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NCT ID: NCT05084534 Withdrawn - Clinical trials for Refractory Ascites in Children With Cirrhosis

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

Start date: November 1, 2021
Phase: N/A
Study type: Interventional

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.

NCT ID: NCT05057572 Recruiting - Liver Cirrhosis Clinical Trials

Efficacy and Safety of Carvedilol in Cirrhosis Patients With Uncomplicated Ascites Without High Risk Esophageal Varices

Start date: October 1, 2021
Phase: N/A
Study type: Interventional

The cumulative risk of refractory ascites is in the order of 20% within five years of the development of ascites. An elevated sinusoidal pressure is essential for the development of ascites, as fluid accumulation does not develop at portal pressure gradient below 8 mm Hg, and rising corrected sinusoidal pressure correlates with decreased 24-hour urinary excretion of sodium.More recently, it has been hypothesised that bacterial translocation associated with portal hypertension in cirrhosis and related pathogen-associated, molecular pattern activated innate immune responses lead to systemic inflammation.This is associated with vasodilatation as well as release of proinflammatory cytokines, reactive oxygen and nitrogen species, contributing to organ dysfunction.This activates sympathetic nervous system stimulating reabsorption of sodium in proximal,distal tubules, loop of Henle and collecting duct as well as the renin-angiotensin-aldosterone system, leading to sodium absorption from distal tubule and collecting duct.[5]Renal sodium retention and eventual free water clearance due to non-osmoticrelease of arginine-vasopressin and its action on V2 receptor in the collectingduct underlie the fluid retention associated with oedema and ascites in cirrhosis.The lowering of portal pressure using non selective beta blocker has also been shown to reduce the development of ascites, refractory ascites and hepatorenal syndrome.Furthermore, the effect of non slective beta blocker on intestinal permeability, bacterial translocation and inflammatory response has been proposed to mitigate the risk of developing spontaneous bacterial peritonitis.

NCT ID: NCT05056220 Recruiting - Clinical trials for Decompensated Cirrhosis and Ascites

Personalized Long-term Human Albumin Treatment in Patients With Decompensated Cirrhosis and Ascites

Start date: February 26, 2024
Phase: Phase 3
Study type: Interventional

The goal of this clinical biomarker validation trial is to test the effect of a predictive biomarker panel to human albumin infusions in patients with liver cirrhosis and ascites. The main questions it aims to answer are: - If the predictive biomarker panel can identify patients who are likely to benefit from regular human albumin infusions - If the predictive biomarker panel can lower the number-needed-to-treat of regular human albumin infusions in patients with liver cirrhosis and ascites The predictive biomarker panel will stratify patients into either a high- or low-expected effect of human albumin infusions. Hereafter are participants randomized into treatment arms. Participants in the active treatment arm will receive regular human albumin infusions during a course of 6 months. Infusions will occur every 10th day for the duration of the study. Researchers will compare 20% human albumin infusions with regular 0.9% sodium chloride to identify the effects on the number of liver-related events.

NCT ID: NCT05025878 Recruiting - Ovarian Cancer Clinical Trials

13C-Glucose Tracing of Tumour and T Cells in the Ascites of Ovarian Cancer Patients.

iMETABO
Start date: October 20, 2021
Phase:
Study type: Observational

The objective of the study is to investigate the metabolism of cells in the ascites tumour microenvironment of ovarian cancer patients. This observational study involves intravenous infusion of [U-13C]glucose into patients during standard paracentesis.

NCT ID: NCT05014594 Recruiting - Cirrhosis Clinical Trials

Sodium-glucose Linked Transporter 2 (SGLT-2) Inhibitors in Recurrent Ascites: a Pilot RCT

Start date: September 3, 2021
Phase: Phase 2
Study type: Interventional

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.

NCT ID: NCT05013502 Completed - Liver Cirrhosis Clinical Trials

Empagliflozin in Diuretic Refractory Ascites

DRAin-Em 01
Start date: November 15, 2021
Phase: Phase 1
Study type: Interventional

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.

NCT ID: NCT04985357 Not yet recruiting - Clinical trials for Carcinoma, Non-Small-Cell Lung

Defining the Clinical Potential of Mass Response as a Biomarker for Patient Tumor Sensitivity to Drugs

Start date: June 2024
Phase:
Study type: Observational

The primary objective of this study, sponsored by Travera in Massachusetts, is to validate whether the mass response biomarker has potential to predict response of patients to specific therapies or therapeutic combinations using isolated tumor cells from varying cancers and biopsy formats.

NCT ID: NCT04835480 Recruiting - Cirrhotic Ascites Clinical Trials

A Phase II Study of OsrHSA in Patients With Decompensated Cirrhotic Ascites

Start date: March 22, 2021
Phase: Phase 2
Study type: Interventional

The study is designed to study the efficacy of IV OsrHSA or positive control HSA (10 g and 20 g IV everyday) for 14 days. After a screening period of up to 14 days, the eligible subjects will be randomized in a 4:1 ratio to OsrHSA and positive control HSA, respectively, in each cohort. Each enrolled subject will receive multiple assigned doses of OsrHSA. The Investigator and subjects will be blind to treatment assignment (OsrHSA or positive control HSA) in each cohort. During the study, subjects will be evaluated for efficacy, safety, tolerability, and immunogenicity. In each cohort, subjects will be stratified by baseline serum albumin level. If serum albumin reaches 35 g/L or more, the study drug or control drug administration may be terminated early. Subjects will have 3 follow-up visits in 2 weeks.

NCT ID: NCT04816240 Recruiting - Liver Cirrhosis Clinical Trials

Evaluation of Albumin and Midodrine Versus Albumin Alone in Outcome of Refractory Ascites in Patients With Decompensated Cirrhosis.

Start date: May 15, 2021
Phase: N/A
Study type: Interventional

The project is about evaluation of albumin and midodrine versus albumin alone in outcome of refractory ascites in patients with decompensated cirrhosis. Cirrhosis is a leading cause of disability and mortality worldwide. Cirrhosis occurs in 50% of patients over 10 years. Decompensated cirrhosis carries a poor prognosis because the median survival time is about 2 years and it imposes a heavy burden on health care costs mainly due to the need for repeated hospital admission. The mortality is approximately 40% at 1 year and 50% at 2 years (12.7 per 100,000 population). A lot of times the prognosis is poor and the main factors leading to it are - AKI/HRS-NAKI, Hyponatremia, Grade of ascites-Refractory ascites, Sarcopenia, low Mean arterial pressure. Post review of the literature, it is realized that there are some gap areas - - It is unknown whether combination of vasoconstrictor with albumin further decreases the need for paracentesis in patients of refractory ascites. - There are no studies till date on using combination of vasoconstrictor with albumin for refractory ascites. - There are no studies evaluating the prevalence and incidence of HRS-NAKI using the new definitions in patients with refractory ascites and impact of combining vasoconstrictor and albumin in improving renal outcomes in these patients.

NCT ID: NCT04785755 Completed - Hepatic Ascites Clinical Trials

Effects of Adding Hypertonic Saline Solutions and/or Etilefrine to Standard Diuretics Therapy in Hepatic Ascites

Start date: November 30, 2017
Phase: Phase 2
Study type: Interventional

This work aimed to evaluate and compare the impact of adding hypertonic saline solution (HSS) infusion and/or etilefrine to oral diuretics therapy on clinical outcomes, renal and systemic hemodynamics, metabolic and inflammatory pathways by estimating the changes in selected biological markers in cirrhotic patients with ascites. Also, the trial aims to assess the safety and tolerability of such treatment regimens.