit of Measure: Percent (%) | 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:
| 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:
| 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 (%) | 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 | 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 | 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 | 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) | 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 | 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 | 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. | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | From randomization through 12 months post-randomization (visit windows ±45 days) |
| 36356631 | Background | 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 Dec 3;400(10367):1938-1952. doi: 10.1016/S0140-6736(22)02076-1. Epub 2022 Nov 7. |
| 22945832 | Background | 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. |
| 7580713 | 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. doi: 10.1136/bmj.311.7013.1145. |
| 37939689 | 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. 2024;55(2):206-213. doi: 10.1159/000535094. Epub 2023 Nov 8. |
| 33873265 | 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. |
| 32926067 | 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. |
| 37517546 | 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. |
| 37429523 | 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. |
| 35812300 | 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 May 5;7(7):1463-1476. doi: 10.1016/j.ekir.2022.04.094. eCollection 2022 Jul. |
| 35700142 | Background | Green JB, Mottl AK, Bakris G, Heerspink HJL, Mann JFE, McGill JB, Nangaku M, Rossing P, Scott C, Gay A, Agarwal R. 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. doi: 10.1093/ndt/gfac198. |
| 38569821 | Background | Brahmbhatt DH, Ross HJ, O'Sullivan M, Artanian V, Mueller B, Runeckles K, Steve Fan CP, Rac VE, Seto E; Medly Titrate Study Team. 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):678-690. doi: 10.1016/j.jchf.2024.02.008. |
| 33264825 | Background | Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, Kolkhof P, Nowack C, Schloemer P, Joseph A, Filippatos G; FIDELIO-DKD Investigators. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020 Dec 3;383(23):2219-2229. doi: 10.1056/NEJMoa2025845. Epub 2020 Oct 23. |
| 30990260 | 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. |
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| 38991584 | Background | Apperloo EM, Neuen BL, Fletcher RA, Jongs N, Anker SD, Bhatt DL, Butler J, Cherney DZI, Herrington WG, Inzucchi SE, Jardine MJ, Liu CC, Mahaffey KW, McGuire DK, McMurray JJV, Neal B, Packer M, Perkovic V, Sabatine MS, Solomon SD, Staplin N, Szarek M, Vaduganathan M, Wanner C, Wheeler DC, Wiviott SD, Zannad F, Heerspink HJL. 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):545-557. doi: 10.1016/S2213-8587(24)00155-4. Epub 2024 Jul 8. |
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| 34426012 | 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. |
| ID | Term |
|---|---|
| D003928 | Diabetic Nephropathies |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D048909 | Diabetes Complications |
| D004700 | Endocrine System Diseases |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D052283 | Creatine Kinase, MM Form |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D003402 | Creatine Kinase |
| D017852 | Phosphotransferases (Nitrogenous Group Acceptor) |
| D010770 | Phosphotransferases |
| D014166 | Transferases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
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