Effect of Subcutaneous Semaglutide on Kidney Transplant Candidacy

A RAndomized trIal Examining the Effect of Subcutaneous Semaglutide on Kidney Transplant Candidacy for Patients With Stage 4-5 CKD or Dialysis-dependent ESKD

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04741074

Acronym

RAISE-KT

Enrollment

Registered

2021-02-05

Start date

2021-07-23

Completion date

2023-01-31

Last updated

2024-02-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

CKD, Diabetic Kidney Disease, Obesity, Severe Obesity, Type 2 Diabetes Mellitus in Obese

Keywords

ckd, obesity, kidney transplant, transplant wait list, diabetic kidney disease, glp-1, semaglutide

Brief summary

This randomized study evaluates the effect of subcutaneous semaglutide /in combination with lifestyle counseling in patients with type 2 diabetes mellitus (T2DM), overweight/obesity, and stage 4-5 chronic kidney disease (CKD) or dialysis-dependent end-stage kidney disease (ESKD) on patients' eligibility for kidney transplantation at the end of 9 months.

Detailed description

Transplant policies regarding listing consider uncontrolled diabetes and severe obesity to be contraindications though there is great variability for exact BMI (35-45 kg/m2) and A1c (9-10%) thresholds for listing by center. Glucagon-lowering peptide-1 receptor agonists (GLP-1 RAs) offer great promise in this population as they have been shown to reduce weight, central adiposity, A1c, and risk of cardiovascular outcomes with similar effects in patients with and without CKD. In this double-blind, placebo-controlled randomized controlled trial, the investigators will evaluate the effect of subcutaneous semaglutide 1.34 mg/ml (up to 1.0 mg per week) in combination with lifestyle counseling in patients with T2DM, overweight/obesity, and stage 4-5 CKD or dialysis-dependent ESKD on patients' eligibility for kidney transplantation in terms of diabetes control (A1c \<9%) and obesity (BMI \<35 kg/m2 or 35-40 kg/m2 with waist circumference \<120 cm) at the end of 9 months.

Interventions

DRUGSemaglutide 2 mg/1.5 ml (1.34 mg/ml), prefilled pen-injector for subcutaneous injection solution

Dose will be started at 0.25 mg per week. Dose escalation will occur every 4 weeks to mitigate risk of gastrointestinal side effects to a maximum dose of 1.0 mg per week.

DRUGPlacebo 1.5 ml, prefilled pen-injector for subcutaneous injection solution

Matched placebo solution for injection will be provided by Novo Nordisk in a 1.5 ml pre-filled pen-injector for subcutaneous injection with the same instructions on dose escalation.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

This is a placebo-controlled double-blind clinical trial. Study investigators and participants will be blinded to treatment allocation.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. \- Age ≥ 18 years 2. \- BMI 25-45 kg/m2 3. \- T2DM 4. \- Advanced CKD\* (last eGFR \<30 ml/min/1.73m2 in EHR or ESKD on dialysis prior to screening) or stage G3B/A2-3 CKD (eGFR 30 to \<45 ml/min/1.73m2 with albumin/creatinine ratio \>30 mg/g). 5. \- Fulfill kidney transplant listing criteria except for one or more of the following reasons (1: uncontrolled diabetes \[A1c ≥9%); 2: severe obesity (BMI ≥ 40 kg/m2 or BMI 35-40 kg/m2 with waist circumference \>120 cm). See

Exclusion criteria

for general contraindications used for transplant listing used by majority of U.S. transplant centers\]. 6. \- Ability to provide informed consent before any trial-related activities 7. \- Access to a telephone * The cause of the CKD does not need to be due specifically to diabetes

Design outcomes

Primary

Measure	Time frame	Description
Kidney Transplant Eligibility	Ascertained at the end of 9 months	Proportion either listed for kidney transplant at 9 months or meeting the following kidney transplant candidacy criteria for A1c (\<9%) and obesity (BMI \<35 kg/m2 or BMI 35-40 kg/m2 with waist circumference \<120 cm)

Secondary

Measure	Time frame	Description
Change in BMI	From baseline to 9 months	Weight will be measured at each study visit in light clothing without shoes by trained, certified staff using a calibrated, digital scale. Scales will be calibrated annually. Height will be measured at the initial study visit to the nearest 0.1 cm using a calibrated, wall-mounted stadiometer without shoes on a firm, level surface, with head in the horizontal plane.
Change in Waist Circumference	From baseline to 9 months	Waist circumference will be measured at each study visit to the nearest 0.1 cm using a Gulick II tape measure.
Change in Waist-to-hip Ratio	From baseline to 9 months	Hip circumference will also be measured to the nearest 0.1 cm using a Gulick II tape measure, and waist-to-hip ratio will be calculated.
Change in Hemoglobin A1c (HgbA1c)	From baseline to 9 months	HgbA1c will be collected using routine procedures and measured on the same day at the central Geisinger laboratory by Turbidimetric inhibition immunoassay.
New Activation on the Transplant List	Assessed at end of 9 months	Proportion of participants who were newly added to a transplant list during study period. Assessed by Geisinger kidney transplant committee (blinded to randomization assignment, independent of investigators)
Receipt of Kidney Transplant	Assessed at end of 9 months	Confirmed by review of electronic health record (EHR)
Change in Body Fat Percentage	From baseline to 9 months	Measured using bioelectrical impedance analysis

Other

Measure	Time frame	Description
Change in Estimated Glomerular Filtration (eGFR) Rate Among Subset of Participants Without End-stage Kidney Disease	Baseline to 9 months	Testing at central Geisinger lab; Creatinine-based CKD-EPI equation
All-cause Hospitalizations	Entire 9-month study period	Collected using Geisinger EHR data
Cardiovascular Disease (CVD) Events	Entire 9-month study period	Collected using Geisinger EHR data using ICD codes for CVD-related hospitalizations
Proportion Experiencing Doubling of Creatinine or End-stage Kidney Disease	Entire 9-month study period	Collected using Geisinger EHR data using ICD codes
Proportion Experiencing Death	Entire 9-month study period	Collected using Geisinger EHR data
Proportion Experiencing Injection-site Reactions	Entire 9-month study period	Assessed at each study visit
Proportion Experiencing Gallbladder Disorders	Entire 9-month study period	Assessed at each study visit
Proportion Experiencing Neoplasms	Entire 9-month study period	Assessed at each study visit
Proportion Experiencing Hepatic Events	Entire 9-month study period	Assessed at each study visit
Proportion Experiencing Allergic Reactions	Entire 9-month study period	Assessed at each study visit
Proportion Experiencing Gastrointestinal Disorders	Entire 9-month study period	Assessed at each study visit
Proportion Experiencing Hypoglycemia Events	Entire 9-month study period	Assessed at each study visit
Proportion Experiencing Acute Pancreatitis Events	Entire 9-month study period	Assessed at each study visit
Change in Low-Density Lipoprotein (LDL)	Baseline to 9 months	Collected at a Geisinger lab using routine procedures and measured on the same day at the central Geisinger laboratory by spectrophotometry.
Change in Triglycerides	Baseline to 9 months	Collected at a Geisinger lab using routine procedures and measured on the same day at the central Geisinger laboratory by spectrophotometry.
Change in Systolic Blood Pressure	Baseline to 9 months	Automated office blood pressure (AOBP) will be measured (attended) using the OMRON 907-XL machine, with a 5-minute rest period in the seated position, followed by 3 measurements separated by 1-minute time intervals by trained research staff. Mid-arm circumference will be measured, and a cuff of appropriate size will be identified and the same size cuff will used for both visits.
Change in Diastolic Blood Pressure	Baseline to 9 months	Automated office blood pressure (AOBP) will be measured (attended) using the OMRON 907-XL machine, with a 5-minute rest period in the seated position, followed by 3 measurements separated by 1-minute time intervals by trained research staff. Mid-arm circumference will be measured, and a cuff of appropriate size will be identified and the same size cuff will used for both visits.
Change in Albuminuria Among Subset of Participants Without End-stage Kidney Disease	Baseline to 9 months	Testing at the central Geisinger laboratory, using immunoturbidimetry (albumin) and Jaffe/Enzymatic (Urine Creatinine)

Countries

United States

Participant flow

Participants by arm

Arm	Count
Semaglutide This arm will receive semaglutide. Semaglutide 2 mg/1.5 ml (1.34 mg/ml), prefilled pen-injector for subcutaneous injection solution: Dose will be started at 0.25 mg per week. Dose escalation will occur every 4 weeks to mitigate risk of gastrointestinal side effects to a maximum dose of 1.0 mg per week.	7
Placebo This arm will receive placebo. Placebo 1.5 ml, prefilled pen-injector for subcutaneous injection solution: Matched placebo solution for injection will be provided by Novo Nordisk in a 1.5 ml pre-filled pen-injector for subcutaneous injection with the same instructions on dose escalation.	8
Total	15

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Study terminated prematurely	1	0
Overall Study	Withdrawal by Subject	1	1

Baseline characteristics

Characteristic	Placebo	Total	Semaglutide
Age, Continuous Age	59.13 years STANDARD_DEVIATION 14.88	60.60 years STANDARD_DEVIATION 11.84	62.29 years STANDARD_DEVIATION 3
BMI	40.20 kg/m^2 STANDARD_DEVIATION 4.12	39.95 kg/m^2 STANDARD_DEVIATION 4.57	39.7 kg/m^2 STANDARD_DEVIATION 5.37
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants	15 Participants	7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Hemoglobin A1c	6.70 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.5	6.75 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.31	6.8 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.38
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	2 Participants	2 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	6 Participants	13 Participants	7 Participants
Region of Enrollment United States	8 participants	15 participants	7 participants
Sex: Female, Male Female	5 Participants	8 Participants	3 Participants
Sex: Female, Male Male	3 Participants	7 Participants	4 Participants
Waist circumference	124.20 cm STANDARD_DEVIATION 9.77	128.01 cm STANDARD_DEVIATION 13.16	132.37 cm STANDARD_DEVIATION 5.99

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 7	0 / 8
other Total, other adverse events	5 / 7	8 / 8
serious Total, serious adverse events	2 / 7	3 / 8

Outcome results

Primary

Kidney Transplant Eligibility

Proportion either listed for kidney transplant at 9 months or meeting the following kidney transplant candidacy criteria for A1c (\<9%) and obesity (BMI \<35 kg/m2 or BMI 35-40 kg/m2 with waist circumference \<120 cm)

Time frame: Ascertained at the end of 9 months

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Semaglutide	Kidney Transplant Eligibility	3 Participants
Placebo	Kidney Transplant Eligibility	2 Participants

Secondary

Change in BMI

Weight will be measured at each study visit in light clothing without shoes by trained, certified staff using a calibrated, digital scale. Scales will be calibrated annually. Height will be measured at the initial study visit to the nearest 0.1 cm using a calibrated, wall-mounted stadiometer without shoes on a firm, level surface, with head in the horizontal plane.