Diabetes Complication Control in Community Clinics (D4C) Trial

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 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 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 11,780 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 310 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 the
difference in the combined changes in HbA1C, SBP, and LDL-cholesterol levels between
intervention and control groups, simultaneously modeled using a scaled marginal model which
allows estimation of a single overall treatment effect. 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 individually; (2) estimated 10-year risk of CVD; (3) the
proportion of participants with HbA1C <7% (or <7.5% if with clinical CVD), BP <140/90 mm Hg,
and LDL-cholesterol <100 mg/dL; (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 3.6% reduction in the combined changes in 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.

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