Diabetes Complication Control in Community Clinics (D4C) Trial (D4C)

The overall objective of the proposed cluster randomized trial is to test whether implementation of protocol-based integrated care will improve CVD risk factors (glycated hemoglobin [HbA1C], systolic blood pressure [SBP], and LDL-cholesterol) over 18 months and reduce major CVD events (non-fatal stroke, non-fatal myocardial infarction, hospitalized heart failure, and CVD mortality) over 3 years among patients with type 2 diabetes and additional CVD risk factors or clinical CVD compared to usual team-based care in community clinics in Xiamen, China.

Study Overview

• Status: Active, not recruiting
• Conditions: Hypertension; Cardiovascular Disease; Diabetes; Dyslipidemia
• Intervention / Treatment: Other: Protocol-based integrated care

Detailed Description

Diabetes has reached epidemic proportions in China. Most patients with diabetes have multiple uncontrolled cardiovascular disease (CVD) risk factors due to suboptimal care, especially in underserved populations. The overall objective of the proposed cluster randomized trial is to test whether implementation of protocol-based integrated care (team-based care with clinical decision support systems) will improve CVD risk factors (glycated hemoglobin [HbA1C], systolic blood pressure [SBP], and LDL-cholesterol) over 18 months and reduce major CVD events (non-fatal stroke, non-fatal myocardial infarction, hospitalized heart failure, and CVD mortality) over 3 years among patients with type 2 diabetes and additional CVD risk factors or clinical CVD compared to usual team-based care in community clinics in Xiamen, China. The protocol-based integrated care, which will provide a standardized, combined, multi-component intervention according to clinical guideline treatment algorithms for diabetes and comorbidities in community clinics, will be delivered by trained primary care physicians, health managers, and nurses supported by diabetes specialists. The proposed trial will recruit approximately 12,160 patients with diabetes and additional CVD risk factors or clinical CVD from 38 community-based primary care clinics (community health service centers) in Xiamen, China. Nineteen community clinics with approximately 320 participants each will be randomly assigned to the intervention group and 19 community clinics with similar participants to the control group matched by administrative district and socioeconomic status. The protocol-based integrated care intervention will last for 36 months. HbA1C, BP, LDL-cholesterol, other variables, and co-morbidities will be measured at baseline and follow-up visits at months 6, 12, 18, 24, 30 and 36. In phase 1 (during the first 18-month intervention), the primary outcome is reduction in HbA1c, BP, and LDL-cholesterol measured by differences in mean changes in HbA1c, LDL cholesterol, and systolic BP levels over 18 months simultaneously modeled for a single overall treatment effect and proportion of patients with controlled HbA1c, BP, and LDL-C at 18 months. In phase 2 (during the three-year intervention), the primary outcome is the difference in major CVD incidence (non-fatal stroke, non-fatal myocardial infarction, hospitalized heart failure, and CVD mortality) between intervention and control groups. The secondary outcomes include: (1) the net changes in HbA1C, SBP, and LDL-cholesterol; (2) estimated 10-year risk of CVD; (3) the proportion of participants with controlled HbA1C, systolic BP, and LDL-cholesterol; (4) health-related quality of life; and (5) cost-effectiveness of intervention over three years. The proposed trial is designed to provide 90% statistical power to detect a 5% increase in the combined control rate of HbA1C, SBP, and LDL-cholesterol levels in phase 1 and a 20% reduction in major CVD (non-fatal stroke, non-fatal myocardial infarction, hospitalized heart failure, and CVD mortality) in phase 2 at a significance level of 0.05 for a two-sided test. This will be the first randomized cluster trial to test the implementation of a protocol-based integrated care program on multiple CVD risk factors and CVD events in diabetes patients who receive care from community clinics in China. This implementation research project has a high impact in public health because it will generate urgently needed data on an effective, practical, and sustainable intervention program aimed at reducing the CVD burden among diabetes patients in middle- and low-income countries.

• Study Type: Interventional
• Enrollment (Actual): 11132
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Fujian
    • Xiamen, Fujian, China, 361003
      • Xiamen Diabetes Institute, Xiamen University
• United States
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men or women aged ≥50 years who received primary care from the participating community clinics
• Uncontrolled diabetes (HbA1C ≥7% or ≥7.5% if with clinical CVD) with at least one additional CVD risk factor (SBP ≥140 and/or DBP ≥90 mm Hg and/or LDL-cholesterol ≥100 mg/dL) or clinical ASCVD (acute coronary syndromes, ischemic stroke, transient ischemic attack, or peripheral artery disease)

Exclusion Criteria:

• Patients with NYHA class II-IV heart failure, or receiving hemodialysis, or with contraindications to metformin or statin treatments
• Women who are pregnant or plan to become pregnant
• Patients who cannot be followed for 36 months (due to a health situation or migration)
• Patients who are unwilling or unable to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Protocol-based Integrated Care; The protocol-based integrated care, which will provide a standardized, combined, multi-component intervention according to clinical guideline treatment algorithms for diabetes and comorbidities in community clinics, will be delivered by care team (trained primary care physicians, health managers, and nurses supported by diabetes specialists) and assisted by a clinical decision support systems.	Other: Protocol-based integrated care; The protocol-based integrated care, which will provide a standardized, combined, multi-component intervention according to clinical guideline treatment algorithms for diabetes and comorbidities in community clinics, will be delivered by trained primary care physicians, health managers, and nurses supported by diabetes specialists.
Active Comparator: Enhanced Control; A usual team-based care delivered by trained primary care physicians, health managers, and nurses supported by diabetes specialists.	Other: Protocol-based integrated care; The protocol-based integrated care, which will provide a standardized, combined, multi-component intervention according to clinical guideline treatment algorithms for diabetes and comorbidities in community clinics, will be delivered by trained primary care physicians, health managers, and nurses supported by diabetes specialists.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1C, SBP, and LDL between intervention and control groups, simultaneously modeled using a scaled marginal model which allows estimation of a single overall treatment effect and combined control rate of HbA1c, SBP, and LDL	For patients younger than 65 years, HbA1c ≤7.0% or ≤8.0% in those with complications; for patients 65 years or older, HbA1c ≤7.5% or HbA1c ≤8.5% in those with complications; LDL-cholesterol <100 mg/dL; and blood pressure <140/90 mm Hg	18 months
Incidence of composite major cardiovascular disease events	Non-fatal stroke, non-fatal myocardial infarction, hospitalized heart failure, and CVD mortality	Three years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1C	Net change in HbA1c or proportion of controlled HbA1c	18 months
SBP	Net change in SBP or proportion of controlled BP	18 months
LDL-cholesterol	Net change in LDL or controlled LDL	18 months
CVD risk score	10-year risk of CVD using ACC/AHA Risk Scores	18 months
Health-related quality of life: 12-item Short-Form Health Survey	Health-related quality of life by the 12-item Short-Form Health Survey	Three years
Cost-effectiveness	Incremental Cost-Effectiveness Ratio	Three years

Collaborators and Investigators

• Sponsor: Tulane University
• Collaborators: Xiamen University
• Investigators: Study Chair: Jiang He, MD, PhD, Tulane University

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2016
• Primary Completion (Estimated): December 30, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: July 6, 2016
• First Submitted That Met QC Criteria: July 13, 2016
• First Posted (Estimated): July 18, 2016

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Lipid Metabolism Disorders; Cardiovascular Diseases; Diabetes Mellitus; Dyslipidemias; Diabetes Complications
• Other Study ID Numbers: 889920-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO