Heart-Kidney-Diabetes Multidisciplinary Care MOdels for CardiovascuLar Health In Patients With Chronic Kidney DiSease and Diabetes: A PragmaTIC Cluster Randomized Controlled Trial (HOLISTIC)

Phase 4Not Yet RecruitingNCT07811427

Baim Institute for Clinical Research570 enrolled

Overview

Our overarching goal of this study is to provide rigorous evidence for using an accelerated risk-based approach to implementing guideline directed medical therapies (GDMT) using a multidisciplinary care model (MCM) versus a usual care model (UCM) to improve a composite GDMT score, reduce kidney disease and heart failure (HF) events, hospitalizations, and total healthcare costs for patients with type 2 diabetes (T2D) and CKD with high- to very-high Kidney Disease: Improving Global Outcomes (KDIGO) risk.

The study is designed to provide evidence for MCM versus UCM to improve a composite GDMT score, reduce major kidney and cardiovascular risks, reduce hospitalizations (and thereby healthcare costs), and improve QoL, for patients with T2D and high and very high KDIGO CKD risk. These Specific Aims address critical gaps including lack of patient access to subspecialists, PCC and patient inertia, and inadequate infrastructure to optimize nutrition. The MCM is designed to increase GDMT uptake across the health system, PCC, and patient domains. Outside the US, MCMs in patients with CKD and T2D have shown promise by reducing CKM risk factors, healthcare costs, subspecialty clinic visits, and hospitalizations. Given lack of patient access to subspecialists in the US,32 especially nephrologists, a specialist-dominant model for GDMT uptake and optimization may not be feasible in many health systems. Notably, PCCs are also in shortage by workforce capacity, and they have large patient panels, severe time constraints, and competing priorities. Therefore, maintaining vital PCC and patient relationships, while bringing a primary-care-based CKM pharmacist onboard with consulting subspecialists, is a way forward. HOLISTIC will answer a call for research on team-based primary care to alleviate physician shortages for under-served health needs such as T2D and CKD. This approach can also capitalize on successes pioneered by telehealth during the COVID-19 pandemic for complex chronic conditions by assisting PCCs through pharmacist led CMM. Finally, it allows a strategic re-purposing of existing resources (pharmacist clinicians) who can support PCCs and lead CMM and GDMT deployment in a risk-appropriate and timely fashion, to demonstrate value to this alternate model across optimal care delivery, clinical outcomes, cost savings/return on investment.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Provide written informed consent 2. Adults ≥18 years of age with T2D and CKD at high or very high KDIGO risk (Figure A1): eGFR 45-59 mL/min/1.73 m2 and UACR \>300 mg/g OR eGFR 30-44 mL/min/1.73 m2 and UACR \>30 mg/g OR any eGFR \<30 mL/min/1.73 m2. Exclusion Criteria: 1. Advanced HF on inotrope support or requiring left ventricular assist device support. 2. Chronic hemodialysis or peritoneal dialysis or kidney transplant 3. Life expectancy of \<1-year, and vulnerable populations such as pregnant women, incarcerated individuals, or those with active psychiatric illness. 4. Unreliable or non-compliant, including patients with known history of alcoholism, drug abuse, or serious psychiatric disorder; as well as patients unwilling to abide by the requirements of the protocol 5. Any condition that would interfere with the patient's ability to comply with study instructions, might confound the interpretation of the study, or put the patient at risk 6. Personnel, or any relative of personnel, of the Sponsor, the CRO, or the investigative site(s)

Outcomes

Primary Outcomes

Change in Composite Guideline-Directed Medical Therapy (GDMT) Score

Composite GDMT calculated from baseline to Month 12 across five pre-defined medication classes (RAS inhibitors, SGLT2 inhibitors, GLP-1 receptor antagonists, non-steroidal mineralocorticoid receptor antagonists, and statins). The score is the sum of baseline use and changes during follow-up (+1 for initiation of a medication class and -1 for discontinuation). This represents a single composite outcome.

Time frame: Baseline to 12 months

Secondary Outcomes

Number of participants with all-cause mortality

Number of participants who die from any cause during the 12-month follow-up.

Time frame: 12 Months

Outcome Measure: Number of Participants with Worsening Kidney Disease

Number of participants experiencing worsening kidney disease, defined according to the study protocol as ≥40% decline in estimated glomerular filtration rate (eGFR) from enrollment, eGFR \<10 mL/min/1.73 m², initiation of dialysis, or kidney transplantation.

Time frame: 12 Months

Outcome Measure: Number of Participants with Worsening Heart Failure Events

Number of participants experiencing worsening heart failure, including heart failure hospitalization or urgent heart failure visit.

Time frame: 12 Months

Outcome Measure: Major Adverse Cardiovascular Events (MACE)

Number of participants experiencing major adverse cardiovascular events, defined as the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke

Time frame: 12 Months

Outcome Measure: Change from Baseline in Kidney Disease Quality of Life (KDQOL-36) Summary Score

Mean change from baseline to Month 12 in the Kidney Disease Quality of Life (KDQOL-36) summary score. Unit of Measure: Points

Time frame: Baseline and 12 Months

Change in PREVENT-CVD Predicted Cardiovascular Risk Score

Change from baseline to 12 months in predicted cardiovascular risk estimated using the PREVENT-CVD risk calculator among participants without established cardiovascular disease at baseline. Unit of Measure: Percentage points (%)

Time frame: 12 Months

eGFR Total Slope

Annualized rate of change in estimated glomerular filtration rate (eGFR) from baseline through 12 months. Unit of Measure: mL/min/1.73 m²/year

Time frame: 12 Months

Heart-Kidney-Diabetes Multidisciplinary Care MOdels for CardiovascuLar Health In Patients With Chronic Kidney DiSease and Diabetes: A PragmaTIC Cluster Randomized Controlled Trial (HOLISTIC)

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts