Efficacy, Mechanisms and Safety of SGLT2 Inhibitors in Kidney Transplant Recipients

NCT04965935 | Completed Phase 3

• 1 other identifier: 19-5342
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be a randomized, double-blind, placebo-controlled clinical trial comparing the SGLT2 inhibitor dapagliflozin to placebo in 52 kidney transplant recipients (KTR) with or without pre-existing type 2 diabetes (T2D) or post-transplant diabetes mellitus (PTDM). The primary outcome of the trial is to determine if dapagliflozin is superior to placebo in reduction of blood pressure in KTR.

Conditions

Kidney Transplant Recipients; Post-transplant Diabetes Mellitus; Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Systolic blood pressure

  SBP

  Change from baseline systolic blood pressure (SBP) at 12 weeks of treatment

Secondary Outcomes (13)

• Fasting plasma glucose

  Change from baseline fasting plasma glucose at 12 weeks of treatment

• HbA1c

  Change from baseline HbA1c at 12 weeks of treatment

• Continuous home glucose monitoring

  Continuous glucose will be monitored for 14 days at 2 time intervals: 7 days prior to 7 days after drug administration (week -1 to1) and 7 days prior to 7 days after during drug discontinuation (week 11 to 13)

• Arterial stiffness

  Change from baseline arterial stiffness at 12 weeks of treatment

• Systemic vascular resistance

  Change from baseline systemic vascular resistance at 12 weeks of treatment

Study Arms (2)

Dapagliflozin Tablets

EXPERIMENTAL

Patients will be randomized to therapy with dapagliflozin 10mg PO daily for 12 weeks.

Drug: Dapagliflozin 10 MG Oral Tablet

Placebo Matching Dapagliflozin Tablets

PLACEBO COMPARATOR

Patients will be randomized to therapy with placebo matching dapagliflozin tablets PO daily for 12 weeks.

Drug: Placebo Matching Dapagliflozin Oral Tablet

Interventions

Dapagliflozin 10 MG Oral Tablet DRUG

Dapagliflozin will be administered in a dose of 10 mg/day for 12 weeks.

Dapagliflozin Tablets

Placebo Matching Dapagliflozin Oral Tablet DRUG

Placebo will be administered for 12 weeks.

Placebo Matching Dapagliflozin Tablets

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or females \>18 years old ≥ 6months after kidney transplantation;
• In patients with T2D or PTDM, HbA1c \<12.0%;
• eGFR ≥30 ml/min/1.73m\^2 (as per the CKD-EPI equation);
• BMI ≤45kg/m\^2;
• Blood pressure ≤160/90 and ≥90/60 at screening.

You may not qualify if:

• Diagnosis of type 1 diabetes;
• Presence of severe peripheral vascular disease (i.e. prior amputation, gangrene, non-healing ulcer or ischemic rest pain);
• Presence of acute coronary syndrome, stroke or transient ischemic attack in the 3 months prior to screening;
• Prior episode of graft pyelonephritis in the 1 month prior to screening;
• Episode of acute graft rejection in the 3 months prior to screening;
• Initiation of a new immunosuppressive agent or discontinuation of an immunosuppressive agent in the 1 month prior to screening;
• Untreated urinary or genital tract infection;
• Severe hypoglycemia within 3 months of screening, or hypoglycemia unawareness;
• Pre-menopausal women who are nursing, pregnant, or of child-bearing potential and not practicing an acceptable method of birth control;
• Participation in another trial with an investigational drug within 30 days of informed consent;
• Alcohol or drug abuse within 3 months prior to informed consent that would interfere with trial participation;
• Any ongoing clinical condition that would jeopardize subject safety or study compliance based on investigator judgement.
• Patients currently using antipsychotic medications.
• Use of SGLT2 inhibitors within 1 month of starting the study.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Renal Physiology Laboratory

Toronto, Ontario, Canada

Location

Related Publications (1)

• Sridhar VS, Kugathasan L, Lytvyn Y, Liu H, Deng Y, Lovblom LE, Nardone M, Yuen DA, Chen Y, Hua J, Aronson Y, Mohsen M, Kim SJ, Udell JA, Perkins BA, Stevens J, Touw DJ, Heerspink HJL, Cherney DZI, Singh SKS. Efficacy, Mechanisms, and Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Kidney Transplant Recipients: A Randomized, Double-Blind, Placebo-Controlled Trial. Clin J Am Soc Nephrol. 2025 Dec 12. doi: 10.2215/CJN.0000000951. Online ahead of print. No abstract available.

  PMID: 41385300 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Sunita KS Singh, MD MSc FRCPC

  University Health Network, Toronto General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Each bottle of drug will be identified with a unique Composite ID in order to maintain the blind. By way of an Unblinding List, Pharmacy will provide treatment allocations of each Composite ID. The Unblinding List will be maintained within a secure location in the Pharmacy. Blinded personnel will not have access to this list.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinician Scientist

Model Details: Study participants will be allocated to receive either 10 mg daily of dapagliflozin or a matching placebo for 12 weeks in a 1:1 ratio while continuing on existing medical therapy for glycemic control as recommended by Diabetes Canada.

Study Record Dates

• First Submitted: May 21, 2021
• First Posted: July 16, 2021
• Study Start: July 15, 2021
• Primary Completion: August 30, 2024
• Study Completion: August 30, 2024
• Last Updated: March 20, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)