Evolution of proteinuria in renal transplant patients treated with Dapagliflozin

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Montpellier

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Reproductive and Urinary Physiological Phenomena [G08]

Trial duration

27 Dec 2023 → 28 Oct 2025

Decision date (initial)

2023-10-13

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

University Hospital of Montpellier

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic

Estimate the rate of patients, treated with Dapagliflozin, with a nephroprotective effect at 6 months after dapagliflozin initiation

Secondary objectives 3

1. Evaluate the effect of dapagliflozin on metabolic complications : diabetes, hypertension, dyslipidemia
2. Evaluate the side effects related to dapagliflozin
3. Compare the evolution of proteinuria in proteinuric CKD kidney transplant patients with a control group of non-transplant proteinuric CKD patients treated with Dapagliflozin in the same indication

Conditions and MedDRA coding

chronic renal failure

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Initiation of dapagliflozin less than 14 days ago for chronic kidney disease
2. eGFR (by CKD-EPI) between 25 and 75 ml.min.1.73m²
3. Albuminuria/Creatinuria ratio between 200 mg/g and 5000 mg/g
4. Treatment with an ACE inhibitor or angiotensin 2 receptor blocker (ARA II or sartan) at the maximum tolerated dose for at least 4 weeks
5. Age ≥ 18 years
6. For CKD Renal Transplant Recipients: kidney transplant more than one year

Exclusion criteria 12

1. Guardianship or trusteeship
2. Patient protected by law
3. Subject not affiliated to a social security scheme, or not benefiting from such a scheme
4. Patient deprived of liberty
5. For the control group (non-transplanted CKD) : history of transplantation
6. Initiation or modification of immunosuppressive therapy less than 6 months ago (except temporary discontinuation for infection or change in dosage)
7. Type 1 diabetes
8. Severe liver failure (Child-Pugh stage C)
9. Intolerance to any of the excipients of Forxiga®, in particular lactose intolerance
10. Patient undergoing treatment with another SGLT2 inhibitor (sodium-glucose co-transporter type 2)
11. Patient enrolled in another clinical trial
12. Pregnancy or breast-feeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Decrease in albuminuria/creatinuria ratio ≥ 50% from baseline or achievement of albuminuria/creatinuria ratio ≤ 30 mg/g at 6 months after introduction of dapagliflozin

Secondary endpoints 11

1. Decrease in albuminuria/creatinuria ratio ≥ 50% from baseline or achievement of albuminuria/creatinuria ratio ≤ 30 mg/g, 3 months after introduction of dapagliflozin
2. Decrease ≥ 50% in GFR from baseline to M3 et M6
3. Number of patients with end-stage CKD as defined by dialysis or pre-emptive transplant replacement therapy at M6
4. Numbers of episodes of acute renal failure defined according to KDIGO criteria (stage I: increase in serum creatinine ≥ 26.52 micromoles/L in 48 hours or increase in serum creatinine of ≥ 1.5 times the initial value in the preceding 7 days, stage II: increase in serum creatinine ≥ 2 times the initial value, stage III: increase in serum creatinine ≥ 3 times the initial value or serum creatinine ≥ 353. 6 mmol/l or need to start extrarenal purification at M3 and M6
5. Death rate from any cause
6. Study of interaction with immunosuppressive treatments (residual rate and change in dosage of immunosuppressive treatment) at M3 and M6
7. Changes in blood pressure, weight and Hba1c from baseline to M3 et M6
8. Occurrence of infectious side effects, including urinary tract infections, genital mycotic infections, Fournier's gangrene at M3 and M6
9. Occurrence of metabolic side effects including diabetic ketoacidosis, hypoglycemia, dehydration, hypotension, hydrosodium depletion at M3 and M6
10. Other adverse reactions associated with dapagliflozin at M3 and M6
11. Discontinuation of treatment for side effects at M3 and M6

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Montpellier

Sponsor organisation

Centre Hospitalier Universitaire De Montpellier

Address

191 Avenue Du Doyen Gaston Giraud

City

Montpellier Cedex 5

Postcode

34295

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Montpellier

Contact name

Amelle ISSA

Public contact point

Organisation

Centre Hospitalier Universitaire De Montpellier

Contact name

Amelle ISSA

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications