Dapagliflozin in the treatment of decompensated liver cirrhosis: phase IIb randomised, controlled clinical trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Ospedale-Universita Padova

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

28 Jul 2025 → ongoing

Decision date (initial)

2024-06-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Italian Ministry of Health

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

The primary objective of the study will be to evaluate the safety of dapagliflozin versus standard medical therapy in patients with decompensated liver cirrhosis.

Secondary objectives 5

1. To evaluate signs of clinical effectiveness of dapagliflozin versus standard medical therapy treatment
2. Evaluate effect of dapagliflozin versus standard medical therapy on patients' quality of life
3. To evaluate effect of intervention on biomarkers of systemic inflammation
4. to evaluate the effect of intervention on biomarkers of circulatory dysfunction
5. To assess the effect of intervention on biomarkers of oxidative stress

Conditions and MedDRA coding

Decompensated liver cirrhosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Age between 18 and 85 years
2. Diagnosis of liver cirrhosis, documented on the basis of histological examination and/or clinical and/or instrumental examinations (ultrasonography, CT scan or liver elastography > 15 kPa)
3. Liver cirrhosis decompensation (overt hepatic encephalopathy, clinically significant ascites, hemorrhage from esophageal varices) developed within the past 12 months

Exclusion criteria 21

1. Established hypersensitivity to Dapaglifozin
2. Ongoing therapy with SGLT2 inhibitors (Dapagliflozin, Empagliflozin, Canagliflozin, Ertugliflozin etc)
3. Pregnancy or breastfeeding (in the case of women of childbearing age, they will be asked to maintain effective contraception or, alternatively, abstention from sexual intercourse during the observation period)
4. Hepatocarcinoma outside the Milan criteria (a single nodule<5 cm or multiple nodules [maximum 3], the largest of which ≤3 cm)
5. Active extrahepatic malignancy
6. Chronic kidney disease with estimated VFG < 30 ml/min/1.73m2
7. Other known extrahepatic diseases of severe grade (e.g., heart failure NYHA class ≥ 3; COPD GOLD class ≥ 3; psychiatric disorders);
8. Diagnosis oftype 1 Diabetes Mellitus and/or previous history of diabetic ketoacidosis
9. Ascites refractory to diuretic therapy according to International Club of Ascites criteria
10. Patient who is a carrier of TIPS
11. Active therapy for HCV eradication with Direct Antiviral Agents or terminated < 6 months before
12. Therapy for HBV suppression with nucleoside/nucleotide analogs started < 6 months before
13. Active alcohol consumption greater than 21 weekly alcohol units
14. Presence of at least one episode of acute kidney injury (AKI) in the 4 weeks prior to enrollment
15. Presence of two or more episodes of urinary tract infection in the 12 months prior to enrollment
16. Presence of >2 episodes of "overt" hepatic encephalopathy in the 12 months prior to enrollment
17. Body mass index (BMI) < 20 kg/m^2
18. History of prior solid organ transplantation
19. Inclusion in other clinical trials in the month prior to study initiation
20. Presence of mental incapacity, complete language barrier, poor social support, or other reasons that, in the opinion of the investigator, may preclude the proper conduct of the study
21. Refusal or inability to sign informed consent and absence of a legal guardian capable of signing consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of global adverse events and incidence of serious adverse events.

Secondary endpoints 22

1. Composite endpoints of further decompensation of cirrhosis (occurrence of variceal bleeding, hepatic encephalopathy, new-onset ascites or recurrent ascites, hepatorenal syndrome, spontaneous bacterial peritonitis) and death assessed at day 28 (± 7), 56 (± 7), 84 (± 7), 112 (± 7), 140 (± 7), and 168 (± 7)
2. Incidence of new onset ascites
3. Incidence of recurrent ascites
4. Incidence of hepatic encephalopathy
5. Incidence of variceal bleeding
6. Incidence of hepatorenal syndrome
7. Incdencde of spontaneous bacterial peritonitis
8. Change from baseline in MELD score, MELD-Na score, and Child-Pugh score at day 28 (± 7), 56 (± 7), 84 (± 7), 112 (± 7), 140 (± 7), and 168 (± 7)
9. Change in EQ-5D quality of life questionnaire score at day 84 (± 7) and 168 (± 7)
10. Change in Liver Frailty index at day 28 (± 7), 56 (± 7), 84 (± 7), 112 (± 7), 140 (± 7) and 168 (± 7)
11. Change from baseline in creatinine and estimated glomerular filtrate values at day 28 (± 7), 56 (± 7), 84 (± 7), 112 (± 7), 140 (± 7) and 168 (± 7)
12. Incidence of acute over chronic liver failure
13. Change from baseline in 24-hour sodiuria at day 28 (± 7), day 84 (± 7) and 168 (± 7).
14. Change from baseline in body weight at day 28 (± 7), 56 (± 7), 84 (± 7), 112 (± 7), 140 (± 7) and 168 (± 7).
15. Change from baseline in proinflammatory cytokines (IL1beta, IL6, IL8, IL10, TNF-alpha, IL1ra) at day 84 (± 7) and 168 (± 7).
16. Change from baseline in markers of circulatory dysfunction (renin, aldosterone, copeptin) at day 84 (± 7) and 168 (± 7).
17. Change from baseline in markers of oxidative stress (oxidized albumin isoforms HNA1 and HNA2, thiobarbituric acid reactive substance assay) at day 84 (± 7) and 168 (± 7).
18. Change from baseline in markers of endothelial dysfunction (von Willebrand factor) at day 84 (± 7) and 168 (± 7).
19. Change from baseline in markers of liver fibrosis (PRO-C3, PRO-C6) at day 84 (± 7) and 168 (± 7),
20. Change from baseline in biomarkers of bacterial translocation (lipopolysaccharide binding protein, LBP) at day 84 (± 7) and 168 (± 7)
21. Change from baseline of "DAMPs" biomarkers (mitochondrial DNA, HMGB1) at day 84 (± 7) and 168 (± 7)
22. Change from baseline in metabolites measured by untargeted metabolomics at day 84 (± 7) and 168 (± 7)

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedale-Universita Padova

Sponsor organisation

Azienda Ospedale-Universita Padova

Address

Via Nicolo' Giustiniani 2

City

Padova

Postcode

35128

Country

Italy

Scientific contact point

Organisation

Azienda Ospedale-Universita Padova

Contact name

Salvatore Silvio Piano

Public contact point

Organisation

Azienda Ospedale-Universita Padova

Contact name

Salvatore Silvio Piano

Locations

1 EU/EEA country · 3 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 6 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