Impact of dapagliflozin on vascular function in chronic kidney disease patients - (DAPA-VASC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire Rouen

Participant type

Pediatric, Patients

Age range

0-17 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

18 Oct 2022 → 31 Dec 2024

Decision date (initial)

2024-09-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-514887-14-00

EudraCT number

2021-002893-20

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To demonstrate that 12-week treatment with dapagliflozin improves endothelium-dependent flow-mediated dilatation of peripheral conduit arteries during short-term increase in blood flow in chronic kidney
disease patients

Secondary objectives 5

1. To demonstrate that 12-week treatment with dapagliflozin improves endothelium-dependent flow-mediated dilatation of peripheral conduit arteries during sustained increase in blood flow in chronic kidney disease patients
2. To demonstrate that 12-week treatment with dapagliflozin improves the bioavailability of endothelial vasodilating factors in chronic kidney disease patients
3. To demonstrate that 12-week treatment with dapagliflozin reduces oxidative stress and inflammation in chronic kidney disease patients
4. To demonstrate that 12-week treatment with dapagliflozin improves arterial stiffness and cardiovascular coupling in chronic kidney disease patients
5. To demonstrate that 12-week treatment with dapagliflozin improves cardiac function in chronic kidney disease patients

Conditions and MedDRA coding

chronic kidney disease patients

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Chronic kidney disease (eGFR ≥ 25 and ≤ 60 mL/min/1.73m² by CKD-EPI)
2. Age ≥ 18 years
3. Receiving a stable dose of an ACE inhibitor or ARB for at least 12 weeks before screening or patients who were documented to be unable to take angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs).
4. Patient having read and understood the information letter and signed the Informed Consent Form
5. For women: a. Women of childbearing potential : i. Effective contraception according to CTFG contraception recommendations (V1.1 21/09/2020) since at least 4 weeks before randomization and during treatment, and; ii. Negative blood pregnancy test; b. Women surgically sterile (absence of ovaries and/or uterus); c. Postmenopausal women (non-medically induced amenorrhea for at least 12 months prior to the inclusion visit). Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. Barrier methods must always be supplemented with the use of a spermicide.
6. Patient able to comply with the study protocol, in the investigator's judgment
7. Patient affiliated with, or beneficiary of a social security (health insurance) category.

Exclusion criteria 23

1. Type 1 and type 2 diabetes (fasting glycemia ≥ 126 mg/dL or use of oral hypoglycemic agents or insulin)
2. Patients whose conditions lead to reduced food absorption or severe dehydration
3. Patients with reduced insulin levels
4. Patients with increased insulin requirements due to an acute medical condition, surgery or excessive alcohol consumption
5. Recessive or autosomal dominant polycystic kidney disease
6. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
7. Lupus nephritis
8. Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment
9. History of organ transplantation
10. Body weight > 35 kg/m²
11. Receiving therapy with a sodium glucose co-transporter 2 (SGLT2) inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
12. Receiving phosphodiesterase type 5 inhibitors (sildenafil, tadalafil, vardenafil or other) or riociguat (due to the risk of hypotension potentiation with GTN spray).
13. Patients with NYHA class IV congestive heart failure at the time of enrolment
14. Myocardial infarction, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment
15. Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or valvular repair/replacement within 12 weeks prior to enrolment or is planned to undergo any of these procedures after randomization
16. Active malignancy requiring treatment at the time of enrolment or is planned to undergo any treatment after randomization
17. Severe hepatic impairment (Child-Pugh class C)
18. History of pancreatitis
19. History of frequent genital mycotic infections (> 2 during the last 12 months)
20. Current pregnancy OR women who are breast-feeding
21. Contraindications to NATISPRAY® 0.30mg/dose, solution for oral spray : - Hypersensitivity to nitrates or to any of the excipients, - State of shock, severe hypotension, - In combination with sildenafil, taladafil, vardenafil, avanafil and riociguat - Obstructive cardiomyopathy, - Inferior site myocardial infarction with extension to the right ventricle, acute phase, except when there is a sign of left ventricular failure, - Intracranial hypertension
22. Contra-indication to FORXIGA 10 mg film-coated tablets: hypersensitivity to dapagliflozin or to any of the excipients
23. Participation in another clinical study with an investigational product during the last 4 weeks prior to enrolment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in the magnitude of brachial artery flow-mediated dilatation in response to reactive hyperemia after 12-week treatment with dapagliflozin or placebo

Secondary endpoints 5

1. Change in the magnitude of radial artery flow-mediated dilatation in response to hand skin heating after 12-week treatment with dapagliflozin or placebo
2. Change in the plasma release of nitric oxide and epoxyeicosatrienoic acids induced by hand skin heating after 12-week treatment with dapagliflozin or placebo
3. Change in the plasma levels of pro-oxidant and pro-inflammatory lipid mediators 12-week treatment with dapagliflozin or placebo
4. Change in carotid artery elastic modulus, carotid-to-femoral pulse wave velocity and aortic augmentation index after 12-week treatment with dapagliflozin or placebo
5. Change in cardiac output, stroke volume, ejection fraction and left ventricular end-systolic elastance after 12-week treatment with dapagliflozin or placebo

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire Rouen

Sponsor organisation

Centre Hospitalier Universitaire Rouen

Address

1 Rue De Germont, Bp 96031 Bp 96031

City

Rouen Cedex

Postcode

76031

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire Rouen

Contact name

David MALLET

Public contact point

Organisation

Centre Hospitalier Universitaire Rouen

Contact name

David MALLET

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 8 files

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

Application history

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