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Refractory Ascites in Children With CirrhosisNCT05084534

Efficacy and Safety of Midodrine in Refractory or Recurrent Ascites in Children With Cirrhosis.

A study testing Midodrine and Standard medical treatment in people with Refractory Ascites in Children With Cirrhosis, run by Institute of Liver and Biliary Sciences, India at 1 site in India.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

Refractory ascites is seen in 17% of cirrhotic patients with the 1year mortality rate being high, upto 20-50% [1]. The pathogenesis of cirrhotic ascites includes release of vasodilatory molecules like nitric oxide, damage associated molecular pathogens (DAMPs) and pattern associated molecular pathogens (PAMPs)… Read more about this study

Who is it for?
Ages 6 months to 18 years
What is being tested?
Midodrine and Standard medical treatment
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteIndia
Study dates
1 Nov 2021to Mar 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 6 months 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 refractory Ascites that cannot be mobilized by sodium - restricted diet (maximum upto 2mEq/kg/day- 88meq=2gm of salt) and high-dose diuretic treatment (6 mg/kg/day of spironolactone and 2 mg/kg/day of furosemide) or optimum doses of diuretics cannot be given due to development of diuretic-induced complications (Sodium <130mEq, AKI as per KDIGO, hypovolemia, hypokalemia (<3.5meq)/hyperkalemia (>5meq); new onset HE) or ascites that recurs within 4 weeks of mobilization) or recurrent ascites ( Ascites that has recurred 3 times within 12 months despite standard medical treatment) with stable renal function (age appropriate creatinine level in last 2 weeks) attending the Pediatric Hepatology Department, ILBS will be prospectively included in this study after informed consent.

Who cannot join

  • GIT bleeding in last 1 month
  • SBP in last 1 month
  • HE grade 3 or higher
  • Septic shock
  • Hepatorenal syndrome
  • Presence of PVT
  • Renal or cardiovascular disease or arterial hypertension
  • Presence of HCC

Trial locations and contacts

1 site in 1 country.

India1 site
  • ILBS

    New Delhi, 110070

Other trials in India

About this study

Official title: Efficacy and Safety of Midodrine in Refractory or Recurrent Ascites in Children With Cirrhosis - A Randomized Controlled Trial

Refractory ascites is seen in 17% of cirrhotic patients with the 1year mortality rate being high, upto 20-50% [1]. The pathogenesis of cirrhotic ascites 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 causing sodium and water retention. The standard medical therapy for the treatment of ascites includes sodium restriction to 2mEq/kg/day with diuretics (Spirinolactone 3-6mg/kg/day and furosemide 0.5-2 mg/kg/day) and therapeutic paracentesis (>50ml/kg/day) with albumin replacement at 8g/L of ascitic fluid tapped. Refractory ascites is defined as ascites that cannot be mobilized by sodium - restricted diet (maximum upto 2mEq/kg/day- 88meq=2gm of salt) and high-dose diuretic treatment (6 mg/kg/day of spironolactone and 2 mg/kg/day of furosemide) or optimum doses of diuretics cannot be given due to development of diuretic-induced complications (Sodium <130mEq, AKI as per KDIGO, hypovolemia, hypo (<3.5meq)/hyperkalemia (>5meq); new onset HE) and recurrent ascites as ascites that has recurred within a 12 weeks period despite standard treatment. All the children and adolescents upto 18 years of age with refractory or recurrent ascites will be included in the study and randomized into 2 groups. One group will receive only standard medical therapy and other group will receive midodrine and standard medical therapy for 12 weeks. Mean arterial pressure will be monitored at every OPD visit. At the end of 12 weeks, plasma renin activity, number of therapeutic paracentesis done, change in serum sodium, estimated glomerular filtration rate and complications will be assessed.

If there is complete resolution of ascites, liver transplantation or death before 12 weeks, midodrine will be stopped.

Read the detailed description

Aim: To determine the efficacy of midodrine in combination with standard medical therapy in reduction of refractory or recurrent ascites in children with cirrhosis

Primary objective:

  • To compare the proportion of patients who will achieve partial or complete control of ascites at 12 weeks after therapy between the two groups

Secondary Objectives:

  • Comparison of total number of therapeutic paracentesis (>50ml/kg) procedures between the groups by the end of 12 weeks
  • Frequency of complete response (elimination of ascites) by 12 weeks
  • Time taken to achieve complete response
  • Frequency of partial response (persistent ascites not requiring therapeutic paracentesis) by 12 weeks
  • To compare change in plasma renin activity from baseline to 12 weeks
  • Change in serum sodium from baseline to 4 weeks and 12 weeks
  • Change in eGFR from baseline to 4 weeks
  • Change in MAP at 1 week, 4 weeks and 12 weeks from baseline
  • Comparison of proportion of patients with transplant free survival at 12 weeks between the 2 groups
  • Frequency of worsening HE by 12 weeks
  • Frequency of development of HRS by 12 weeks
  • Proportion of patients developing hypertension at 12 weeks
  • Frequency of development of adverse effects by 12 weeks

Methodology:

  • Study population : Children and Adolescents with cirrhosis and refractory or recurrent ascites with stable renal function (age appropriate creatinine level in last 2 weeks) attending the Pediatric Hepatology Department
  • Study design:

Open label RCT (computer based randomization - block randomization with block size of 4)

  • Study period:12 weeks for each patient; The study will be conducted between September 2021 and December 2022
  • Sample size: Pilot study - 10 patients in each group
  • Intervention:
  • Standard Medical Treatment will be continued in all, which includes,
  • To continue restriction of sodium to < 2meq/kg/day
  • To continue maximum tolerable dose of diuretics
  • Repeat LVP with infusion of albumin (8 g/L) performed for tense, symptomatic ascites
  • Albumin infusion for serum albumin <2.5g/dl - dose 1g/kg/day (maximum 20g/day)
  • Midodrine starting at 0.25mg/kg/day in divided doses, increased to 0.5mg/kg/day after 7 days if MAP does not increase by >10% (maximum dose - 15mg/day)
  • Midodrine dosage will be decreased by 25% in case of arterial hypertension (>95th centile BP for the age)

Monitoring and assessment :

  • Abdominal girth, Blood pressure (MAP) , HE - every visit (1-2 weekly)
  • Haemogram, INR, Liver function test, Kidney function test- every 2 weekly
  • Bedside Ultrasound - every visit (1-2 weekly)
  • Plasma renin activity at baseline and 12 weeks
  • Need for therapeutic paracentesis (tense ascites causing respiratory embarrassment) at every visit (1-2 weekly)

Adverse effects: Hypertension , Bradycardia, Piloerection, Pruritus, Dysuria

Stopping rule of the study:

  • Complete resolution of ascites or 12 weeks of midodrine therapy whichever is earlier
  • Liver transplantation
  • Death without transplantation
  • TIPSS
Being tested
Midodrine, Standard medical treatment

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MidodrineDrug

    Midodrine starting at 0.25mg/kg/day in divided doses, increased to 0.5mg/kg/day after 7 days if MAP does not increase by >10% (maximum dose - 15mg/day)

    • Midodrine dosage will be decreased by 25% in case of arterial hypertension (>95th centile BP for the age)
  • Standard medical treatmentOther

    Standard Medical Treatment will be continued in all, which includes,

    • To continue restriction of sodium to < 2meq/kg/day
    • To continue maximum tolerable dose of diuretics
    • Repeat LVP with infusion of albumin (8 g/L) performed for tense, symptomatic ascites
    • Albumin infusion for serum albumin <2.5g/dl - dose 1g/kg/day (maximum 20g/day)
Study groups in NCT05084534
Study groupRoleWhat they receive
Midodrine hydrochloride plus standard medical treatmentExperimental* Standard Medical Treatment will be continued in all, which includes, * To continue restriction of sodium to < 2meq/kg/day * To continue maximum tolerable dose of diuretics * Repeat LVP with infusion of albumin (8 g/L) performed for tense, symptomatic ascites * Albumin infusion for serum albumin <2.5g/dl - dose 1g/kg/day (maximum 20g/day) * Midodrine starting at 0.25mg/kg/day in divided doses, increased to 0.5mg/kg/day after 7 days if MAP does not increase by >10% (maximum dose - 15mg/day) * Midodrine dosage will be decreased by 25% in case of arterial hypertension (>95th centile BP for the age)
Receives: Drug: Midodrine; Other: Standard medical treatment
Standard medical treatmentOther* Standard Medical Treatment will be continued in all, which includes, * To continue restriction of sodium to < 2meq/kg/day * To continue maximum tolerable dose of diuretics * Repeat LVP with infusion of albumin (8 g/L) performed for tense, symptomatic ascites * Albumin infusion for serum albumin <2.5g/dl - dose 1g/kg/day (maximum 20g/day)
Receives: Other: Standard medical treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. • To compare the proportion of patients who will achieve partial or complete control of ascites at 12 weeks after therapy between the two groups

    Measured: 12 weeks

Secondary outcomes (13)
  1. • Comparison of total number of therapeutic paracentesis (>50ml/kg) procedures between the groups by the end of 12 weeks

    Measured: 12 weeks

  2. • Frequency of complete response (elimination of ascites) by 12 weeks

    Measured: 12 weeks

  3. • Time taken to achieve complete response

    Measured: 12 weeks

  4. • Frequency of partial response (persistent ascites not requiring therapeutic paracentesis) by 12 weeks

    Measured: 12 weeks

  5. • To compare change in plasma renin activity from baseline to 12 weeks

    Measured: 12 weeks

  6. • Change in serum sodium from baseline to 4 weeks and 12 weeks

    Measured: 12 weeks

  7. • Change in eGFR from baseline to 4 weeks

    Measured: 4 weeks

  8. • Change in MAP at 1 week, 4 weeks and 12 weeks from baseline

    Measured: 12 weeks

  9. • Comparison of proportion of patients with transplant free survival at 12 weeks between the 2 groups

    Measured: 12 weeks

  10. • Frequency of worsening HE by 12 weeks

    Measured: 12 weeks

  11. • Frequency of development of HRS by 12 weeks

    Measured: 12 weeks

  12. • Proportion of patients developing hypertension at 12 weeks

    Measured: 12 weeks

  13. • Frequency of development of adverse effects by 12 weeks

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 2021
  2. Study start1 Nov 2021
  3. Primary completionFeb 2023 (estimated)
  4. Study completionMar 2023 (estimated)

Why it stopped: No cases of refractory ascites presented to hospital in one year

Resources

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05084534
Sponsor's protocol ID
ILBS-Cirrhosis-47
Status last verified
Oct 2021
First submitted
18 Oct 2021
Last updated
7 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A study testing Midodrine and Standard medical treatment in people with Refractory Ascites in Children With Cirrhosis, 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 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: withdrawn, as of the sponsor's last update on 7 May 2024. 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 was withdrawn before enrolling participants, so there are no results.

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?

• To compare the proportion of patients who will achieve partial or complete control of ascites at 12 weeks after therapy between the two groups (time frame: 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 7 May 2024.

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