Empagliflozin on Residual Kidney Function in Incident Peritoneal Dialysis Patients

NCT ID: NCT06483074

Last Updated: 2025-08-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-29
• Study Completion Date: 2026-10-31

Brief Summary

Empagliflozin, a new class of diabetes medication, has demonstrated a reduction in renal function decline among patients with chronic kidney disease, regardless of their diabetes status. However, all previous studies excluded dialysis patients. Patients starting dialysis may still produce a certain amount of urine. Importantly, patients with better preserved residual kidney function tend to have better control of blood pressure and volume status, improved nutrition status, higher quality of life and reduced mortality rate.

The purpose of this study is to learn about the safety of empagliflozin in patients on peritoneal dialysis, in preparation for a future large clinical trial. Participants who newly initiate peritoneal dialysis will be randomly allocated to either empagliflozin on top of standard of care, or standard of care alone. Over a follow-up period of six months, the investigators will collect information on urine volume, blood pressure and glucose control. Safety, tolerability and drug compliance of empagliflozin will also be evaluated. If empagliflozin is found to be safe and well tolerated in patients on peritoneal dialysis, further large-scale randomized controlled trial may be conducted to evaluate its impact on residual kidney function and other relevant clinical outcomes.

Detailed Description

Diabetes is the leading cause of end stage kidney disease in developed countries. Peritoneal dialysis (PD) is a home-based and cost-effective modality of kidney placement therapy. Maintenance of residual kidney function (RKF) is one of the most crucial objectives to improve outcomes of PD patients. Observational studies showed that residual urine volume or residual glomerular filtration rate (GFR), but not peritoneal creatinine clearance, independently predicted patient survival. This benefit is likely attributed to better volume control, improved nutritional status, preserved endocrine function and enhanced clearance of uremic toxins in the presence of RKF. However, current therapeutic strategies to preserve RKF were most limited to the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and biocompatible PD solutions.

Hong Kong adopted the 'PD-first' policy since 1985, and has the highest proportion of PD patients in the world. Inadequate dialysis, which is directly related to the loss of RKF, is the second most common reason for a permanent transfer to hemodialysis among PD patients. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been shown to reduce albuminuria and delay progression of chronic kidney disease even in patients with advanced stages of kidney disease. It is postulated that the renoprotective effect of SGLT-2 inhibitors may be extended to dialysis population since a considerable proportion of patients still have urine output. SGLT2 inhibitors may potentially attenuate GFR decline in PD patients because heavy proteinuria independently predicted decline in residual GFR and onset of anuria. Moreover, preclinical studies suggested that empagliflozin reduced inflammation and oxidative stress by decreasing proinflammatory cytokines, inducing expression of anti-inflammatory M2 phenotype of macrophages, and antagonizing the effect of advanced glycation products. This beneficial effect may be particularly relevant to PD patients, where subclinical inflammation is common and inversely correlated with RKF.

Despite the potential promising effect of SGLT2-inhibitors in RKF in PD patients, dialysis patients were excluded in previous randomized controlled trials. In the present study, the investigators hypothesize that oral empagliflozin in addition to RAAS inhibitor, compared to RAAS inhibitor alone, better preserves RKF in patients newly started on PD. After a run-in period of 6 to 8 weeks where the dose of RAAS inhibitors are uptitrated to maximally tolerated dose, 48 incident PD patients will be randomized to empagliflozin or control (no empagliflozin) for a total of 6 months. This study aims to explore the feasibility of conducting a full-scale, adequately powered randomized controlled trial that investigates the effect of empagliflozin on RKF in incident PD patients.

Conditions

End Stage Renal Disease on Dialysis; Peritoneal Dialysis Complication; Sodium-glucose Cotransporter-2 Inhibitor; Residual Kidney Function

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Intervention group

Patients randomized to intervention group will receive oral empagliflozin 10mg daily on top of optimized dose of RAAS inhibitor for 6 months

Group Type: ACTIVE_COMPARATOR

Empagliflozin 10 MG

Intervention Type: DRUG

empagliflozin oral 10mg daily for 6 months

Control group

Patients randomized to control group will receive optimized dose of RAAS inhibitor for 6 months

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Empagliflozin 10 MG

empagliflozin oral 10mg daily for 6 months

Intervention Type: DRUG

Other Intervention Names

Jardiance 10mg daily

Eligibility Criteria

Inclusion Criteria

1. Incident PD patients within 90 days of Tenckhoff catheter insertion

2. Age 18-75 years old

3. Patient with or without history of Type 2 diabetes

4. Residual GFR (defined as the average of 24-hour urinary urea and creatinine clearances) > 2ml/min/1.73m2 AND urine volume > 400ml per day

5. Patients who are willing to provide written informed consent

Exclusion Criteria

1. Patients with history of hemodialysis (≥ 3 months) or renal transplant

2. Life expectancy <6 months

3. Prior use of any type of SGLT2 inhibitors within 1 month before screening visit

4. Poorly controlled diabetes with HBA1c >11%

5. Type 1 diabetes

6. History of any active malignancy within 5 years (except curatively resected basal cell or squamous cell skin cancers)

7. Peritonitis within 4 weeks

8. Ketoacidosis within 5 years

9. Known hypersensitivity to empagliflozin or other SGLT2 inhibitors

10. Any active acute or chronic physical or mental conditions that, in the opinion of the investigator, might interfere with the compliance of participants to or the performance of this study

11. Participation in any clinical trial or use of any investigational medicinal product 1 month before screening visit

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Cheuk-Chun SZETO

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jack KC Ng, FRCP

Role: PRINCIPAL_INVESTIGATOR

Chinese University of Hong Kong

Cheuk Chun Szeto, MD, FRCP

Role: STUDY_DIRECTOR

Chinese University of Hong Kong

Locations

Chinese University of Hong Kong

Hong Kong, , Hong Kong

Site Status: RECRUITING

Countries

Hong Kong

Central Contacts

Jack KC Ng, FRCP

Role: CONTACT

jackng@cuhk.edu.hk

+852 37636098

Phyllis Cheng, BN

Role: CONTACT

pcheng809@yahoo.com.hk

+852 35053528

Facility Contacts

Jack KC Ng, FRCP

Role: primary

jackng@cuhk.edu.hk

85237636098

Other Identifiers

CREC 2024.090-T

Identifier Type: -

Identifier Source: org_study_id