Refractory AscitesPhase 3NCT04621617
Midodrine and Albumin in Patients With Refractory Ascites
A Phase 3 study testing Albumin, Midodrine and Standard medical therapy (SMT) in people with Refractory Ascites, run by Post Graduate Institute of Medical Education and Research, Chandigarh.
Trial summary
Refractory ascites is seen in 5-10% of patients with cirrhosis.Decompensated cirrhosis with refractory ascites has a mortality rate of around 40% in a year and a median survival of 6 months.Portal hypertension and splanchnic vasodilation are major factors in the development of ascites.The treatment of refractory… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Refractory Ascites
- What is being tested?
- Albumin, Midodrine and Standard medical therapy (SMT)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 114 participants
- Where
- No sites listed yet
- Study dates
- Nov 2020to Apr 2022
- Phase
- Phase 3
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 18 and 80 years
- Refractory ascites in cirrhosis of any etiology
Who cannot join
- Mixed ascites: cirrhosis plus another cause of ascites
- Gastrointestinal bleed within 7 days of enrolment.
- Presence of hepatorenal syndrome
- Hepatic encephalopathy grade 2 or higher
- Infection within 1 month preceding the study
- Cardiovascular disease (ejection fraction < 35% or abnormal ECG) or arterial hypertension (BP > 140/90 mm of Hg)
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- Abnormal urine analysis with proteinuria > 500 mg/24 hour or 50 red blood cells/high power field, or granular casts or ultrasonographic evidence of intrinsic renal disease
- Presence of hepatocellular carcinoma or portal vein thrombosis
- Treatment with drug with known effects on systemic and renal hemodynamics within 7 days of inclusion excepting beta-blockers
- Patient not willing for study.
- Patient opting for liver transplantation/ transjugular intrahepatic portosystemic shunt
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Midodrine and Albumin in Patients With Refractory Ascites. A Randomised Controlled Trial.
Refractory ascites is seen in 5-10% of patients with cirrhosis.Decompensated cirrhosis with refractory ascites has a mortality rate of around 40% in a year and a median survival of 6 months.Portal hypertension and splanchnic vasodilation are major factors in the development of ascites.The treatment of refractory ascites involves salt restriction, diuretics, large volume paracentesis (LVP), transjugular Intrahepatic Portosystemic shunt (TIPS) and Liver Transplantation (LT). Currently the only curative treatment is LT. However, LT is limited due to organ shortage and high cost.
Long-term human albumin (HA) administration in patients with uncomplicated and refractory ascites, has shown to improve survival or delay the complications of cirrhosis. Midodrine, an oral α1- adrenergic agonist has been used in refractory ascites with variable results. However, there is no study on the use of long term Midodrine and HA in patients with refractory ascites. Therefore, we plan to study the effect of long term midodrine and HA in patients with refractory ascites.
- Conditions
- Refractory Ascites
- Being tested
- Albumin, Midodrine, Standard medical therapy (SMT)
- Medical subject headings
- Ascites
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlbuminDrug
Human albumin will be administered by intravenous infusion at a dose of 1.5 gm/kg/week for 2 weeks followed by HA 40 grams every 7days
MidodrineDrug
Oral Midodrine will be given at a dose of 7.5 mg three times in a day
Standard medical therapy (SMT)Drug
SMT will include nutritional support, rifaximin, lactulose or lactitol, diuretics, SBP prophylaxis with norfloxacin, restriction of sodium, multivitamins, and other supportive measures as deemed necessary. LVP will be done as needed. 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 |
|---|---|---|
| Albumin + Midodrine + SMT | Active comparator | Human albumin plus oral midodrine Receives: Drug: Albumin; Drug: Midodrine; Drug: Standard medical therapy (SMT) |
| Albumin + SMT | Active comparator | Human albumin plus placebo of midodrine Receives: Drug: Albumin; Drug: Standard medical therapy (SMT) |
| SMT | Placebo comparator | standard medical therapy plus placebo of midodrine Receives: Drug: Standard medical therapy (SMT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with control of ascites at 1 year
Control of ascites will be defined as-
- 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: 1 year
Secondary outcomes (11)
Change in estimated glomerular filtration rate (eGFR) measured by modified diet in renal disease 6 (MDRD6) formula at 3 months intervals
eGFR will be measured using MDRD6 formula
Measured: 1 year
Changes in concentration of albumin at 3 months intervals
Change in concentration of serum albumin (g/dl)
Measured: 1 year
Change in model for end stage liver disease (MELD) score
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: 1 year
Change in mean arterial pressure at 3 months interval
Change in mean arterial pressure (mm of Hg) will be noted
Measured: 1 year
Changes in serum and 24- hour urine sodium
Serum and urine sodium concentration will be measured in meq/L
Measured: 1 year
Incidence of spontaneous bacterial peritonitis (SBP) 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.20 Other infections will be diagnosed as per CDC criteria.
Measured: 1 year
Number of patients who develop paracentesis induced circulatory dysfunction (PICD)
PICD will be defined as an increase in plasma renin activity (PRA) of >50% of the pre-treatment value to a level > 4ng/ml/hr on 6th day after paracentesis
Measured: 1 year
Number of patients who develop hyponatremia
Hyponatremia will be defined using serum sodium concentrations of <130meq/L.
Measured: 1 year
Change in Child-Turcotte-Pugh (CTP) score
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: 1 year
Number of patients who develop hypokalemia
Hypokalemia will be defined using serum potassium levels <3 meq/L
Measured: 1 year
Number of patients who develop hyperkalemia
hyperkalemia will be defined using serum potassium levels >6 meq/L
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2020
- Study startNov 2020 (estimated)
- Primary completionDec 2021 (estimated)
- Study completionApr 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory AscitesStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 114 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
- Investigators
- Virendra Singh, MD, DM, Principal investigator, PGIMER, Chandigarh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04621617
- Sponsor's protocol ID
- IEC-06/2020-1691
- Status last verified
- Nov 2020
- First submitted
- 27 Oct 2020
- Last updated
- 9 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Midodrine and Albumin in Patients With Refractory Ascites. A Randomised Controlled Trial.
- ClinicalTrials.gov ID
- NCT04621617
- Acronym / sponsor ID
- IEC-06/2020-1691
- Conditions
- Refractory Ascites
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 114 participants (estimated)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- Nov 2020 (estimated)
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Apr 2022 (estimated)
- First posted
- 9 Nov 2020 (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.
Refractory ascites is seen in 5-10% of patients with cirrhosis.Decompensated cirrhosis with refractory ascites has a mortality rate of around 40% in a year and a median survival of 6 months.Portal hypertension and splanchnic vasodilation are major factors in the development of ascites.The treatment of refractory ascites involves salt restriction, diuretics, large volume paracentesis (LVP), transjugular Intrahepatic Portosystemic shunt (TIPS) and Liver Transplantation (LT). Currently the only curative treatment is LT. However, LT is limited due to organ shortage and high cost.
Long-term human albumin (HA) administration in patients with uncomplicated and refractory ascites, has shown to improve survival or delay the complications of cirrhosis. Midodrine, an oral α1- adrenergic agonist has been used in refractory ascites with variable results. However, there is no study on the use of long term Midodrine and HA in patients with refractory ascites. Therefore, we plan to study the effect of long term midodrine and HA in patients with refractory ascites.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Albumin + Midodrine + SMT | Active comparator | Drug: Albumin, Drug: Midodrine, Drug: Standard medical therapy (SMT)Human albumin plus oral midodrine |
| Albumin + SMT | Active comparator | Drug: Albumin, Drug: Standard medical therapy (SMT)Human albumin plus placebo of midodrine |
| SMT | Placebo comparator | Drug: Standard medical therapy (SMT)standard medical therapy plus placebo of midodrine |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age between 18 and 80 years
- Refractory ascites in cirrhosis of any etiology
Key exclusion criteria (11 listed)
- Mixed ascites: cirrhosis plus another cause of ascites
- Gastrointestinal bleed within 7 days of enrolment.
- Presence of hepatorenal syndrome
- Hepatic encephalopathy grade 2 or higher
- Infection within 1 month preceding the study
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 |
|---|---|---|
| AlbuminHuman albumin will be administered by intravenous infusion at a dose of 1.5 gm/kg/week for 2 weeks followed by HA 40 grams every 7days | Drug | Albumin + Midodrine + SMT, Albumin + SMT |
| MidodrineOral Midodrine will be given at a dose of 7.5 mg three times in a day | Drug | Albumin + Midodrine + SMT |
| Standard medical therapy (SMT)SMT will include nutritional support, rifaximin, lactulose or lactitol, diuretics, SBP prophylaxis with norfloxacin, restriction of sodium, multivitamins, and other supportive measures as deemed necessary. LVP will be done as needed. Patients on non-selective beta blockers will continue to do so with dose modifications/withdrawal as per Baveno VI guidelines. | Drug | Albumin + Midodrine + SMT, Albumin + SMT, SMT |
Primary outcome
Number of patients with control of ascites at 1 year
Time frame: 1 year
Control of ascites will be defined as- * 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.
11 secondary outcomes
Change in estimated glomerular filtration rate (eGFR) measured by modified diet in renal disease 6 (MDRD6) formula at 3 months intervals
Time frame: 1 year
Changes in concentration of albumin at 3 months intervals
Time frame: 1 year
Change in model for end stage liver disease (MELD) score
Time frame: 1 year
Change in mean arterial pressure at 3 months interval
Time frame: 1 year
Changes in serum and 24- hour urine sodium
Time frame: 1 year
Incidence of spontaneous bacterial peritonitis (SBP) and other infections
Time frame: 1 year
Number of patients who develop paracentesis induced circulatory dysfunction (PICD)
Time frame: 1 year
Number of patients who develop hyponatremia
Time frame: 1 year
Change in Child-Turcotte-Pugh (CTP) score
Time frame: 1 year
Number of patients who develop hypokalemia
Time frame: 1 year
Number of patients who develop hyperkalemia
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2020.
- 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.
Virendra Singh, MD, DM principal investigator
PGIMER, Chandigarh
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Albumin, Midodrine and Standard medical therapy (SMT) in people with Refractory Ascites, run by Post Graduate Institute of Medical Education and Research, Chandigarh.
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 2 inclusion and 11 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 9 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 (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?
Number of patients with control of ascites at 1 year (time frame: 1 year). 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 9 Nov 2020.