Clinical trial NCT04785755: Effects of Adding Hypertonic Saline Solutions and/or Etilefrine to Standard Diuretics Therapy in Hepatic Ascites
Official title: Effects of Adding Hypertonic Saline Solutions and/or Etilefrine to Standard Diuretics Therapy in Egyptian Cirrhotic Patients With Ascites
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatic Ascites
Keywords: Ascites, Hypertonic saline, Etilefrine, Aldosterone, Leptin.
Lead sponsor: Tanta University
Sponsor class: OTHER
First posted: 2021-03-08
Enrollment: 90
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: This comparative, randomized, prospective controlled clinical trial was conducted on 90 cirrhotic patients with ascites who were admitted to the Hepatology Department of National Liver Institute, Menoufiya University. The study was approved by the Institution Review Board (IRB) of the National Liver Institute (NLI), Menoufiya University, Egypt with NLI/IRB protocol number: 00131/2017. Informed consent was obtained from all patients who participated in the study.

Patients were randomized into four groups:

Group I: (n=15) received oral standard diuretic therapy (furosemide 40 mg plus spironolactone 100 mg with dose increase in 40 mg :100 mg ratio).

Group II: (n=25) received (150 ml,1.4% - 4.6%) of hypertonic saline solution (HSS) plus standard diuretics therapy.

Group III: (n=25) received etilefrine 5 mg tablets 3 times daily plus standard diuretics therapy.

Group IV: (n=25) received (150 ml, 1.4% - 4.6%) of HSS and etilefrine 5 mg tablets 3 times daily plus standard diuretics therapy.

Time frame:

Oral standard diuretics therapy administered for 38 days. Etilefrine tablets administered for 38 days. Infusion of HSS administered for eight days. Diuretics dosage reassessed according to blood pressure, diuresis, serum sodium, and serum potassium levels.

All blood and urine samples were collected and measured as follows:

1. At baseline before initiation of any treatment (first measurement)
2. Eight days after treatment with studied medications (second measurement).
3. One month after the second measurement (third measurement).

Samples collection:

Venous blood samples were drawn from enrolled patients in the morning before treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement). Blood samples were centrifuged and the resulting supernatant was frozen at -80 C until all samples were collected. 24-hr urine was collected in the morning from 7 am to 7 am of the next day before initiation of treatment, after eight days of treatment, and after a month from the second measurement to assess diuresis and urinary creatinine, urinary Na, and urinary K, also hepatic and renal functions, complete blood count, serum levels of c-reactive protein, interleukin-6, aldosterone, and leptin were measured at baseline, after eight days and, after a month from the second measurement.

Eligibility criteria: Inclusion Criteria:

* All cirrhotic patients with ascites grade I- III.
* Patients ages from 25 -65 years.

Exclusion Criteria:

* Non-cirrhotic ascites.
* Congestive heart failure.
* Acute renal failure.
* Hepatocellular carcinoma.
* All Cancer types.
* Arterial hypertension.
* Acute infection.

Primary outcomes:
measure: Evaluate and compare the impact of adding hypertonic saline solution (HSS) infusion and/or etilefrine to oral standard diuretics therapy on the inflammatory pathway in cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
measure: Evaluate and compare the impact of adding HSS infusion and/or etilefrine to oral standard diuretics therapy on the serum C-reactive protein in cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
measure: Evaluate and compare the effect of adding HSS infusion and/or etilefrine to the standard oral standard diuretics therapy on the metabolic pathway in cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
measure: Evaluate and compare the impact of adding HSS solution infusion and/or etilefrine to oral standard diuretics therapy on the renal hemodynamics in cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
measure: Evaluate and compare the impact of adding HSS infusion and/or etilefrine to oral diuretics therapy on the diuresis of cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
measure: Evaluate and compare the effect of adding HSS infusion and/or etilefrine to oral diuretics therapy on the systemic hemodynamic of cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
measure: Evaluate the effect of adding HSS infusion and/or etilefrine to oral diuretics therapy on serum sodium (Na) concentration in cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
measure: Evaluate the effect of adding HSS infusion and/or etilefrine to oral diuretics therapy on serum creatinine concentration in cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
Secondary outcomes:
measure: Evaluate the effect of adding HSS infusion and/or etilefrine to oral diuretics therapy on prothrombin concentration in cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
measure: Evaluate and compare the effect of adding HSS infusion and/or etilefrine to oral diuretics therapy on the model of end-stage liver disease (MELD score)in cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
measure: Evaluate and compare the effect of adding HSS infusion and/or etilefrine to the standard oral diuretics therapy on the model of end-stage liver disease depending on sodium (MELD score-Na)in cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
measure: Evaluate and compare the effect of adding HSS infusion and/or etilefrine to oral diuretics therapy on Child-Pugh score in cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
measure: Evaluate and compare the effect of adding HSS infusion and/or etilefrine to the standard oral diuretics therapy on the bodyweight in cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
measure: Evaluate and compare the effect of adding HSS infusion and/or etilefrine to the standard oral diuretics therapy on urinary sodium excretion in cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
measure: Evaluate and compare the effect of adding HSS infusion and/or etilefrine to the standard oral diuretics therapy on urinary creatinine excretion in cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
measure: Evaluate and compare the effect of adding HSS infusion and/or etilefrine to the standard oral diuretics therapy on serum alanine aminotransferase enzyme (ALT) in cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
measure: Evaluate and compare the effect of adding HSS infusion and/or etilefrine to the standard oral diuretics therapy on serum albumin in cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
measure: Evaluate and compare the effect of adding HSS infusion and/or etilefrine to the standard oral diuretics therapy on serum total bilirubin in cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
measure: Evaluate and compare the effect of adding HSS infusion and/or etilefrine to the standard oral diuretics therapy on serum blood urea nitrogen (BUN) in cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
measure: Evaluate and compare the effect of adding HSS infusion and/or etilefrine to the standard oral diuretics therapy on hemoglobin concentration in cirrhotic patients with ascites.
timeFrame: 38 days (from the first day of the study to the end of the study)
Other outcomes:
measure: Safety of adding HSS infusion and/or etilefrine to the standard oral diuretics therapy in cirrhotic patients with ascites.
timeFrame: 38 days (from the start of the study to the end of the study).
measure: Tolerability of adding HSS infusion and/or etilefrine to the standard oral diuretics therapy in cirrhotic patients with ascites.
timeFrame: 38 days (from the start of the study to the end of the study).
Locations:
city: Shibīn Al Kawm
country: Egypt
facility: National liver institute- menoufiya university
state: Menoufiya
Study officials:
affiliation: national liver institute / menoufiya university
name: Gamal A Badra, professor
role: STUDY_DIRECTOR
affiliation: Tanta University
name: Sahar El-Haggar, professor
role: STUDY_DIRECTOR
affiliation: national liver institute / menoufiya university
name: hala El said, professor
role: STUDY_DIRECTOR
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