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

NCT ID: NCT04785755

Last Updated: 2021-03-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-30

Study Completion Date

2020-04-30

Brief Summary

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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

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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.

Conditions

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Hepatic Ascites

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group I

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).

Group Type ACTIVE_COMPARATOR

Oral standard diuretics therapy

Intervention Type DRUG

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).

Group II

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.

Group Type EXPERIMENTAL

Oral standard diuretics therapy

Intervention Type DRUG

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

Intervention Type DRUG

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.

Group III

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).

Group Type EXPERIMENTAL

Oral standard diuretics therapy

Intervention Type DRUG

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).

Etilefrine

Intervention Type DRUG

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).

Group IV

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).

Group Type EXPERIMENTAL

Oral standard diuretics therapy

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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).

Interventions

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Oral standard diuretics therapy

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).

Intervention Type DRUG

Hypertonic saline solution

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.

Intervention Type DRUG

Etilefrine

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).

Intervention Type DRUG

Other Intervention Names

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Furosemide (lasix®), Spironolactone (Aldactone®) prepared from sodium chloride 0.9% intravenous solution and sodium chloride 3% intravenous solution (, Egypt Otsuka Pharmaceutical Co.). (Vascon®)

Eligibility Criteria

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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.
Minimum Eligible Age

25 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hala Abd EL-Tawab Ibrahim Radwan

OTHER

Sponsor Role lead

Responsible Party

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Hala Abd EL-Tawab Ibrahim Radwan

clinical pharmacy master degree, pharm D

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Gamal A Badra, professor

Role: STUDY_DIRECTOR

national liver institute / menoufiya university

Sahar El-Haggar, professor

Role: STUDY_DIRECTOR

Tanta University

hala El said, professor

Role: STUDY_DIRECTOR

national liver institute / menoufiya university

Locations

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National liver institute- menoufiya university

Shibīn al Kawm, Monufia Governorate, Egypt

Site Status

Countries

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Egypt

References

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Other Identifiers

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ascites of liver cirrhosis

Identifier Type: -

Identifier Source: org_study_id

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