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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Kidney Disease; Type II Diabetes
• Intervention / Treatment: Other: The intervention with the MCM is Kidney-Heart GDMT initiation and titration for dose optimization (as clinically tolerated), within 4 months of enrollment in the study.

Detailed Description

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
• Enrollment (Estimated): 570
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: C. Michael Gibson, MS, MD Chief Executive Officer, MS, MD; Phone Number: 617-307-5200; Email: info@baiminstitute.org
• Study Contact Backup: Name: Patricia Wedge M Chief Operating Officer, RN, BSN, CCRC; Phone Number: 617-307-5320; Email: patricia.wedge@baiminstitute.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: multidisciplinary care model (MCM) intervention; This model/arm will include Primary Care Clinician (PCC) delivered care assisted by a Multidisciplinary Heart-Kidney-Diabetes Care Team Model (MCM)	Other: The intervention with the MCM is Kidney-Heart GDMT initiation and titration for dose optimization (as clinically tolerated), within 4 months of enrollment in the study.; The intervention with the MCM is Kidney-Heart GDMT initiation and titration for dose optimization (as clinically tolerated), within 4 months of enrollment in the study.
No Intervention: a usual care model (UCM); This model/arm will include PCC delivered care with as-needed Local Specialist Support, representing the Usual Care Model (UCM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with all-cause mortality	Number of participants who die from any cause during the 12-month follow-up.	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.	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.	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	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	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 (%)	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	12 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Outcome Measure 1: Number of participants with acute kidney injury	Acute kidney injury defined according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria as an increase in serum creatinine of ≥0.3 mg/dL within 48 hours or an increase in serum creatinine to ≥1.5 times baseline within 7 days. Unit of Measure: Participants with event	12 Months
Safety Outcome Measure 2: Number of participants with hypotension	Hypotension defined as systolic blood pressure <90 mmHg or symptomatic hypotension requiring clinical intervention, medication adjustment, or study drug discontinuation. Unit of Measure: Participants with event	12 Months
Safety Outcome Measure: Number of participants with volume depletion	Volume depletion defined as clinical evidence of dehydration or hypovolemia requiring fluid replacement, medication adjustment, emergency department evaluation, or hospitalization. Unit of Measure: Participants with event	12 Months
Safety Outcome Measure Title: Number of participants with hyperkalemia	Hyperkalemia defined as clinically significant elevation in serum potassium requiring clinical intervention, medication adjustment, emergency department evaluation, or hospitalization, according to the study protocol. Unit of Measure: Participants with event	12 Months
Safety Outcome Measure: Number of participants with hypoglycemia	Hypoglycemia defined according to American Diabetes Association (ADA) Standards of Care as blood glucose <70 mg/dL (Level 1 hypoglycemia). Severe hypoglycemia is defined as an event requiring assistance from another person. Unit of Measure: Participants with event	12 Months

Collaborators and Investigators

• Sponsor: Baim Institute for Clinical Research

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: June 5, 2026
• First Submitted That Met QC Criteria: September 3, 2026
• First Posted (Actual): September 10, 2026

Study Record Updates

• Last Update Posted (Actual): September 10, 2026
• Last Update Submitted That Met QC Criteria: September 3, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Cardiovascular-kidney-metabolic; Multidisciplinary Care Model; Guideline Directed Medical Therapies
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Renal Insufficiency, Chronic
• Other Study ID Numbers: BICR 2026-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No