CirrhosisPhase 2NCT05014594
Sodium-glucose Linked Transporter 2 (SGLT-2) Inhibitors in Recurrent Ascites: a Pilot RCT
A Phase 2 study testing Dapagliflozin (10Mg Tab) along with standard medical therapy in people with Cirrhosis and Ascites Hepatic, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
Trial summary
The development of ascites is a landmark event in the natural history of cirrhosis and signifies a grim prognosis. Portal hypertension and splanchnic arterial vasodilatation are the major contributors in the development of ascites. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Cirrhosis, Ascites Hepatic
- What is being tested?
- Dapagliflozin (10Mg Tab) along with standard medical therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteIndia
- Study dates
- 3 Sep 2021to 19 May 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-70 years
- Cirrhosis as determined by clinical findings, hemogram and liver function tests, endoscopic findings and imaging
- Recurrent ascites: Recurrent ascites will be defined as tense ascites recurring at least thrice within the last 1-year despite optimal standard medical treatment including large volume paracentesis and diuretics
Who cannot join
- Presence of chronic kidney disease as defined by an estimated glomerular filtration rate of <60 ml/min for more than 3 months. The MDRD-6 equation will be used for estimating GFR.
- Portal vein thrombosis
- Hepatocellular carcinoma.
- Gastrointestinal bleed in the preceding 2-weeks
- Overt hepatic encephalopathy in the preceding 1-month
- Documented hypoglycemia in the preceding 1-month
Show all 18Show fewer
- Serum sodium < 125 meq/l
- History of skeletal fracture in the preceding year or any past history of fragility fracture
- History of peripheral vascular disease
- Acute kidney injury as defined by the International Club of Ascites criteria
- Infection within 1-month preceding the study
- Anatomic urologic defects that predispose to urinary tract infection
- Mixed ascites (additional etiology of ascites apart from portal hypertension)
- Any severe extra hepatic condition including respiratory and cardiac failure
- Acute-on-chronic liver failure as per the APASL or CANONIC criteria
- Treatment with drug with known effects on systemic and renal hemodynamics within 7 days of inclusion excepting beta-blockers
- Patients opting for liver transplant or TIPS
- Refusal to give consent
Trial locations and contacts
1 site in 1 country.
India1 site, 1 recruiting
- Recruiting
Dept of Hepatology, PGIMER
Chandigarh, 160012
Virendra Singh, MD, DM, +911722756338, virendrasingh100@hotmail.com
About this study
The development of ascites is a landmark event in the natural history of cirrhosis and signifies a grim prognosis. Portal hypertension and splanchnic arterial vasodilatation are the major contributors in the development of ascites. Vasodilatation with the consequential decrease in effective circulating volume leads to the activation of sympathetic nervous system and renin angiotensin aldosterone system (RAAS), leading to antinatriuretic effects and retention of sodium and water. This results in the formation of ascites. Management of ascites primarily consists of salt restrictrion and diuretics. Liver transplant is the ultimate panacea.
Dapaglifozin, a Sodium glucose linked transporter-2(SGLT-2) inhibitor, is a part of the routine armamentarium for treatment of patients with Diabetes Mellitus type-2. Its safety is well established in non-diabetic patients too where it has been shown to improve cardiovascular outcomes. The risk of hypoglycemia is negligible as its action is independent of insulin. By virtue of its natriuretic effect, it has been shown to reduce hospitalisations in patients with heart failure irrespective of the presence of diabetes. We hypothesise that a similar natriuretic effect may help in suppressing the renin-angiotensin axis with improved mobilization of ascites in patients with cirrhosis. Pharmacokinetic data on the use of Dapaglifozin suggest that there is no need for dose modification in cirrhosis. The AUC and Cmax for Dapaglifozin in Child Pugh C cirrhosis is 67% and 40%, respectively. In a recent small case series, SGLT-2 inhibitors including dapaglifozin led to improvement in fluid retention and serum sodium, without acute kidney injury or encephalopathy, in patients with cirrhosis. However, SGLT-2 inhibitors have not been evaluated in randomized controlled trials. In this pilot study, we plan to evaluate the efficacy and safety of dapaglifozin in cirrhotics patients with recurrent ascites.
- Conditions
- Cirrhosis, Ascites Hepatic
- Being tested
- Dapagliflozin (10Mg Tab) along with standard medical therapy, Placebo of dapaglifozin along with standard medical therapy
- Medical subject headings
- Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapagliflozin (10Mg Tab) along with standard medical therapyDrug
Oral Dapaglifozin (10 mg/day) along with standard medical therapy will be given to Group A while a placebo of dapaglifozin along with standard medical therapy will be used in Group B
Placebo of dapaglifozin along with standard medical therapyDrug
Standard medical therapy will include dietary restriction of sodium, treatment with diuretics, repeated LVP as needed and other supportive care. Patients on non-selective beta blockers will continue to do so with dose modifications/withdrawal as per Baveno VI guidelines.
| Study group | Role | What they receive |
|---|---|---|
| Group A (Dapaglifozin) | Active comparator | Group A will receive oral Dapaglifozin (10 mg/day) along with standard medical therapy for 6 months Receives: Drug: Dapagliflozin (10Mg Tab) along with standard medical therapy |
| Group B (Placebo) | Placebo comparator | Group B will receive placebo of Dapaglifozin along with standard medical therapy for 6 months Receives: Drug: Placebo of dapaglifozin along with standard medical therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
control of ascites at 6-months
Control of ascites will be defined as follows-
- Complete response will be total absence of ascites.
- Partial response as presence of ascites not requiring paracentesis
- Non response will be defined as persistence of severe ascites requiring paracentesis.
Measured: 6 months
Secondary outcomes (20)
Change in eGFR measured by MDRD-6 at 3 months and 6 months
eGFR will be measured by MDRD-6 formula
Measured: 6 months
Change in urine output at 2-weeks, 3-months and 6-months
Change in 24-hour urine output (ml) at 6-months
Measured: 6-months
Change in serum sodium (mEq/l) at 2-weeks, 3-months and 6 months
Change in serum sodium (mEq/l)
Measured: 6 months
Change in 24-hours urinary sodium (mEq) at 2 weeks, 3 months and 6 months
Change in 24-hours urinary sodium (mEq)
Measured: 6 months
Change in HbA1c at 3 and 6 months
Change in HbA1c
Measured: 6 months
Change in Child-Turcotte-Pugh (CTP) score at 3 months and 6 months
Change in CTP score. The CTP score incorporates the variables of serum bilirubin, albumin, prothrombin time-INR, grade of ascites and hepatic encephalopathy. The score ranges from 5-15 and a higher score portends a worse prognosis
Measured: 6 months
Change in model for end stage liver disease (MELD) score at 3 months and 6 months
Change in MELD score. The MELD score incorporates the variables of serum bilirubin, creatinine and Internation Normalised Ratio (INR). Higher MELD score indicates worse prognosis
Measured: 6 months
Incidence of spontaneous bacterial peritonitis (SBP), urinary tract infection (UTI) and other infections
The diagnosis of SBP will be based on neutrophil count in ascitic fluid of >250/mm3 as determined by microscopy and positive ascitic fluid culture or >250 /mm3 with negative culture called as culture negative neutrocytic ascites.Other infections will be diagnosed as per CDC criteria.
Measured: 6 months
Incidence of overt hepatic encephalopathy over 6-months
Over hepatic encephalopathy (HE) will be defined as grade II or higher HE as per the West haven classification
Measured: 6 months
Incidence of acute kidney injury over 6-months
Acute kidney injury will be defined as per the International Club of Ascites criteria
Measured: 6 months
Incidence of Hyponatremia (serum sodium <130 meq/L), hypokalemia (Serum potassium < 3.5 meq/L), hyperkalemia (Serum potassium >6meq/L) over 6-months.
Hyponatremia: serum sodium <130 meq/L hypokalemia: serum potassium < 3.5 meq/L hyperkalemia: serum potassium >6meq/L)
Measured: 6 months
Incidence of skeletal fractures over 6-months
Incidence of skeletal fractures over 6-months
Measured: 6 months
Change in bone densitometry as assessed by DEXA at 6-months
Bone densitometry will be assessed by DEXA
Measured: 6 months
Incidence of diabetic ketoacidosis or hyperglycemic hyperosmolar nonketotic coma over 6-months
Incidence of diabetic ketoacidosis or hyperglycemic hyperosmolar nonketotic coma over 6-months
Measured: 6 months
Incidence of hepatocellular carcinoma over 6-months
Hepatocellular carcinoma will be diagnosed based on imaging findings and AFP
Measured: 6 months
Changes in plasma renin activity and aldosterone levels at 6- months
Changes in plasma renin activity (ng/ml/hr) and aldosterone (ng/dL) levels at 6- months
Measured: 6 months
Frequency and volume of LVP over 6-months.
Frequency and volume of ascitic fluid removed (in litres) over 6-months.
Measured: 6 months
Survival at 6-months
Survival at 6-months after start of therapy
Measured: Survival at 6-months
Safety of dapaglifozin as assessed by adverse effects
Safety of dapaglifozin as assessed by adverse effects
Measured: 6 months
Renal resistive index at 6 months
Renal resistive index will be measured using ultrasound doppler interrogation of intrarenal arteries using formula (peak systolic velocity - end-diastolic velocity) / peak systolic velocity
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2021
- Study start3 Sep 2021
- Primary completion19 May 2022 (estimated)
- Study completion19 May 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr.Virendra Singh, Post Graduate Institute of Medical Education and Research, Chandigarh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05014594
- Sponsor's protocol ID
- Dapa recurrent ascites
- Status last verified
- Sep 2021
- First submitted
- 14 Aug 2021
- Last updated
- 5 Sep 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Singh V, De A, Aggrawal R, Singh A, Charak S, Bhagat N. Safety and Efficacy of Dapagliflozin in Recurrent Ascites: A Pilot Study. Dig Dis Sci. 2025 Feb;70(2):835-842. doi: 10.1007/s10620-024-08667-4. Epub 2024 Oct 9.
PubMed 39384712
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sodium-glucose Linked Transporter 2 (SGLT-2) Inhibitors in Recurrent Ascites: a Pilot RCT
- ClinicalTrials.gov ID
- NCT05014594
- Acronym / sponsor ID
- Dapa recurrent ascites
- Conditions
- Cirrhosis, Ascites Hepatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- 3 Sep 2021 (actual)
- Primary completion
- 19 May 2022 (estimated)
- Study completion
- 19 May 2022 (estimated)
- First posted
- 20 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The development of ascites is a landmark event in the natural history of cirrhosis and signifies a grim prognosis. Portal hypertension and splanchnic arterial vasodilatation are the major contributors in the development of ascites. Vasodilatation with the consequential decrease in effective circulating volume leads to the activation of sympathetic nervous system and renin angiotensin aldosterone system (RAAS), leading to antinatriuretic effects and retention of sodium and water. This results in the formation of ascites. Management of ascites primarily consists of salt restrictrion and diuretics. Liver transplant is the ultimate panacea.
Dapaglifozin, a Sodium glucose linked transporter-2(SGLT-2) inhibitor, is a part of the routine armamentarium for treatment of patients with Diabetes Mellitus type-2. Its safety is well established in non-diabetic patients too where it has been shown to improve cardiovascular outcomes. The risk of hypoglycemia is negligible as its action is independent of insulin. By virtue of its natriuretic effect, it has been shown to reduce hospitalisations in patients with heart failure irrespective of the presence of diabetes. We hypothesise that a similar natriuretic effect may help in suppressing the renin-angiotensin axis with improved mobilization of ascites in patients with cirrhosis. Pharmacokinetic data on the use of Dapaglifozin suggest that there is no need for dose modification in cirrhosis. The AUC and Cmax for Dapaglifozin in Child Pugh C cirrhosis is 67% and 40%, respectively. In a recent small case series, SGLT-2 inhibitors including dapaglifozin led to improvement in fluid retention and serum sodium, without acute kidney injury or encephalopathy, in patients with cirrhosis. However, SGLT-2 inhibitors have not been evaluated in randomized controlled trials. In this pilot study, we plan to evaluate the efficacy and safety of dapaglifozin in cirrhotics patients with recurrent ascites.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A (Dapaglifozin) | Active comparator | Drug: Dapagliflozin (10Mg Tab) along with standard medical therapyGroup A will receive oral Dapaglifozin (10 mg/day) along with standard medical therapy for 6 months |
| Group B (Placebo) | Placebo comparator | Drug: Placebo of dapaglifozin along with standard medical therapyGroup B will receive placebo of Dapaglifozin along with standard medical therapy for 6 months |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age 18-70 years
- Cirrhosis as determined by clinical findings, hemogram and liver function tests, endoscopic findings and imaging
- Recurrent ascites: Recurrent ascites will be defined as tense ascites recurring at least thrice within the last 1-year despite optimal standard medical treatment including large volume paracentesis and diuretics
Key exclusion criteria (18 listed)
- Presence of chronic kidney disease as defined by an estimated glomerular filtration rate of <60 ml/min for more than 3 months. The MDRD-6 equation will be used for estimating GFR.
- Portal vein thrombosis
- Hepatocellular carcinoma.
- Gastrointestinal bleed in the preceding 2-weeks
- Overt hepatic encephalopathy in the preceding 1-month
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dapagliflozin (10Mg Tab) along with standard medical therapyOral Dapaglifozin (10 mg/day) along with standard medical therapy will be given to Group A while a placebo of dapaglifozin along with standard medical therapy will be used in Group B | Drug | Group A (Dapaglifozin) |
| Placebo of dapaglifozin along with standard medical therapyStandard medical therapy will include dietary restriction of sodium, treatment with diuretics, repeated LVP as needed and other supportive care. Patients on non-selective beta blockers will continue to do so with dose modifications/withdrawal as per Baveno VI guidelines. | Drug | Group B (Placebo) |
Primary outcome
control of ascites at 6-months
Time frame: 6 months
Control of ascites will be defined as follows- * Complete response will be total absence of ascites. * Partial response as presence of ascites not requiring paracentesis * Non response will be defined as persistence of severe ascites requiring paracentesis.
20 secondary outcomes
Change in eGFR measured by MDRD-6 at 3 months and 6 months
Time frame: 6 months
Change in urine output at 2-weeks, 3-months and 6-months
Time frame: 6-months
Change in serum sodium (mEq/l) at 2-weeks, 3-months and 6 months
Time frame: 6 months
Change in 24-hours urinary sodium (mEq) at 2 weeks, 3 months and 6 months
Time frame: 6 months
Change in HbA1c at 3 and 6 months
Time frame: 6 months
Change in Child-Turcotte-Pugh (CTP) score at 3 months and 6 months
Time frame: 6 months
Change in model for end stage liver disease (MELD) score at 3 months and 6 months
Time frame: 6 months
Incidence of spontaneous bacterial peritonitis (SBP), urinary tract infection (UTI) and other infections
Time frame: 6 months
Incidence of overt hepatic encephalopathy over 6-months
Time frame: 6 months
Incidence of acute kidney injury over 6-months
Time frame: 6 months
Incidence of Hyponatremia (serum sodium <130 meq/L), hypokalemia (Serum potassium < 3.5 meq/L), hyperkalemia (Serum potassium >6meq/L) over 6-months.
Time frame: 6 months
Incidence of skeletal fractures over 6-months
Time frame: 6 months
Change in bone densitometry as assessed by DEXA at 6-months
Time frame: 6 months
Incidence of diabetic ketoacidosis or hyperglycemic hyperosmolar nonketotic coma over 6-months
Time frame: 6 months
Incidence of hepatocellular carcinoma over 6-months
Time frame: 6 months
Changes in plasma renin activity and aldosterone levels at 6- months
Time frame: 6 months
Frequency and volume of LVP over 6-months.
Time frame: 6 months
Survival at 6-months
Time frame: Survival at 6-months
Safety of dapaglifozin as assessed by adverse effects
Time frame: 6 months
Renal resistive index at 6 months
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2021.
- Derived from this study: PubMed 39384712Singh V, De A, Aggrawal R, Singh A, Charak S, Bhagat N. Safety and Efficacy of Dapagliflozin in Recurrent Ascites: A Pilot Study. Dig Dis Sci. 2025 Feb;70(2):835-842. doi: 10.1007/s10620-024-08667-4. Epub 2024 Oct 9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dapagliflozin (10Mg Tab) along with standard medical therapy in people with Cirrhosis and Ascites Hepatic, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Virendra Singh, MD,DM,FASGE (0172-275-6338, virendrasingh100@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
control of ascites at 6-months (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05014594, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2021; AzTrials last refreshed its copy on 7 Nov 2026.