Clinical trial NCT06203860: The Cardio-Metabolic Clinic
Official title: Cardiovascular Protection in Patients With Type 2 Diabetes and Established Heart or Vascular Disease - The Cardio-Metabolic Clinic
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Cardiovascular Diseases
Keywords: Cardiovascular death
Heart attack
Stroke
Heart failure
Diabetic microvascular complications
Diabetic macrovascular complications
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
First posted: 2024-01-12
Enrollment: 1600
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization in the ProtecT-2-D is carried out using the Randomization Module in the electronic Case Report Form (e-CRF) system, REDCap. To ensure concealed allocation the allocation table is created by a REDCap team member, who is independent of the ProtecT-2-D project staff.

Participants will be randomized to either the Cardio-Metabolic Clinic or usual care in a ratio of 2:1

1. Cardio-Metabolic Clinic
2. Usual care
Primary purpose: PREVENTION

Brief summary: This study aims to investigate whether a Cardio-Metabolic Clinic can protect the cardiovascular health of patients with both diabetes and cardiovascular disease.

* At the Cardio-Metabolic Clinic, patients will receive a specialized and comprehensive care. This includes applying a systematic approach, considering their whole health based on the latest knowledge in the field, and administering aggressive treatment with heart protective medications.
* The ProtecT-2-D trial will compare the effects of care at the Cardio-Metabolic Clinic to usual care to see if there are any differences in cardiovascular illness and death.

Detailed description: 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.

Eligibility criteria: Inclusion:

* \>18 years
* Capable of giving written informed consent
* Established diagnosis of T2D
* Having established heart or vascular disease defined as either:
* Atherosclerotic disease defined as:

  1. Prior acute coronary syndrome (ACS).
  2. Chronic coronary syndrome defined as the combination of: Angina pectoris AND coronary atherosclerosis assessed with either Coronary CT angiography (CTA) or Myocardial-scintigraphy (MPI) or Coronary angiography (CAG) AND treatment with statins and/or acetylsalicylic acid.
  3. Stroke.
  4. Peripheral arterial disease (PAD) defined as: Claudication intermittence in combination with pathological ABI AND/OR vascular PAD surgery AND/OR ischemic amputation.
  5. Ischemic heart disease defined by one of the following criteria: a) Myocardial-scintigraphy: \>10% reversibility OR b) Coronary CT angiography: Coronary Artery Calcium (CAC)-score \>100.
* Heart failure (HF): HF with reduced ejection fraction (HFrEF), HF with Mildly reduced ejection fraction (HFmrEF), HF with preserved ejection fraction (HFpEF)
* Atrial fibrillation and/or flutter, including paroxysmal, persistent and chronic disease
* Valvular heart disease (which requires control in outpatient clinic of cardiology), such as aortic valve stenosis, mitral valve insufficiency, and patients with aortic dilatation
* Hypertension treated with at least three antihypertensive drugs

Exclusion:

* Life expectancy less than 5 years for any reason
* Type 1 Diabetes Mellitus
* Participation in another clinical trial with an investigational product or device that could interfere with the primary and/or secondary endpoints of this study

Primary outcomes:
measure: Time to first occurrence of major adverse cardiovascular event (MACE), a composite endpoint consisting of: cardiovascular (CV) death, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for heart failure (HF).
timeFrame: From baseline to 5 years of follow-up
Secondary outcomes:
measure: Time to first occurrence of MACE, a composite endpoint consisting of: CV death, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for HF.
timeFrame: From baseline to 10 years of follow-up
measure: Time to occurrence of the individual component CV death
timeFrame: From baseline to 5 and 10 years of follow-up
measure: Time to occurrence of the individual component AMI.
timeFrame: From baseline to 5 and 10 years of follow-up
measure: Time to occurrence of the individual component non-fatal stroke.
timeFrame: From baseline to 5 and 10 years of follow-up
measure: Time to first occurrence of a composite heart failure endpoint consisting of: de novo HF and HF hospitalisation.
timeFrame: From baseline to 5 and 10 years of follow-up
measure: Number of overall symptom burden determined by summing the occurences of CV death, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for HF.
timeFrame: From baseline to 5 and 10 years of follow-up
measure: Change in diabetic retinopathy stage based on eye examination (fundoscopy)
timeFrame: From baseline to 3 years of follow-up
measure: Change in estimated Glomerular Filtration Rate (eGFR)
timeFrame: From baseline to 3 years of follow-up
measure: Change in urinary albumin-to-creatinine ratio (UACR)
timeFrame: From baseline to 3 years of follow-up
measure: Change in Chronic Kidney Disease (CKD) stage
timeFrame: From baseline to 3 years of follow-up
measure: 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
timeFrame: From baseline to 3 years of follow-up
measure: Change in fibrosis-4 (FIB-4)
timeFrame: From baseline to 3 years of follow-up
measure: Change in degree of liver fibrosis in high-risk individuals assessed through a Fibro-scan
timeFrame: From baseline to 3 years of follow-up
measure: Time to first occurrence of a composite macrovascular diabetic complications endpoint comprising new diagnosis of lower extremity arterial disease (LEAD), new/progression of foot ulcers, surgical procedures related to PAD, and coronary revascularisation
timeFrame: From baseline to 3 years of follow-up
measure: Change in ankle-brachial pressure index (ABI).
timeFrame: From baseline to 3 years of follow-up
measure: Change in protocol-driven medication
timeFrame: From baseline to 3 years of follow-up
measure: Change in symptoms as reported by patients using the Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: From baseline to 3 years of follow-up
measure: Net cost analysis of implementing a Cardio-Metabolic Clinic
timeFrame: From baseline to 5 and 10 years of follow-up
measure: Change in health outcomes measured by quality-adjusted life years (QALY)
timeFrame: From baseline to 5 and 10 years of follow-up
measure: Cost-effectiveness ratio of implementing a Cardio-Metabolic Clinic
timeFrame: From baseline to 5 and 10 years of follow-up
Other outcomes:
Locations:
city: Svendborg
country: Denmark
facility: Cardiovascular Research Unit, Odense University Hospital - Svendborg
state: South Denmark
Study officials:
affiliation: Cardiovascular Research Unit. Odense University Hospital, Svendborg
name: Soeren Auscher, M.D, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: