Chronic Kidney Disease, Type 2 Diabetes
Conditions
Keywords
Chronic Kidney Disease, Type 2 Diabetes, Rapid Therapy Initiation, Guideline-Directed Medical Therapy, Renin-Angiotensin System Inhibitors, Sodium-Glucose Cotransporter 2 Inhibitors, Non-steroidal Mineralocorticoid Receptor Antagonist, Glucagon-Like Peptide-1 Receptor Agonist, Albuminuria, Estimated Glomerular Filtration Rate, Hyperkalemia
Brief summary
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
Detailed description
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.
Interventions
DRUGLisinopril
5-20mg daily
DRUGUnivasc
3.75-15mg daily
DRUGAceon
4-16mg daily
DRUGAccupril
10-40mg daily
DRUGAltace
1.25-5mg daily
DRUGMavik
1-4mg daily
DRUGEdarbi
40-80mg daily
DRUGAtacand
8-32mg daily
DRUGAvapro
150-300mg daily
DRUGCozaar
25-100mg daily
DRUGBenicar
20-40mg daily
DRUGMicardis
20-80mg daily
DRUGDiovan
80-320mg daily
DRUGInvokana
100mg daily
DRUGFarxiga
10mg daily
DRUGJardiance
10mg daily
DRUGErtugliflozin
5mg daily
DRUGBrenzavvy
20mg daily
DRUGSotagliflozin
200-400mg daily
DRUGFinerenone
10-40mg daily
DRUGSemaglutide
.25-1.0mg 1 time a week
DRUGLotensin
10-40mg daily
DRUGCapoten
12.5-50mg 3 times a day
DRUGEnalapril
2.5-10mg daily
DRUGMonopril
10-40mg daily
Sponsors
Baylor Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants are randomized in a 1:1 ratio to either a rapid, simultaneous therapy initiation approach or usual care with slow, sequential initiation of therapies.
Eligibility
Sex/Gender
ALL
Age
18 Years to 84 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| On-study retention rate at 6 months | 6 months | Proportion of participants who remain on all four guideline-directed CKD therapies at maximally tolerated doses without permanent discontinuation |
| Sustained decline in eGFR ≥30% | 6 months | Proportion of participants with sustained decline in estimated glomerular filtration rate (eGFR; two consecutive readings ≥2 weeks apart) |
| Change in UACR | 6 months | Relative change in log-transformed urine albumin-to-creatinine ratio (UACR) from baseline to 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Enrollment rate | 6 months | Number of participants enrolled per month |
| Protocol adherence | 6 months | Proportion of participants initiating all four therapies within 8 weeks |
| Treatment discontinuation | 6 months | Proportion of participants who permanently discontinue one or more therapies |
| Moderate Hyperkalemia | 6 months | Incidence of potassium levels greater than 5.5 to less than or equal to 6.0 mmol/L |
| Severe Hyperkalemia | 6 months | Incidence of potassium levels greater than 6.0 mmol/L |
| Acute Kidney Injury | 6 months | 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 |
| End-stage kidney disease | 6 months | 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) |
| Number of participants with permanent drug discontinuation | 6 months | Number of participants with permanent discontinuation of one or more study drugs not due to study completion or death. |
| Rate of change in estimated glomerular filtration rate (slope) | 6 months | Rate of change in estimated glomerular filtration rate over the 6-month study period |
| Change in glycated hemoglobin (HbA1c) | 6 months | Change in glycated hemoglobin (HbA1c) levels from baseline |
| Number of participants who achieve >30% reduction in urine albumin-to-creatinine ratio | 6 months | Number of participants achieving \>30% reduction in urine albumin-to-creatinine ratio |
| Change in Kidney Disease Quality of Life-36 score | 6 months | 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. |
| Change in Patient-Reported Outcomes Measurement Information System score | 6 months | 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. |
| Change in Treatment Burden Questionnaire (TBQ) score | 6 months | 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. |
| Change in Living with Medicines Questionnaire version 3 score | 6 months | 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. |
Countries
United States
Contacts
CONTACTShahzeb Khan, MD
Outcome results
None listed