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

Hala Abd EL-Tawab Ibrahim Radwan

Status and phase: Completed; Phase 2

Conditions: Hepatic Ascites

Treatments: Drug: Oral standard diuretics therapy; Drug: Etilefrine; Drug: Hypertonic saline solution

Study type: Interventional

Funder types: Other

Identifiers

NCT04785755

ascites of liver cirrhosis

Details and patient eligibility

About

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.

Full 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.

Enrollment: 90 patients

Sex: All

Ages: 25 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 4 patient groups

Group I

Active Comparator group

Description:

The control group (n=15) received oral standard diuretic 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).

Treatment:

Drug: Oral standard diuretics therapy

Group II

Experimental group

Description:

The hypertonic saline solution (HSS) group (n=25) received oral standard diuretic 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 start of the study to the end of the study) with 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.

Treatment:

Drug: Hypertonic saline solution

Drug: Oral standard diuretics therapy

Group III

Experimental group

Description:

The etilefrine group (n=25) received oral standard diuretic 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), and 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).

Treatment:

Drug: Etilefrine

Drug: Oral standard diuretics therapy

Group IV

Experimental group

Description:

The hypertonic saline solution (HSS) + Etilefrine group (n=25) received oral standard diuretic therapy (furosemide 40 mg tablet plus spironolactone 100 mg tablet with a dose increase in 40 mg100mg ratio) given once daily in the morning for 38 days (from the first day of the study to the end of the study), with 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, and 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).

Treatment:

Drug: Etilefrine

Drug: Hypertonic saline solution

Drug: Oral standard diuretics therapy