Effects of Adding Hypertonic Saline Solutions and/or Etilefrine to Standard Diuretics Therapy in Hepatic Ascites
Condition: Hepatic Ascites
MeSH terms: Ascites
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Oral standard diuretics therapy; Hypertonic saline solution; Etilefrine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Oral standard diuretics therapy (furosemide 40 mg tablet plus spironolactone 100 mg tablet with a dose increase in 40 mg:100 mg ratio) given once daily in the morning for 38 days (from the first day of the study to the end of the study).; Hypertonic saline solution (150ml, 1.4% - 4.6%) infused slowly over one hour peripherally once daily from the first day of the study for eight days.; Etilefrine 5 mg tablet given by mouth three times daily for 38 days (from the first day of the study to the end of the study).
Other intervention name(s): Furosemide (lasix®), Spironolactone (Aldactone®); prepared from sodium chloride 0.9% intravenous solution and sodium chloride 3% intravenous solution (, Egypt Otsuka Pharmaceutical Co.).; (Vascon®)
Intervention MeSH terms: Etilefrine; Furosemide; Spironolactone; Pharmaceutical Solutions; Diuretics
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Ascites, Hypertonic saline, Etilefrine, Aldosterone, Leptin.