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

Sponsor

Shanghai Zhongshan Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05349955

Collaborator

(none)

5,600

Enrollment

Arms

48.7

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Cardiovascular Complication Diabetic Kidney Disease	Other: Intensive guideline algorithm implementation Other: Conventional guideline algorithm implementation	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

5600 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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 (Outcomes Assessor)

Masking Description:

Outcome Assessment Committee members will be blinded to outcome assignment.

Primary Purpose:

Treatment

Official Title:

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)

Anticipated Study Start Date :

Aug 10, 2022

Anticipated Primary Completion Date :

Aug 30, 2026

Anticipated Study Completion Date :

Aug 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intensive guideline algorithm implementation 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 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.
Active Comparator: Conventional guideline algorithm implementation 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 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.

Arm

Intervention/Treatment

Experimental: Intensive guideline algorithm implementation

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

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.

Active Comparator: Conventional guideline algorithm implementation

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

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.

Outcome Measures

Primary Outcome Measures

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. [18 months since randomization]
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.
Primary Outcome of Phase 2: Composite of 3P MACE and hospitalization for heart failure. [3 years since randomization]
Time to occurrence of cardiovascular and cerebrovascular death, non-fatal myocardial infarction, non-fatal Stroke, hospitalization for heart failure.

Secondary Outcome Measures

Secondary Outcome of Phase 1: Glycemic control rate [18 months since randomization]
The proportion of participants with tight glucose control, targeting HbA1c <7.0%
Secondary Outcome of Phase 1: Mean HbA1C changes [18 months since randomization]
Mean HbA1C changes of participants
Secondary Outcome of Phase 1: Mean systolic and diastolic pressure changes [18 months since randomization]
Mean systolic and diastolic pressure changes of participants
Secondary Outcome of Phase 1: Mean LDL-c changes [18 months since randomization]
Mean LDL-c changes of participants
Secondary Outcome of Phase 1: Adherence to guideline algorithm medication recommendation rate [18 months since randomization]
Use electronic medical recorded prescription and questionnaires to assess the proportion of participants who adhere to guideline recommended medication
Secondary Outcome of Phase 2: Incident or worsening nephropathy [3 years since randomization]
Time to composite of incident macroalbuminuria (UACR >300 mg/g), a sustained decline in eGFR of 40% or more from baseline, or chronic renal replacement therapy, or renal death.
Secondary Outcome of Phase 2: Cardiorenal composite endpoint [3 years since randomization]
Time to eGFR (MDRD formula) decrease ≥40%, renal replacement therapy, renal or cardiovascular death
Secondary Outcome of Phase 2: 3P MACE [3 years since randomization]
Time to events occurence: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke
Secondary Outcome of Phase 2: New onset of macroalbuminuria. [3 years since randomization]
Time to UACR>300mg/g
Secondary Outcome of Phase 2: Changes of myocardial ischemia in electrocardiogram (ECG) [3 years since randomization]
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.
Secondary Outcome of Phase 2: New onset of albuminuria [3 years since randomization]
Time to UACR increase from <30mg/g to ≥30mg/g
Secondary Outcome of Phase 2: Albuminuria progression [3 years since randomization]
Time to albuminuria progression: UACR increased by ≥30% and grade progression (ie, from normal to micro or macro, or from micro to macro)
Secondary Outcome of Phase 2: Albuminuria regression [3 years since randomization]
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%
Secondary Outcome of Phase 2: Changes in the ratio of patients with normal or abnormal urine protein at the end of the study [3 years since randomization]
Rate change of normal or abnormal UACR. Normal means UACR<30mg/g. Abnormal means UACR≥30mg/g
Secondary Outcome of Phase 2: Slope of eGFR decline [3 years since randomization]
Decrease of the eGFR over time
Secondary Outcome of Phase 2: Retinopathy changes [3 years since randomization]
Occurrence or regression of retinopathy(ETDRS-DRSS)
Secondary Outcome of Phase 2: Body weight change [3 years since randomization]
Absolute weight change and the percentage change of body weight
Secondary Outcome of Phase 2: Changes of fatty liver prevalence [3 years since randomization]
Rate change of fatty liver.
Secondary Outcome of Phase 2: Changes in beta-cell function [3 years since randomization]
Absolute change assessed by HOMA2-%β method
Secondary Outcome of Phase 2: Changes in cognitive function [3 years since randomization]
Improvement or progression of cognitive function: The Mini-CogTM scale
Secondary Outcome of Phase 2: The FRAIL scale [3 years since randomization]
Changes of the simple frailty questionnaire score
Secondary Outcome of Phase 2: All-cause death [3 years since randomization]
Time to the death due to any cause

Other Outcome Measures

Health Economics Indicators [3 years since randomization]
Cost-effectiveness analysis： quantification of Incremental Cost Ratio Life Cycle (ICER) and Quality Adjusted Years (QALYs)
Changes in cardiovascular risk indicators [3 years since randomization]
Framingham score
Serology and urine testing [3 years since randomization]
Biomarkers associated with diagnosis or prognosis: using "omics" screening.
Genomics testing [3 years since randomization]
Gene polymorphism testing for drug response or prognosis: using genome-wide association study(GWAS) screening.
The time rate of glycemic target range [3 years since randomization]
Continous glucose monitor detection

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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):
1. Typical symptoms of diabetes + random blood sugar ≥ 11.1mmol/L;
1. Fasting blood glucose (FPG) ≥ 7.0mmol/L (fasting blood glucose is defined as no caloric intake within 8 hours);
1. Oral glucose tolerance test 2h blood glucose (OGTT) ≥ 11.1mmol/L (2h after meal);
1. 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:
1. ASCVD, including coronary heart disease, cerebral infarction, peripheral vascular disease;
1. Or target organ damage (albuminuria, renal impairment with eGFR ≥ 30 ml/min/1.73m2, left ventricular hypertrophy or retinopathy);
1. ≥ 3 major risk factors (age ≥ 65 years old, hypertension, dyslipidemia, smoking, obesity BMI ≥ 28kg/m2);
1. 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 (MDRD 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;