Cirrhosis, LiverNCT05287100
To Assess the Efficacy of Midodrine in Prevention of Cirrhosis Related Complications in Children Awaiting Liver Transplantation.
A study testing Midodrine Oral Tablet and Standard Medical Treatment in people with Cirrhosis, Liver, run by Institute of Liver and Biliary Sciences, India at 1 site in India.
Trial summary
Children with cirrhosis awaiting transplantation are more proned to develop various complications. The pathogenesis of cirrhotic complications (ascites, hyponatremia, acute kidney injury) includes release of vasodilatory molecules like nitric oxide, damage associated molecular pathogens (DAMPs) and pattern associated… Read more about this study
- Who is it for?
- Ages 10 days to 18 years
- Conditions the study is for
- Cirrhosis, Liver
- What is being tested?
- Midodrine Oral Tablet and Standard Medical Treatment
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteIndia
- Study dates
- 1 Jan 2022to 30 May 2023
- Phase
- Interventional
- 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 10 days to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Children and Adolescents of age group upto 18 years with cirrhosis and PELD/ MELDNa score more than 14, on waitlist for liver transplantation following up in the Pediatric Hepatology Department, ILBS will be prospectively included in this study after informed consent
Who cannot join
- Presence of Portal vein thrombosis Renal or cardiovascular disease or arterial hypertension Presence of HCC
Trial locations and contacts
1 site in 1 country.
About this study
Official title: To Assess the Efficacy of Midodrine in Prevention of Cirrhosis Related Complications in Children Awaiting Liver Transplantation
Children with cirrhosis awaiting transplantation are more proned to develop various complications. The pathogenesis of cirrhotic complications (ascites, hyponatremia, acute kidney injury) includes release of vasodilatory molecules like nitric oxide, damage associated molecular pathogens (DAMPs) and pattern associated molecular pathogens (PAMPs) secondary to bacterial translocation, which causes splanchnic bed vasodilation resulting in activation of renin-angiotensin and aldosterone axis(RAAS) causing sodium and water retention and renal vasoconstriction [1].
The development of complications in these children may result in death or may preclude them from reaching upto liver transplantation [2].
Read more
Midodrine is an α1 adrenergic receptor agonist, which increases vascular tone causing rise in the blood pressure, thereby improving renal perfusion and causes RAAS deactivation. The effects of midodrine is documented in reduction of refractory ascites, hepatorenal syndrome and hyponatremia[2-4].
One group will receive only standard medical therapy and other group will receive midodrine and standard medical therapy for 6 months. Mean arterial pressure will be monitored at every OPD visit. At the end of 12 weeks, and 24 weeks, plasma renin activity, incidence of complications related to cirrhosis like new onset ascites, increase in grade of ascites, hyponatremia, acute kidney injury and spontaneous bacterial peritonitis will be assessed. Also the transplant free survival and need for albumin transfusion will be compared between the two groups.
In case of liver transplantation or death before 6 months, midodrine will be stopped
Read the detailed description
Aim: To determine the efficacy of midodrine in preventing development of complications in children with cirrhosis awaiting liver transplantation
Primary Objective:
- To compare incidence of complications (Acute kidney injury, New onset ascites or increase in grade of ascites, Spontaneous bacterial peritonitis, Hyponatremia, Hepatic encephalopathy) of cirrhosis in patients receiving midodrine (at a dose of 0.25 - 0.5mg/kg/day) and standard medical therapy versus standard medical therapy alone for 6 months
Secondary Objectives:
- Frequency of development of new onset ascites or increase in grade of ascites by 6 months
- Change in serum sodium from baseline to 6 months
- Change in Mean arterial pressure (MAP) at 1 week and then 2 weekly till the end of the study
- Plasma renin activity at baseline, at 12 weeks and 24 weeks
- Frequency of development of SBP over 6 months
- Change in eGFR from baseline to 6 months
- Frequency of developing AKI by 6 months
- Frequency of development of Hepatic encephalopathy by 6 months
- Proportion of patients developing hypertension at 6 months
- Frequency of development of drug related adverse effects by 6 months
- Requirement of albumin infusion in 2 groups
- Transplant free survival
Methodology:
- Study population :Children and Adolescents of age group upto 18 years with cirrhosis and PELD/ MELDNa score more than 14, on waitlist for liver transplantation following up in the Pediatric Hepatology Department
- Study design: Open label RCT (computer based randomization - block randomization with block size of 4)
- Study period: 6 months weeks for each patient; The study will be conducted between January 2022 and July 2023
- Sample size:
- Pilot study - 10 patients in each group
- Conditions
- Cirrhosis, Liver
- Being tested
- Midodrine Oral Tablet, Standard Medical Treatment
- Medical subject headings
- Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Midodrine Oral TabletDrug
Midodrine starting at 0.25mg/kg/day in 2-3 divided doses, increased to 0.5mg/kg/day after 7 days if MAP does not increase by >10% ; Midodrine dosage will be decreased by 25% in case of arterial hypertension (>95th centile BP for the age). Also Standard medical therapy as per departmental protocol will be continued
Standard Medical TreatmentOther
Albumin infusion 1g/kg/day - maximum 20gm/day and repeat till serum albumin reaches 2.8g/dl If serum albumin is < 2.8g/dl SBP - Day 1 and Day 3
For Ascites :
Restriction of sodium to < 2meq/kg/day A combination of a distal-acting diuretic (spironolactone, 3-6 mg/ kg/day) and loop-acting diuretic (furosemide,0.5- 2 mg/kg per day) was given with dose escalation by one step at a time if there is no decrease in weight (by ≥ 0.5 %/day) after 5-7 days Therapeutic paracentesis (>50ml/kg) with infusion of albumin (8 g/L) performed for tense, symptomatic ascites
For Spontaneous Bacterial Peritonitis :
IV antibiotics for 7 days Albumin Infusion on Day 1 and Day 3
| Study group | Role | What they receive |
|---|---|---|
| Midodrine | Experimental | Midodrine starting at 0.25mg/kg/day in 2-3 divided doses, increased to 0.5mg/kg/day after 7 days if MAP does not increase by >10% ; Midodrine dosage will be decreased by 25% in case of arterial hypertension (>95th centile BP for the age). Also Standard medical therapy as per departmental protocol will be continued Receives: Drug: Midodrine Oral Tablet; Other: Standard Medical Treatment |
| Standard medical therapy | Active comparator | Standard medical therapy as per departmental protocol Receives: Other: Standard Medical Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complications between the two groups
- To compare incidence of complications (Acute kidney injury, New onset ascites or increase in grade of ascites, Spontaneous bacterial peritonitis, Hyponatremia, Hepatic encephalopathy) of cirrhosis in patients receiving midodrine (at a dose of 0.25 - 0.5mg/kg/day) and standard medical therapy versus standard medical therapy alone for 6 months
Measured: 6 months
Secondary outcomes (12)
• Frequency of development of new onset ascites or increase in grade of ascites by 6 months
Measured: 6 months
Change in serum sodium from baseline to 6 months
Measured: 6 months
Change in Mean arterial pressure (MAP) at 1 week and then 2 weekly till the end of the study
Measured: 6 months
Plasma renin activity at baseline, at 12 weeks and 24 weeks
Measured: 6 months
Frequency of development of SBP over 6 months
Measured: 6 months
Change in eGFR from baseline to 6 months
Measured: 6 months
Frequency of developing AKI by 6 months
Measured: 6 months
Frequency of development of Hepatic encephalopathy by 6 months
Measured: 6 months
Proportion of patients developing hypertension at 6 months
Measured: 6 months
Frequency of development of drug related adverse effects by 6 months
Measured: 6 months
Requirement of albumin infusion in 2 groups
Measured: 6 months
Transplant free survival
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 posted18 Mar 2022
- Study start1 Jan 2022
- Primary completion30 May 2023
- Study completion30 May 2023
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 Cirrhosis, LiverStudies of the same condition, open and under way.
- More trials run by Institute of Liver and Biliary Sciences, IndiaThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Liver and Biliary Sciences, India
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Prof. Seema Alam, MD, Study director, ILBS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05287100
- Sponsor's protocol ID
- ILBS-Cirrhosis-49
- Status last verified
- Oct 2023
- First submitted
- 11 Mar 2022
- Last updated
- 10 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ashritha A, Lal BB, Khanna R, Sood V, Sood AK, Alam S. Midodrine reduces new-onset acute kidney injury and hyponatremia in children with cirrhosis and ascites awaiting liver transplantation: Results from an open-label RCT. J Pediatr Gastroenterol Nutr. 2024 Feb;78(2):350-359. doi: 10.1002/jpn3.12077. Epub 2023 Dec 11.
PubMed 38374552
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- To Assess the Efficacy of Midodrine in Prevention of Cirrhosis Related Complications in Children Awaiting Liver Transplantation
- ClinicalTrials.gov ID
- NCT05287100
- Acronym / sponsor ID
- ILBS-Cirrhosis-49
- Conditions
- Cirrhosis, Liver
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Institute of Liver and Biliary Sciences, IndiaUniversity, hospital or other
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 30 May 2023 (actual)
- Study completion
- 30 May 2023 (actual)
- First posted
- 18 Mar 2022 (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.
Children with cirrhosis awaiting transplantation are more proned to develop various complications. The pathogenesis of cirrhotic complications (ascites, hyponatremia, acute kidney injury) includes release of vasodilatory molecules like nitric oxide, damage associated molecular pathogens (DAMPs) and pattern associated molecular pathogens (PAMPs) secondary to bacterial translocation, which causes splanchnic bed vasodilation resulting in activation of renin-angiotensin and aldosterone axis(RAAS) causing sodium and water retention and renal vasoconstriction [1].
The development of complications in these children may result in death or may preclude them from reaching upto liver transplantation [2].
Midodrine is an α1 adrenergic receptor agonist, which increases vascular tone causing rise in the blood pressure, thereby improving renal perfusion and causes RAAS deactivation. The effects of midodrine is documented in reduction of refractory ascites, hepatorenal syndrome and hyponatremia[2-4].
One group will receive only standard medical therapy and other group will receive midodrine and standard medical therapy for 6 months. Mean arterial pressure will be monitored at every OPD visit. At the end of 12 weeks, and 24 weeks, plasma renin activity, incidence of complications related to cirrhosis like new onset ascites, increase in grade of ascites, hyponatremia, acute kidney injury and spontaneous bacterial peritonitis will be assessed. Also the transplant free survival and need for albumin transfusion will be compared between the two groups.
In case of liver transplantation or death before 6 months, midodrine will be stopped
Detailed description
Aim: To determine the efficacy of midodrine in preventing development of complications in children with cirrhosis awaiting liver transplantation
Primary Objective:
- To compare incidence of complications (Acute kidney injury, New onset ascites or increase in grade of ascites, Spontaneous bacterial peritonitis, Hyponatremia, Hepatic encephalopathy) of cirrhosis in patients receiving midodrine (at a dose of 0.25 - 0.5mg/kg/day) and standard medical therapy versus standard medical therapy alone for 6 months
Secondary Objectives:
- Frequency of development of new onset ascites or increase in grade of ascites by 6 months
- Change in serum sodium from baseline to 6 months
- Change in Mean arterial pressure (MAP) at 1 week and then 2 weekly till the end of the study
- Plasma renin activity at baseline, at 12 weeks and 24 weeks
- Frequency of development of SBP over 6 months
- Change in eGFR from baseline to 6 months
- Frequency of developing AKI by 6 months
- Frequency of development of Hepatic encephalopathy by 6 months
- Proportion of patients developing hypertension at 6 months
- Frequency of development of drug related adverse effects by 6 months
- Requirement of albumin infusion in 2 groups
- Transplant free survival
Methodology:
- Study population :Children and Adolescents of age group upto 18 years with cirrhosis and PELD/ MELDNa score more than 14, on waitlist for liver transplantation following up in the Pediatric Hepatology Department
- Study design: Open label RCT (computer based randomization - block randomization with block size of 4)
- Study period: 6 months weeks for each patient; The study will be conducted between January 2022 and July 2023
- Sample size:
- Pilot study - 10 patients in each group
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Midodrine | Experimental | Drug: Midodrine Oral Tablet, Other: Standard Medical TreatmentMidodrine starting at 0.25mg/kg/day in 2-3 divided doses, increased to 0.5mg/kg/day after 7 days if MAP does not increase by >10% ; Midodrine dosage will be decreased by 25% in case of arterial hypertension (>95th centile BP for the age). Also Standard medical therapy as per departmental protocol will be continued |
| Standard medical therapy | Active comparator | Other: Standard Medical TreatmentStandard medical therapy as per departmental protocol |
Who may qualify
- Ages
- 10 days to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- Children and Adolescents of age group upto 18 years with cirrhosis and PELD/ MELDNa score more than 14, on waitlist for liver transplantation following up in the Pediatric Hepatology Department, ILBS will be prospectively included in this study after informed consent
Key exclusion criteria (1 listed)
- Presence of Portal vein thrombosis Renal or cardiovascular disease or arterial hypertension Presence of HCC
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 |
|---|---|---|
| Midodrine Oral TabletMidodrine starting at 0.25mg/kg/day in 2-3 divided doses, increased to 0.5mg/kg/day after 7 days if MAP does not increase by >10% ; Midodrine dosage will be decreased by 25% in case of arterial hypertension (>95th centile BP for the age). Also Standard medical therapy as per departmental protocol will be continued | Drug | Midodrine |
| Standard Medical TreatmentAlbumin infusion 1g/kg/day - maximum 20gm/day and repeat till serum albumin reaches 2.8g/dl If serum albumin is < 2.8g/dl SBP - Day 1 and Day 3 For Ascites : Restriction of sodium to < 2meq/kg/day A combination of a distal-acting diuretic (spironolactone, 3-6 mg/ kg/day) and loop-acting diuretic (furosemide,0.5- 2 mg/kg per day) was given with dose escalation by one step at a time if there is no decrease in weight (by ≥ 0.5 %/day) after 5-7 days Therapeutic paracentesis (>50ml/kg) with infusion of albumin (8 g/L) performed for tense, symptomatic ascites For Spontaneous Bacterial Peritonitis : IV antibiotics for 7 days Albumin Infusion on Day 1 and Day 3 | Other | Midodrine, Standard medical therapy |
Primary outcome
Complications between the two groups
Time frame: 6 months
• To compare incidence of complications (Acute kidney injury, New onset ascites or increase in grade of ascites, Spontaneous bacterial peritonitis, Hyponatremia, Hepatic encephalopathy) of cirrhosis in patients receiving midodrine (at a dose of 0.25 - 0.5mg/kg/day) and standard medical therapy versus standard medical therapy alone for 6 months
12 secondary outcomes
• Frequency of development of new onset ascites or increase in grade of ascites by 6 months
Time frame: 6 months
Change in serum sodium from baseline to 6 months
Time frame: 6 months
Change in Mean arterial pressure (MAP) at 1 week and then 2 weekly till the end of the study
Time frame: 6 months
Plasma renin activity at baseline, at 12 weeks and 24 weeks
Time frame: 6 months
Frequency of development of SBP over 6 months
Time frame: 6 months
Change in eGFR from baseline to 6 months
Time frame: 6 months
Frequency of developing AKI by 6 months
Time frame: 6 months
Frequency of development of Hepatic encephalopathy by 6 months
Time frame: 6 months
Proportion of patients developing hypertension at 6 months
Time frame: 6 months
Frequency of development of drug related adverse effects by 6 months
Time frame: 6 months
Requirement of albumin infusion in 2 groups
Time frame: 6 months
Transplant free survival
Time frame: 6 months
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 10 Oct 2023.
- Derived from this study: PubMed 38374552Ashritha A, Lal BB, Khanna R, Sood V, Sood AK, Alam S. Midodrine reduces new-onset acute kidney injury and hyponatremia in children with cirrhosis and ascites awaiting liver transplantation: Results from an open-label RCT. J Pediatr Gastroenterol Nutr. 2024 Feb;78(2):350-359. doi: 10.1002/jpn3.12077. Epub 2023 Dec 11.
- 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.
Prof. Seema Alam, MD study director
ILBS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Midodrine Oral Tablet and Standard Medical Treatment in people with Cirrhosis, Liver, run by Institute of Liver and Biliary Sciences, India 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 1 inclusion and 1 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 10 Oct 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 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Complications between the two groups (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 NCT05287100, 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 10 Oct 2023.