Rapid and Simultaneous Initiation of Four Guideline-Directed CKD Therapies (RAPID-CKD)

Phase 4Not Yet RecruitingNCT07547878

Baylor Research Institute64 enrolled

Overview

The goal of this clinical trial is to learn if starting four kidney disease medicines quickly and together (a rapid treatment approach) is safe and works well in people with type 2 diabetes and chronic kidney disease. The main questions it aims to answer are: * Is it safe to start these medicines over a short period of time? * How often do kidney function changes or high potassium levels occur? * Does this approach lower protein in the urine (a sign of kidney damage)? * How many participants are able to stay on all four medicines over 6 months? Researchers will compare this approach to usual care, where medicines are started one at a time over several months. Participants will: Be assigned by chance to either this approach or usual care Start up to four approved kidney medicines over about 8 weeks (rapid treatment approach) or follow standard care Have regular clinic visits and lab tests to check kidney function and potassium levels Be followed for about 6 months

This study is a pilot, open-label, randomized clinical trial designed to evaluate the feasibility, safety, and effectiveness of rapidly starting multiple guideline-recommended therapies in people with type 2 diabetes and chronic kidney disease. In current clinical practice, these medicines are usually started one at a time over many months. This step-by-step approach may delay potential benefits and leave people at continued risk of kidney disease progression and cardiovascular complications. This study will test a different approach, where these therapies are started in a structured and closely monitored way over a short period of time. Participants will be randomly assigned to either a rapid initiation strategy or usual care. In the rapid group, up to four approved therapies will be started and adjusted over approximately 8 weeks using a structured treatment plan. In the usual care group, treatment will follow standard clinical practice, where medications are introduced gradually at the discretion of the treating clinician. Participants in both groups will be followed for 6 months. During this time, they will have regular clinic visits and laboratory testing to monitor kidney function, potassium levels, and overall treatment tolerance. This pilot study will provide important information on whether this rapid treatment approach can be safely implemented in real-world clinical settings and whether participants are able to start and continue multiple therapies within a short time frame.

Study Type

INTERVENTIONAL

Allocation

Interventions

FinerenoneDRUG

10-40mg daily

SemaglutideDRUG

.25-1.0mg 1 time a week

LotensinDRUG

10-40mg daily

CapotenDRUG

12.5-50mg 3 times a day

EnalaprilDRUG

2.5-10mg daily

MonoprilDRUG

10-40mg daily

LisinoprilDRUG

5-20mg daily

UnivascDRUG

3.75-15mg daily

AceonDRUG

4-16mg daily

AccuprilDRUG

10-40mg daily

AltaceDRUG

1.25-5mg daily

MavikDRUG

1-4mg daily

EdarbiDRUG

40-80mg daily

AtacandDRUG

8-32mg daily

AvaproDRUG

150-300mg daily

CozaarDRUG

25-100mg daily

BenicarDRUG

20-40mg daily

MicardisDRUG

20-80mg daily

DiovanDRUG

80-320mg daily

InvokanaDRUG

100mg daily

FarxigaDRUG

10mg daily

JardianceDRUG

10mg daily

ErtugliflozinDRUG

5mg daily

BrenzavvyDRUG

20mg daily

SotagliflozinDRUG

200-400mg daily

Eligibility

Sex: ALLMin age: 18 YearsMax age: 84 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients aged 18-84 years * eGFR 45 to ≤90 mL/min/1.73 m2 * UACR \>200 mg/g * diagnosis of T2D * receiving ≤2 guideline-recommended drug classes irrespective of dose for ≥4 weeks prior to screening * eligible for all 4 drugs * systolic BP (SBP) \>90 mmHg * those willing to provide written informed consent and to adhere to study visits. Exclusion Criteria: * Type 1 diabetes * any known primary non-diabetic kidney disease (i.e., polycystic kidney disease, glomerulonephritis, interstitial nephritis, etc.) * history of kidney transplant * liver disease (i.e., aspartate transaminase or alanine transaminase \>5 times, or bilirubin \>3 times the upper limit of normal) * serum potassium \>5.5 mEq/L at baseline * known hypersensitivity to any study drug * life expectancy \<6 months * active malignancy or infection * brittle diabetes (defined as severe glycemic instability with hospitalization or emergency care for hypoglycemia or hyperglycemia within the past 6 months) * high-risk of hypoglycemia (Clarke or Gold score ≥4) * predicted 12-month risk of hypoglycemia related emergency visits or hospitalizations \>5% using the Kaiser Permanente hypoglycemia prediction score * high dose insulin use (\>1 unit/kg/day). * RASi: hyperkalemia or angioedema * SGLT2i: diabetic ketoacidosis, type 1 diabetes, recurrent genitourinary infections * ns-MRA: hyperkalemia * GLP1-RA: personal or family history of medullary thyroid carcinoma, known gastroparesis, or pancreatitis.

Outcomes

Primary Outcomes

On-study retention rate at 6 months

Proportion of participants who remain on all four guideline-directed CKD therapies at maximally tolerated doses without permanent discontinuation

Time frame: 6 months

Sustained decline in eGFR ≥30%

Proportion of participants with sustained decline in estimated glomerular filtration rate (eGFR; two consecutive readings ≥2 weeks apart)

Time frame: 6 months

Change in UACR

Relative change in log-transformed urine albumin-to-creatinine ratio (UACR) from baseline to 6 months

Time frame: 6 months

Secondary Outcomes

Enrollment rate

Number of participants enrolled per month

Time frame: 6 months

Protocol adherence

Proportion of participants initiating all four therapies within 8 weeks

Time frame: 6 months

Treatment discontinuation

Proportion of participants who permanently discontinue one or more therapies

Time frame: 6 months

Moderate Hyperkalemia

Incidence of potassium levels greater than 5.5 to less than or equal to 6.0 mmol/L

Time frame: 6 months

Severe Hyperkalemia

Incidence of potassium levels greater than 6.0 mmol/L

Time frame: 6 months

Acute Kidney Injury

Incidence of acute kidney injury (AKI) events (persistent estimated glomerular filtration rate decline ≥30% without return to \<30% with drug discontinuation; or hospitalization with diagnosis of AKI related to medications) during the study period

Time frame: 6 months

End-stage kidney disease

Incidence of progression to end-stage kidney disease (initiation of chronic dialysis \[hemo- or peritoneal dialysis\] for ≥90 days or kidney transplantation, or persistent \[≥2 values, including the last value if not on dialysis or transplant\] estimated glomerular filtration rate \<15 mL/min/1.73m\^2)

Time frame: 6 months

Number of participants with permanent drug discontinuation

Number of participants with permanent discontinuation of one or more study drugs not due to study completion or death.

Time frame: 6 months

Rate of change in estimated glomerular filtration rate (slope)

Rate of change in estimated glomerular filtration rate over the 6-month study period

Time frame: 6 months

Change in glycated hemoglobin (HbA1c)

Change in glycated hemoglobin (HbA1c) levels from baseline

Time frame: 6 months

Number of participants who achieve >30% reduction in urine albumin-to-creatinine ratio

Number of participants achieving \>30% reduction in urine albumin-to-creatinine ratio

Time frame: 6 months

Change in Kidney Disease Quality of Life-36 score

Change from baseline in Kidney Disease Quality of Life-36 (KDQOL-36) score. Scores range from 0 to 100, with higher scores indicating better quality of life.

Time frame: 6 months

Change in Patient-Reported Outcomes Measurement Information System score

Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) score. PROMIS includes seven domains: Physical Function, Anxiety, Depression, Fatigue, Sleep Disturbance, Ability to Participate in Social Roles and Activities, and Pain Interference. Each domain includes 4 items scored from 1 to 5, with raw domain scores ranging from 4 to 20, and domain scores are converted to standardized T-scores with a mean of 50 and standard deviation of 10. A separate Pain Intensity item is rated on a 0 to 10 scale, where 0 indicates no pain and 10 indicates worst imaginable pain. For Physical Function and Ability to Participate in Social Roles and Activities, higher scores indicate better health. For Anxiety, Depression, Fatigue, Sleep Disturbance, Pain Interference, and Pain Intensity, higher scores indicate greater symptom burden or worse health status.

Time frame: 6 months

Change in Treatment Burden Questionnaire (TBQ) score

Change from baseline in Treatment Burden Questionnaire (TBQ) score. TBQ is composed of 13 items rated on a Likert scale ranging from 0 (not a problem) to 10 (big problem) and assesses the burden associated with taking medicine, self-monitoring, laboratory tests, doctor visits, need for organization, administrative tasks, following advice on diet and physical activity, and social impact of the treatment. TBQ item scores can be summed into a global score, ranging from 0 to 130. Higher scores indicating greater treatment burden.

Time frame: 6 months

Change in Living with Medicines Questionnaire version 3 score

Change from baseline in Living with Medicines Questionnaire version 3 (LMQ-3) score. LMQ-3 consists of 41 items scored on a 5-point Likert scale. Total scores range from 41 to 205, with higher scores indicating greater treatment burden.

Time frame: 6 months

Rapid and Simultaneous Initiation of Four Guideline-Directed CKD Therapies (RAPID-CKD)

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts