Liver CirrhosisPhase 1DRAin-Em 01NCT05013502
Empagliflozin in Diuretic Refractory Ascites
A Phase 1 study testing Empagliflozin 10 MG in people with Liver Cirrhosis and Cirrhosis, run by Stanford University at 1 site in United States.
Trial summary
Ascites is the most frequent complication of liver cirrhosis and results in increased morbidity and mortality but current medical management options are limited. Here, the investigators will conduct an interventional single-arm pilot clinical trial toevaluate the feasibility of empagliflozin in managing… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Liver Cirrhosis, Cirrhosis, Ascites
- What is being tested?
- Empagliflozin 10 MG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Nov 2021to 30 Jun 2023
- Phase
- Phase 1
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Decompensated liver cirrhosis with ascites
- Diuretic-resistant ascites defined as one of the following: a) An inability to mobilize ascites despite adherence to dietary sodium restriction (2000 mg per day) and administration of maximum tolerable doses of oral diuretics; b) Rapid reaccumulation of fluid after therapeutic paracentesis despite adherence to a sodium-restricted diet. c) Development of diuretic-related complications such as progressive azotemia, hepatic encephalopathy, or progressive electrolyte imbalances
- Ability to understand and willingness to sign a written informed consent document
Who cannot join
- Hypersensitivity to any SGLT2 inhibitor
- Pregnant or breastfeeding women
- eGFR below 45mL/min/1.73m2 or decrease in eGFR by >30% between screening
- Recurrent urinary tract infections or recurrent genitourinary fungal infections, defined as > 2 infections in six months or >3 infections in one year
- Hypotension requiring oral vasopressor therapy
- Patients with particular risk for ketoacidosis including active moderate or severe alcohol use disorder, pancreatitis, pancreatic insulin deficiency from any cause, or episode of ketoacidosis in the past
- History of skin or soft tissue infection requiring IV antibiotics including Fornier's gangrene or prior limb amputation
- Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial subject or unlikely to complete the trial
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University Digestive Health Clinic
Redwood City, California, 94060
About this study
Official title: Management of Diuretic Refractory Ascites in Cirrhosis With Empagliflozin (DRAin-Em-01)
Ascites is the most frequent complication of liver cirrhosis and results in increased morbidity and mortality but current medical management options are limited. Here, the investigators will conduct an interventional single-arm pilot clinical trial toevaluate the feasibility of empagliflozin in managing diuretic-resistant ascites in patients with decompensated cirrhosis. This single site, open label pilot study will enroll participants with decompensated cirrhosis at a single site. Participants will receive empagliflozin 10mg oral tablets once daily for 12 weeks with monitoring for safety and adverse events.
Read the detailed description
Pharmacologic options for the management of ascites are limited to diuretics only. Each year approximately 10% of patients with cirrhosis develop diuretic-resistant ascites, necessitating the use of more invasive procedures such a paracentesis, transjugular intrahepatic portosystemic shunting (TIPS), and transplantation; each modality is associated with significant risks and limitations. Patients treated with diuretics may also develop complications such as acute kidney injury, encephalopathy, muscle cramping, or hyponatremia, limiting optimal dosages of these medications and hence, resulting in inadequate control of fluid retention. Thus, ascites that is resistant to our current therapies is an important unmet medical need.
Recently, SGLT2-Is have been shown to reduce heart failure hospitalizations and cardiovascular death in patients with and without diabetes in landmark, large-scale clinical trials. Empagliflozin improved heart failure outcomes without altering hemoglobin A1c or increasing risk of hypoglycemia in individuals without diabetes, suggesting that SGLT2-Is may act through a neurohormonal mechanism independent of blood glucose changes. Because cirrhosis and heart failure are disorders with a common pathophysiology of decreased effective arterial blood volume with resultant stimulation of the renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system, and total body fluid overload, the investigators hypothesize that SGLT2-Is may be effective in the management of ascites. Multiple lines of evidence suggest SGLT2-Is may have a beneficial role in chronic liver disease. Several case reports of patients with cirrhosis and diuretic-resistant ascites have found that SGLT2-I treatment was associated with near resolution of ascites and pedal edema. SGLT2-I treatment has also demonstrated improved hepatic function, reduction of fibrosis and normalization of liver enzymes in non-alcoholic fatty liver disease (NAFLD).Although SGLT2-I are partially cleared by the liver, empagliflozin is well tolerated in patients with cirrhosis. Thus, the investigators initiated a feasibility study to test the hypothesis that the SGLT2-I, empagliflozin, will decrease ascites by attenuating maladaptive neurohormonal and inflammatory responses in cirrhosis.
- Conditions
- Liver Cirrhosis, Cirrhosis, Ascites, Ascites Hepatic, Sodium-Glucose Transporter 2 Inhibitors
- Being tested
- Empagliflozin 10 MG
- Keywords
- diuretic refractory, diuretic resistant, empagliflozin
- Medical subject headings
- Liver Cirrhosis, Fibrosis, Ascites
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 10 MGDrug
empagliflozin 10mg PO once daily
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin 10mg PO daily for 12 weeks | Experimental | Single arm trial Receives: Drug: Empagliflozin 10 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participant retention rate as a measure of study feasibility
Retention rate and completion of trial activities through 12 weeks
Measured: Baseline to 12 weeks
Secondary outcomes (4)
Mean change in abdominal girth from baseline to 12 weeks
Abdominal girth as a measure of ascites volume
Measured: Baseline to 12 weeks
Mean change in body weight from baseline to 12 weeks
Body weight as a measure of ascites volume
Measured: Baseline to 12 weeks
Mean change in patient reported functional status
Functional status and quality of life measured on SF-36 questionnaire
Measured: Baseline to 12 weeks
Estimated glomerular filtration rate as a measure of kidney function
Change in renal function as measured by serum creatinine
Measured: Baseline to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2021
- Study start15 Nov 2021
- Primary completion30 May 2023
- Study completion30 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CirrhosisStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Aparna Goel, Stanford University
- Investigators
- Aparna Goel, MD, Principal investigator, Clinical Assistant Professor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05013502
- Sponsor's protocol ID
- IRB-61538
- Acronym
- DRAin-Em 01
- Status last verified
- Jul 2023
- First submitted
- 6 Aug 2021
- Last updated
- 2 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Management of Diuretic Refractory Ascites in Cirrhosis With Empagliflozin (DRAin-Em-01)
- ClinicalTrials.gov ID
- NCT05013502
- Acronym / sponsor ID
- DRAin-Em 01 / IRB-61538
- Conditions
- Liver Cirrhosis, Cirrhosis, Ascites, Ascites Hepatic, Sodium-Glucose Transporter 2 Inhibitors
- Keywords
- diuretic refractory, diuretic resistant, empagliflozin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 15 Nov 2021 (actual)
- Primary completion
- 30 May 2023 (actual)
- Study completion
- 30 Jun 2023 (actual)
- First posted
- 19 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.
Ascites is the most frequent complication of liver cirrhosis and results in increased morbidity and mortality but current medical management options are limited. Here, the investigators will conduct an interventional single-arm pilot clinical trial toevaluate the feasibility of empagliflozin in managing diuretic-resistant ascites in patients with decompensated cirrhosis. This single site, open label pilot study will enroll participants with decompensated cirrhosis at a single site. Participants will receive empagliflozin 10mg oral tablets once daily for 12 weeks with monitoring for safety and adverse events.
Detailed description
Pharmacologic options for the management of ascites are limited to diuretics only. Each year approximately 10% of patients with cirrhosis develop diuretic-resistant ascites, necessitating the use of more invasive procedures such a paracentesis, transjugular intrahepatic portosystemic shunting (TIPS), and transplantation; each modality is associated with significant risks and limitations. Patients treated with diuretics may also develop complications such as acute kidney injury, encephalopathy, muscle cramping, or hyponatremia, limiting optimal dosages of these medications and hence, resulting in inadequate control of fluid retention. Thus, ascites that is resistant to our current therapies is an important unmet medical need.
Recently, SGLT2-Is have been shown to reduce heart failure hospitalizations and cardiovascular death in patients with and without diabetes in landmark, large-scale clinical trials. Empagliflozin improved heart failure outcomes without altering hemoglobin A1c or increasing risk of hypoglycemia in individuals without diabetes, suggesting that SGLT2-Is may act through a neurohormonal mechanism independent of blood glucose changes. Because cirrhosis and heart failure are disorders with a common pathophysiology of decreased effective arterial blood volume with resultant stimulation of the renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system, and total body fluid overload, the investigators hypothesize that SGLT2-Is may be effective in the management of ascites. Multiple lines of evidence suggest SGLT2-Is may have a beneficial role in chronic liver disease. Several case reports of patients with cirrhosis and diuretic-resistant ascites have found that SGLT2-I treatment was associated with near resolution of ascites and pedal edema. SGLT2-I treatment has also demonstrated improved hepatic function, reduction of fibrosis and normalization of liver enzymes in non-alcoholic fatty liver disease (NAFLD).Although SGLT2-I are partially cleared by the liver, empagliflozin is well tolerated in patients with cirrhosis. Thus, the investigators initiated a feasibility study to test the hypothesis that the SGLT2-I, empagliflozin, will decrease ascites by attenuating maladaptive neurohormonal and inflammatory responses in cirrhosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin 10mg PO daily for 12 weeks | Experimental | Drug: Empagliflozin 10 MGSingle arm trial |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Decompensated liver cirrhosis with ascites
- Diuretic-resistant ascites defined as one of the following: a) An inability to mobilize ascites despite adherence to dietary sodium restriction (2000 mg per day) and administration of maximum tolerable doses of oral diuretics; b) Rapid reaccumulation of fluid after therapeutic paracentesis despite adherence to a sodium-restricted diet. c) Development of diuretic-related complications such as progressive azotemia, hepatic encephalopathy, or progressive electrolyte imbalances
- Ability to understand and willingness to sign a written informed consent document
Key exclusion criteria (8 listed)
- Hypersensitivity to any SGLT2 inhibitor
- Pregnant or breastfeeding women
- eGFR below 45mL/min/1.73m2 or decrease in eGFR by >30% between screening
- Recurrent urinary tract infections or recurrent genitourinary fungal infections, defined as > 2 infections in six months or >3 infections in one year
- Hypotension requiring oral vasopressor therapy
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 |
|---|---|---|
| Empagliflozin 10 MGempagliflozin 10mg PO once daily | Drug | Empagliflozin 10mg PO daily for 12 weeks |
Primary outcome
Participant retention rate as a measure of study feasibility
Time frame: Baseline to 12 weeks
Retention rate and completion of trial activities through 12 weeks
4 secondary outcomes
Mean change in abdominal girth from baseline to 12 weeks
Time frame: Baseline to 12 weeks
Mean change in body weight from baseline to 12 weeks
Time frame: Baseline to 12 weeks
Mean change in patient reported functional status
Time frame: Baseline to 12 weeks
Estimated glomerular filtration rate as a measure of kidney function
Time frame: Baseline to 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2023.
- Individual participant dataSharing planned: No
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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.
Aparna Goel, MD principal investigator
Clinical Assistant Professor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Empagliflozin 10 MG in people with Liver Cirrhosis and Cirrhosis, run by Stanford University at 1 site in United States.
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 8 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: finished, as of the sponsor's last update on 2 Aug 2023. 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 United States. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Participant retention rate as a measure of study feasibility (time frame: Baseline to 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Aug 2023.