DAPAGLIFLOZIN for Kidney transplantation

Inclusion criteria

• {"criterion_text":"- Renal transplant recipients transplanted 6 (±2) weeks earlier at OUH Rikshospitalet.\n- Age 18-75 years.\n- Able to comply with the medical treatment on their own.\n- Calcineurin inhibitor trough concentrations in accordance with individual therapeutic range and standard dose prednisolone and mycophenolate mofetil over the last 2 weeks.\n- Estimated GFR (EKFC-formula) ≥25 mL/min/1.73 m2."}

Exclusion criteria

• {"criterion_text":"- Type 1 diabetes.\n- Rejection episodes of the kidney graft prior to randomization.\n- Ongoing infectious disease or intermittent causes affecting renal function, e.g. untreated obstructive lymphocele.\n- Malnutrition.\n- Urosepsis less than 1 year prior to randomization.\n- Participants with a known hypersensitivity to dapagliflozin or any of the excipients of the product.\n- Women who are breastfeeding, pregnant patients or women of childbearing potential (WOCBP) not on highly effective contraception (not acceptable methods: progesterone-only oral hormonal contraception, male/female condom without spermicide or cap, diaphragm or sponge with spermicide. See also section 6.8)."}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is the difference in eGFR slope between groups from before randomization to 3 years after transplantation. The slope is to be determined by mixed model statistics including MDRD4 formula estimated GFR from at least four creatinine measurements per year.","definition_or_measurement_approach":"eGFR slope determined by mixed model statistics including MDRD4 formula estimated GFR from at least four creatinine measurements per year."}

Secondary endpoints

• {"endpoint_text":"- Difference between groups in the slope of urinary protein/creatinine ratio over the first 72 and 150 weeks of treatment, respectively, assessed from at least four urine samples per year using mixed model statistics.","definition_or_measurement_approach":"Slope of urinary protein/creatinine ratio over first 72 and 150 weeks; assessed from at least four urine samples per year using mixed model statistics."}
• {"endpoint_text":"- Difference between groups in blood pressure from before to 72 and 150 weeks of treatment","definition_or_measurement_approach":"Change in blood pressure measured from baseline to 72 and 150 weeks."}
• {"endpoint_text":"- Difference between groups in changes of measured GFR (iohexol serum clearance) from 2 weeks to 72 weeks and 150 weeks of treatment","definition_or_measurement_approach":"Measured GFR by iohexol serum clearance comparing change from 2 weeks to 72 and 150 weeks."}
• {"endpoint_text":"- Difference between groups in changes of DXA-measured percent subcutaneous and visceral fat in relation to total fat mass from 2 weeks to 72 weeks of treatment","definition_or_measurement_approach":"DXA-measured percent subcutaneous and visceral fat relative to total fat mass, change from 2 to 72 weeks."}
• {"endpoint_text":"- Difference between groups in glucose tolerance assess by an oral glucose tolerance test before to 72 weeks of treatment","definition_or_measurement_approach":"Oral glucose tolerance test comparing baseline to 72 weeks."}
• {"endpoint_text":"- Difference between groups in urinary metabolomic profile from before to 72 weeks of treatment (explorative endpoint)","definition_or_measurement_approach":"Urinary metabolomic profiling comparing baseline to 72 weeks (explorative)."}
• {"endpoint_text":"- Difference between groups in number of patients with at least one biopsy proven acute rejection episode up to 150 weeks of treatment","definition_or_measurement_approach":"Incidence count of biopsy-proven acute rejection episodes up to 150 weeks."}
• {"endpoint_text":"- Difference between groups in adverse events such as genital candida infections, lower urinary tract infections, ketoacidosis and Fourniers gangrene over the first 72 and 150 weeks of treatment, respectively","definition_or_measurement_approach":"Incidence of listed adverse events over first 72 and 150 weeks."}
• {"endpoint_text":"- Difference between groups in selected clinical chemistry markers (hemoglobin, hematocrit, sodium, potassium, magnesium and uric acid) before, at 72 and at 150 weeks of treatment","definition_or_measurement_approach":"Changes in specified clinical chemistry markers at baseline, 72 and 150 weeks."}
• {"endpoint_text":"- Difference between groups in degree of change in inflammation-score (Immunohistochemistry analysis with regards to amount of collagen and extracellular markers.) in protocol biopsies from before to 72 weeks of treatment","definition_or_measurement_approach":"Immunohistochemistry-derived inflammation score (collagen and extracellular markers) change from baseline to 72 weeks in protocol biopsies."}
• {"endpoint_text":"- Difference between groups in degree of change in fibrosis-score (Semi-quantitative estimation of percent graft fibrosis in the renal cortex) in protocol biopsies from before to 72 weeks of treatment","definition_or_measurement_approach":"Semi-quantitative percent graft fibrosis in renal cortex in protocol biopsies comparing baseline to 72 weeks."}
• {"endpoint_text":"- Difference between groups in changes in kidney graft mRNA and protein expression patterns from before to 72 weeks of treatment (explorative endpoint)","definition_or_measurement_approach":"mRNA and protein expression pattern changes in kidney graft tissue from baseline to 72 weeks (explorative)."}
• {"endpoint_text":"- Difference between groups in the 10-year extended eGFR slope from annual plasma creatinine values reported to NRR after year 3","definition_or_measurement_approach":"10-year extended eGFR slope calculated from annual plasma creatinine values reported to NRR after year 3."}
• {"endpoint_text":"- Difference between groups in incidence of graft loss (assessed from NRR) up to 10 years after transplantation","definition_or_measurement_approach":"Incidence of graft loss assessed from NRR up to 10 years post-transplant."}
• {"endpoint_text":"- Difference between groups in incidence and time to cardiovascular events (from NRR, first of each type; coronary heart disease, cerebrovascular events, chronic heart failure) as assessed up to 10 years after transplantation","definition_or_measurement_approach":"Incidence and time-to-event for first cardiovascular events (coronary heart disease, cerebrovascular events, chronic heart failure) from NRR up to 10 years."}
• {"endpoint_text":"- Changes in urinary tubulus biomarkers from before to 72 weeks","definition_or_measurement_approach":"Change in urinary tubular biomarkers comparing baseline to 72 weeks."}
• {"endpoint_text":"- Difference between groups in urinary tubular function biomarker levels from before to 72 weeks of treatment (explorative endpoint)","definition_or_measurement_approach":"Urinary tubular function biomarker level changes baseline to 72 weeks (explorative)."}

Norway

Earliest CTIS Part Ii Submission Date

10-04-2024

Latest Decision Or Authorization Date

06-06-2024

Processing Time Days

57

Number Of Sites

1

Number Of Participants

330

Primary sponsor

Full Name

Oslo University Hospital HF

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Norway

Third parties

• {"country":"","full_name":"Norwegian Research Council","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"AstraZeneca","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"Norwegian Health Region South-East","duties_or_roles":"Monetary support","organisation_type":""}