Effects and Safety of Diabetic GUideline Algorithm Implementation Performed by Primary Care Physicians in the Community

Study Overview
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Brief Summary
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The Effects and Safety of Diabetic GUideline Algorithm Implementation in the Community (GUARD-Community) study is a 2-arm, cluster-randomized control trial to evaluate the effect and safety of guideline algorithm intervention performed by primary care physicians on cardiovascular and renal outcomes in elderly patients with high risk in community.

Detailed Description
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Diabetes is an important public health concern. Elderly diabetic patients are characterized by a long duration and complications, including chronic kidney disease and/or cardiovascular disease. In the past 30 years, the guidelines of CDS, EASD or ADA have been frequently updated. The latest guideline on pharmacological algorithm recommend that patients with cardiovascular, renal disease or very high/high CV risk patients should be treated with anti-diabetic drugs presenting target organ protection, including SGLT2i and GLP1RA. And the guideline recommend comprehensive control of the cardiovascular risk factors, such as hypertension and dyslipidemia. This GUARD-Community study is a community based cluster-randomized controlled trial and will enroll 5600 or more participants in more than 120 clusters aged ≥ 65 years with T2DM and complicated with high/very high cardiovascular risk factors . The trial will evaluate the the effects and safety of intensive Guideline algorithm implementation on CVD and renal outcomes. The primary hypothesis is that guideline algorithm intervention implemented by primary care physicians will significantly reduce the risk of 4-point MACE (comprised of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or hospitalization of heart failure) rates. In Phase 1 study, the control of blood sugar, blood pressure and lipids will be evaluated at 18 months after intervention. In Phase 2 study, the CVD and renal outcomes will be evaluated at 3 years. The study will last for 4 years.

Official Title
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Effects and Safety of GUideline Algorithm Based Intervention on CaRdiovascular and Renal Outcomes in Elderly Diabetic Patients With High Cardiovascular Risk in the Community- A Cluster Randomized Controlled Trial (GUARD-Community Study)

Conditions
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Type 2 Diabetes, Cardiovascular Complication, Diabetic Kidney Disease

Intervention / Treatment
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* Other: Intensive guideline algorithm implementation
* Other: Conventional guideline algorithm implementation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ①Males or females aged 65 and above (≥65) receive treatment from the local community health service center; ②Diagnosed type 2 diabetes (ADA criteria): A. Typical symptoms of diabetes + random blood sugar ≥ 11.1mmol/L; B. Fasting blood glucose (FPG) ≥ 7.0mmol/L (fasting blood glucose is defined as no caloric intake within 8 hours); C. Oral glucose tolerance test 2h blood glucose (OGTT) ≥ 11.1mmol/L (2h after meal); D. have been treated with antidiabetic drugs; Each blood sugar test must be repeated to confirm the diagnosis; ③Complicated with chronic kidney disease and/or very high/high risk of cardiovascular disease, meet any one of the following: A. ASCVD, including coronary heart disease, cerebral infarction, peripheral vascular disease; B. Or target organ damage (albuminuria, renal impairment with eGFR ≥ 30 ml/min/1.73m2, left ventricular hypertrophy or retinopathy); C. ≥ 3 major risk factors (age ≥ 65 years old, hypertension, dyslipidemia, smoking, obesity ); D. Diabetes duration ≥ 10 years, with any one traditional cardiovascular risk factor such as advanced age, obesity, smoking, sedentary, family history of cardiovascular disease, hypertension, abnormal lipid metabolism. Exclusion Criteria: ①Pregnant women or women planning to become pregnant; ②eGFR<30 mL/min/1.73m2 (CKD-EPI formula); ③Patient cannot be followed up for 36 months (due to health condition or migration); ④Unwilling or unable to sign the informed consent; ⑤Type 1 diabetes;

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Guideline based comprehensive management on the diabetic patients. In brief, SGLT2i or GLP-1RA will be used in priority in elderly diabetic patients with very high/high CV risk, and blood pressure controlled under 130/80mmHg， LDL-c<1.8mmol/L in the very high-risk patients or <2.6mmol/L in the high risk patients according to ESC/EASD guidelines.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensive guideline algorithm implementation<br>SGLT2i or GLP-1RA recommended in priority in subjects at very high/high CV risk. The targets of intervention will be achieved at HbA1C <7%, blood pressure <130/80mmHg， LDL-c<1.8mmol/L at very high CV risk or <2.6mmol/L at high CV risk patients, antiplatelet as secondary prevention of ASCVD. | Other: Intensive guideline algorithm implementation<br>* Diabetes guideline pharmacological algorithm will be implemented by primary care physicians in community. In brief, SGLT2i or GLP-1RA will be recommended to control blood glucose in priority when subjects at very high/high CV risk and meet the target HbA1C<7%, control blood pressure <130/80mmHg， LDL-c<1.8mmol/L at very high CV risk patients or <2.6mmol/L at high CV risk patients, and antiplatelet as secondary prevention of ASCVD.<br>|
| Active Comparator: Conventional guideline algorithm implementation<br>Treatment based on the current approaches implemented by local physicians(primary care physicians). Guideline based education and consults will be conducted to primary care physicians. | Other: Conventional guideline algorithm implementation<br>* The guideline intervention is based the guidance which the local physicians followed through self learning and education. The management of diabetes paitients will be decided by local physicians.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome of Phase 1: Comprehensive management effect of various cardiovascular risk factors in T2D，meeting control targets for a combination of A1c, BP, LDL-C. | The proportion of participants with HbA1C<7.0%, blood pressure< 130/80 mm Hg，LDL-c<1.8mmol/L at very high CV risk or <2.6mmol/L at high CV risk. | 18 months since randomization | 
| Primary Outcome of Phase 2: Composite of 3P MACE and hospitalization for heart failure. | Time to occurrence of cardiovascular and cerebrovascular death, non-fatal myocardial infarction, non-fatal Stroke, hospitalization for heart failure. | 3 years since randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Outcome of Phase 1: Glycemic control rate | The proportion of participants with tight glucose control, targeting HbA1c <7.0% | 18 months since randomization | 
| Secondary Outcome of Phase 1: Mean HbA1C changes | Mean HbA1C changes of participants | 18 months since randomization | 
| Secondary Outcome of Phase 1: Mean systolic and diastolic pressure changes | Mean systolic and diastolic pressure changes of participants | 18 months since randomization | 
| Secondary Outcome of Phase 1: Mean LDL-c changes | Mean LDL-c changes of participants | 18 months since randomization | 
| Secondary Outcome of Phase 1: Adherence to guideline algorithm medication recommendation rate | Use electronic medical recorded prescription and questionnaires to assess the proportion of participants who adhere to guideline recommended medication | 18 months since randomization | 
| Secondary Outcome of Phase 2: Incident or worsening nephropathy | Time to composite of incident macroalbuminuria (UACR >300 mg/g), a sustained decline in eGFR (decrease in the eGFR of 30% or more to a value of less than 60 when baseline ≥60ml per minute per 1.73 m2, decrease in the eGFR of 50% or more when baseline <60ml per minute per 1.73 m2)from baseline, or chronic renal replacement therapy, or renal death. | 3 years since randomization | 
| Secondary Outcome of Phase 2: Cardiorenal composite endpoint | Time to eGFR (CKD-EPI formula) decrease, renal replacement therapy, renal or cardiovascular death | 3 years since randomization | 
| Secondary Outcome of Phase 2: 3P MACE | Time to events occurence: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke | 3 years since randomization | 
| Secondary Outcome of Phase 2: New onset of macroalbuminuria. | Time to UACR>300mg/g | 3 years since randomization | 
| Secondary Outcome of Phase 2: Changes of myocardial ischemia in electrocardiogram (ECG) | Participants number of ECG ischemia demonstration occurence: ST-T segment depression more than 0.1mv in two adjacent leads of ECG compared with baseline, poor R wave progression. | 3 years since randomization | 
| Secondary Outcome of Phase 2: New onset of albuminuria | Time to UACR increase from <30mg/g to ≥30mg/g | 3 years since randomization | 
| Secondary Outcome of Phase 2: Albuminuria progression | Time to albuminuria progression: UACR increased by ≥30% and grade progression (ie, from normal to micro or macro, or from micro to macro) | 3 years since randomization | 
| Secondary Outcome of Phase 2: Albuminuria regression | Time to albuminuria regression: UACR grade regression(ie, from macro to micro or normal, or from micro to normal), and the UACR value decreases by more than or equal to 30% | 3 years since randomization | 
| Secondary Outcome of Phase 2: Changes in the ratio of patients with normal or abnormal urine protein at the end of the study | Rate change of normal or abnormal UACR. Normal means UACR<30mg/g. Abnormal means UACR≥30mg/g | 3 years since randomization | 
| Secondary Outcome of Phase 2: Slope of eGFR decline | Decrease of the eGFR over time | 3 years since randomization | 
| Secondary Outcome of Phase 2: Retinopathy changes | Occurrence or regression of retinopathy(ETDRS-DRSS) | 3 years since randomization | 
| Secondary Outcome of Phase 2: Body weight change | Absolute weight change and the percentage change of body weight | 3 years since randomization | 
| Secondary Outcome of Phase 2: Changes of fatty liver prevalence | Rate change of fatty liver. | 3 years since randomization | 
| Secondary Outcome of Phase 2: Changes in beta-cell function | Absolute change assessed by HOMA2-%β method | 3 years since randomization | 
| Secondary Outcome of Phase 2: Changes in cognitive function | Improvement or progression of cognitive function: The Mini-CogTM scale | 3 years since randomization | 
| Secondary Outcome of Phase 2: The FRAIL scale | Changes of the simple frailty questionnaire score | 3 years since randomization | 
| Secondary Outcome of Phase 2: All-cause death | Time to the death due to any cause | 3 years since randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes implementation study, Diabetes guideline algorithm, Cardiovascular disease, Chronic kidney disease