The Cardio-Metabolic Clinic

Background:

Despite improved treatment options, cardiovascular disease remains the leading cause of illness and death among patients with type 2 diabetes. It is crucial to recognize that managing diabetes involves more than just controlling blood sugar levels; preventing and treating cardiovascular disease is of significant importance. Lifestyle changes have been proven to have a substantial impact on cardiovascular health. Additionally, remarkable advancements in treatment options with cardiovascular protective effects have occurred over the past five years. Nevertheless, the traditional healthcare system primarily focuses on managing individual diseases, often leading to fragmented care for patients with type 2 diabetes. This fragmented approach often results in inadequate treatment, higher costs, and worse outcomes for cardiovascular disease. To address these challenges, our goal is to establish a Cardio-Metabolic Clinic that adopts a multidisciplinary approach to optimize diabetes management. The clinic will place special emphasis on implementing measures to protect the cardiovascular system and ensure comprehensive care for the patients. By bridging the gap between diabetes management and cardiovascular health, the aim is to enhance cardiovascular outcomes for patients with type 2 diabetes.

Organization in the Cardio-Metabolic Clinic:

The Cardio-Metabolic Clinic, structured on a cost-effective model, operates through a three-layered system centered on the patient. The innermost layer involves medical students or specialized cardio-metabolic nurses who maintain the daily contact with the patients. Patient medical history and baseline visit data are recorded in the Electronic Case-Report Form (Redcap). Upon randomization to the intervention arm, a decision-making algorithm in the Redcap-system is activated, ensuring that patients receive optimal and tailored medical treatment in accordance with the latest guidelines for diabetes management. The second layer includes a cardiologist who, in collaboration with the medical students or cardio-metabolic nurses, reviews the patients' risk profiles and algorithm-recommended treatments. If further counselling is needed for patient management, the third layer, consisting of an endocrinologist, a nephrologist and a hepatologist, will be consulted. This multidisciplinary collaboration ensures the most optimal diabetes management, especially in challenging cases.

Objectives:

The objective of the ProtecT-2-D trial is to investigate whether a comprehensive care in a Cardio-Metabolic Clinic are superior to standard treatment in reducing cardiovascular morbidity and mortality.

Hypothesis:

In patients with type 2 diabetes and cardiovascular disease, a systematic, specialized multidisciplinary approach in a Cardio-Metabolic Clinic, will result in better management of diabetes and reduced cardiovascular morbidity and mortality.

Methods:

The ProtecT-2-D study is a prospective, randomized, controlled trial conducted at the Cardiovascular Research Unit in Svendborg Hospital, Denmark. The study population consists of patients with type 2 diabetes and established cardiovascular disease, referred from general practices or seen in the outpatient clinic of Cardiology or Endocrinology at Svendborg Hospital. Sixteen hundred patients are anticipated to take part in the study. Patients are randomized in a 2:1 ratio to either receive comprehensive care at the Cardio-Metabolic Clinic or standard treatment. All patients are invited to undergo a health examination at baseline. Subsequently, patients enrolled in the Cardio-Metabolic Clinic will undergo a thorough multidisciplinary evaluation, including an optimization of lifestyle factors and medical treatment of cardiovascular risk factors based on current treatment guidelines.

After a duration of 3 years, all patients will be invited for a follow-up health examination. Furthermore, complications related to diabetes or cardiovascular disease will be assessed through registry and journal audits after 5 and 10 years.

Outcomes:

The primary outcome of the ProtecT-2-D trial is to investigate whether comprehensive care in a Cardio-Metabolic Clinic is superior to standard treatment. This will be assessed by the time to first occurrence of any of the endpoints in this composite: Death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for HF.

Sample size estimation:

A reduction in the primary endpoint of 15 % is anticipated in patients assessed in the Cardio-Metabolic Clinic compared to standard treatment. With a power of 80% and an alpha value of 0.05, 1306 patients are needed, and a dropout rate of around 15-20% is anticipated; therefore, 1600 patients will have to be included in the study.

• Time to first occurrence of MACE, a composite endpoint consisting of: CV death, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for HF. [Срок оценки: From baseline to 10 years of follow-up]
• Time to occurrence of the individual component CV death [Срок оценки: From baseline to 5 and 10 years of follow-up]
• Time to occurrence of the individual component AMI. [Срок оценки: From baseline to 5 and 10 years of follow-up]
• Time to occurrence of the individual component non-fatal stroke. [Срок оценки: From baseline to 5 and 10 years of follow-up]
• Time to first occurrence of a composite heart failure endpoint consisting of: de novo HF and HF hospitalisation. [Срок оценки: From baseline to 5 and 10 years of follow-up]
• Number of overall symptom burden determined by summing the occurences of CV death, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for HF. [Срок оценки: From baseline to 5 and 10 years of follow-up]
• Change in diabetic retinopathy stage based on eye examination (fundoscopy) [Срок оценки: From baseline to 3 years of follow-up]
• Change in estimated Glomerular Filtration Rate (eGFR) [Срок оценки: From baseline to 3 years of follow-up]
• Change in urinary albumin-to-creatinine ratio (UACR) [Срок оценки: From baseline to 3 years of follow-up]
• Change in Chronic Kidney Disease (CKD) stage [Срок оценки: From baseline to 3 years of follow-up]
• Time to first occurrence of a composite CKD endpoint consisting of a decline in eGFR [mL/min/1.73 m²] of more than 50%, onset of end-stage kidney disease (dialysis, eGFR<15, kidney transplantation) or death from renal or CV causes [Срок оценки: From baseline to 3 years of follow-up]
• Change in fibrosis-4 (FIB-4) [Срок оценки: From baseline to 3 years of follow-up]