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

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)

Overview

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

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.

Interventions

• 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.
• 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.

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. [Time frame: 18 months since randomization]
• Primary Outcome of Phase 2: Composite of 3P MACE and hospitalization for heart failure. [Time frame: 3 years since randomization]

Secondary outcome measures (12)

• Secondary Outcome of Phase 1: Glycemic control rate [Time frame: 18 months since randomization]
• Secondary Outcome of Phase 1: Mean HbA1C changes [Time frame: 18 months since randomization]
• Secondary Outcome of Phase 1: Mean systolic and diastolic pressure changes [Time frame: 18 months since randomization]
• Secondary Outcome of Phase 1: Mean LDL-c changes [Time frame: 18 months since randomization]
• Secondary Outcome of Phase 1: Adherence to guideline algorithm medication recommendation rate [Time frame: 18 months since randomization]
• Secondary Outcome of Phase 2: Incident or worsening nephropathy [Time frame: 3 years since randomization]
• Secondary Outcome of Phase 2: Cardiorenal composite endpoint [Time frame: 3 years since randomization]
• Secondary Outcome of Phase 2: 3P MACE [Time frame: 3 years since randomization]
• Secondary Outcome of Phase 2: New onset of macroalbuminuria. [Time frame: 3 years since randomization]
• Secondary Outcome of Phase 2: Changes of myocardial ischemia in electrocardiogram (ECG) [Time frame: 3 years since randomization]
• Secondary Outcome of Phase 2: New onset of albuminuria [Time frame: 3 years since randomization]
• Secondary Outcome of Phase 2: Albuminuria progression [Time frame: 3 years since randomization]

Eligibility criteria

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;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 13 centers

• Xiangcheng Second People's Hospital — Suzhou
• Caohu Community Healthcare Center — Suzhou
• Huangqiao Community Healthcare Center — Suzhou
• Xiangcheng People's Hospital. — Suzhou
• Yuanhe Community Healthcare Center — Suzhou
• Xiangcheng Third People's Hospital — Suzhou
• Taiping Community Healthcare Center — Suzhou
• Yangchenghu People's Hospital — Suzhou
• … and 5 more centers

Publications

• Gu TW, Zhu DL. [Interpretation of treatment part of national guideline for the prevention and control of diabetes in primary care (2018)]. Zhonghua Nei Ke Za Zhi. 2019 Jul 1;58(7):538-540. doi: 10.3760/cma.j.issn.0578-1426.2019.07.011. Chinese. PMID 31269573
• Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):837-53. PMID 9742976
• Gross JL, de Azevedo MJ, Silveiro SP, Canani LH, Caramori ML, Zelmanovitz T. Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care. 2005 Jan;28(1):164-76. doi: 10.2337/diacare.28.1.164. PMID 15616252
• Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17. PMID 26378978
• Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Silverman MG, Zelniker TA, Kuder JF, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Ruff CT, Gause-Nilsson IAM, Fredriksson M, Johansson PA, Langkilde AM, Sabatine MS; DECLARE-TIMI 58 Investigators. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019 Jan 24;380(4):347-357. doi: 10.1056/NEJMoa1812389. PMID 30415602
• Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR; CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Aug 17;377(7):644-657. doi: 10.1056/NEJMoa1611925. Epub 2017 Jun 12. PMID 28605608
• Bhatt DL, Szarek M, Steg PG, Cannon CP, Leiter LA, McGuire DK, Lewis JB, Riddle MC, Voors AA, Metra M, Lund LH, Komajda M, Testani JM, Wilcox CS, Ponikowski P, Lopes RD, Verma S, Lapuerta P, Pitt B; SOLOIST-WHF Trial Investigators. Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. N Engl J Med. 2021 Jan 14;384(2):117-128. doi: 10.1056/NEJMoa2030183. Epub 2020 Nov 16. PMID 33200892
• Heerspink HJL, Stefansson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjostrom CD, Toto RD, Langkilde AM, Wheeler DC; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24. PMID 32970396

Identifiers

NCT: NCT05349955 · ZSE 20220401

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗