Hepatic AscitesPhase 2NCT04785755

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

A Phase 2 study testing Oral standard diuretics therapy, Hypertonic saline solution and Etilefrine in people with Hepatic Ascites, run by Hala Abd EL-Tawab Ibrahim Radwan at 1 site in Egypt.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 25 to 65 years
Conditions the study is for: Hepatic Ascites
What is being tested?: Oral standard diuretics therapy, Hypertonic saline solution and Etilefrine
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 90 participants
Where: 1 siteEgypt
Study dates: 30 Nov 2017to 30 Apr 2020
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 25 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Egypt1 site

National liver institute- menoufiya university
Shibīn al Kawm, Monufia Governorate, 32511

Other trials in Egypt

About this study

Official title: Effects of Adding Hypertonic Saline Solutions and/or Etilefrine to Standard Diuretics Therapy in Egyptian Cirrhotic Patients With Ascites

Read the 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:

At baseline before initiation of any treatment (first measurement)
Eight days after treatment with studied medications (second measurement).
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: Hepatic Ascites
Being tested: Oral standard diuretics therapy, Hypertonic saline solution, Etilefrine
Keywords: Ascites, Hypertonic saline, Etilefrine, Aldosterone, Leptin.
Medical subject headings: Ascites

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Oral standard diuretics therapyDrug
Also called Furosemide (lasix®), Spironolactone (Aldactone®)
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 solutionDrug
Also called prepared from sodium chloride 0.9% intravenous solution and sodium chloride 3% intravenous solution (, Egypt Otsuka Pharmaceutical Co.).
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.
EtilefrineDrug
Also called (Vascon®)
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).

Study groups in NCT04785755
Study group	Role	What they receive
Group I	Active comparator	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). Receives: Drug: Oral standard diuretics therapy
Group II	Experimental	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. Receives: Drug: Oral standard diuretics therapy; Drug: Hypertonic saline solution
Group III	Experimental	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). Receives: Drug: Oral standard diuretics therapy; Drug: Etilefrine
Group IV	Experimental	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). Receives: Drug: Oral standard diuretics therapy; Drug: Hypertonic saline solution; Drug: Etilefrine

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
By measuring the final change in serum interleukin-6 (pg/ml) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). All blood samples were collected for measuring from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
Measured: 38 days (from the first day of the study to the end of the study)
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.
By measuring the final change in serum C-reactive protein (mg/L) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). All blood samples were collected for measuring from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
Measured: 38 days (from the first day of the study to the end of the study)
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.
By measuring the final change in serum leptin (pg/ml) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). All blood samples were collected for measuring from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
Measured: 38 days (from the first day of the study to the end of the study)
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.
By measuring the final change in plasma aldosterone (pg/ml) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). All blood samples were collected for measuring from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
Measured: 38 days (from the first day of the study to the end of the study)
Evaluate and compare the impact of adding HSS infusion and/or etilefrine to oral diuretics therapy on the diuresis of cirrhotic patients with ascites.
By measuring the final change in 24-hour urine output (ml/24 hr) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). 24-hr urine was collected in the morning from 7 am to 7 am of the next day before treatment (first collection), after eight days of treatment (second collection), and after a month from the second collection for assessing diuresis.
Measured: 38 days (from the first day of the study to the end of the study)
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.
By measuring the effects of the treatments on mean arterial pressure (MAP) in patients with ascites. Systolic blood pressure (mmHg) and diastolic blood pressure (mmHg) were measured using a sphygmomanometer to calculate MAP first on day one of the treatments (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement). Final changes in MAP (mmHg) were calculated from the first day of the study to the end of the study (study duration 38 days)
Measured: 38 days (from the first day of the study to the end of the study)
Evaluate the effect of adding HSS infusion and/or etilefrine to oral diuretics therapy on serum sodium (Na) concentration in cirrhotic patients with ascites.
By measuring the final change in serum Na concentration (mEq/L) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). All blood samples were collected from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
Measured: 38 days (from the first day of the study to the end of the study)
Evaluate the effect of adding HSS infusion and/or etilefrine to oral diuretics therapy on serum creatinine concentration in cirrhotic patients with ascites.
By measuring the final change in serum creatinine concentration (mg/dl) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). All blood samples were collected for measuring from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
Measured: 38 days (from the first day of the study to the end of the study)

Secondary outcomes (12)

Evaluate the effect of adding HSS infusion and/or etilefrine to oral diuretics therapy on prothrombin concentration in cirrhotic patients with ascites.
By measuring the final change in prothrombin concentration (%) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). All blood samples were collected from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
Measured: 38 days (from the first day of the study to the end of the study)
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.
By calculating the final change in MELD score in patients with ascites to assess the severity of liver disease for transplant planning, from the first day of the study to the end of the study (study duration 38 days). MELD score calculation depends on serum creatinine, serum bilirubin, prothrombin time, and the score calculated by a suitable online medical calculator. All blood samples were collected for measuring from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
Measured: 38 days (from the first day of the study to the end of the study)
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.
By calculating the final change in MELD-Na score in patients with ascites from the first day of the study to the end of the study (study duration 38 days). MELD-Na score calculation depends on serum creatinine, serum bilirubin, serum Na, prothrombin time, and the score calculated by a suitable online medical calculator. All blood samples were collected for measuring from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
Measured: 38 days (from the first day of the study to the end of the study)
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.
By calculating the final change in Child-Pugh score in patients with ascites to assess the prognosis in liver cirrhosis from the first day of the study to the end of the study (study duration 38 days). Child-Pugh score calculation depends on serum albumin, serum bilirubin, prothrombin time, ascites, and encephalopathy grades. The score was calculated by a suitable online medical calculator. All blood samples were collected for measuring from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
Measured: 38 days (from the first day of the study to the end of the study)
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.
By calculating the final change in the patients' weight (kg) from the first day of the study to the end of the study (study duration 38 days). All enrolled patients were weighed by suitable weight scale on the morning of the first day of the study (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
Measured: 38 days (from the first day of the study to the end of the study)
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.
By measuring the final change in urinary Na concentration (mEq/24 hr) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). Urinary Na concentration was measured from a 24-hr urine collection sample. 24-hr urine was collected in the morning from 7 am to 7 am of the next day before initiation of the treatment (first measurement), after eight days of the treatment (second measurement), and after a month from the second measurement (third measurement).
Measured: 38 days (from the first day of the study to the end of the study)
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.
By measuring the final change in urinary creatinine concentration (mg/dl) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). 24-hr urine collected in the morning from 7 AM to 7 AM of the next day before initiation of the study to measure urinary creatinine concentration (first measurement), after eight days of treatment (second measurement), and after a month from the second measurement (third measurement).
Measured: 38 days (from the first day of the study to the end of the study)
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.
By measuring the final change in serum ALT (U/L) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). All blood samples were collected from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
Measured: 38 days (from the first day of the study to the end of the study)
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.
By measuring the final change in serum albumin (mg/dl) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). All blood samples were collected from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
Measured: 38 days (from the first day of the study to the end of the study)
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.
By measuring the final change in serum total bilirubin (mg/dl) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). All blood samples were collected from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
Measured: 38 days (from the first day of the study to the end of the study)
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.
By measuring the final change in serum BUN (mg/dl) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). All blood samples were collected from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
Measured: 38 days (from the first day of the study to the end of the study)
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.
By measuring the final change in hemoglobin concentration (gm/dl) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). All blood samples were collected from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
Measured: 38 days (from the first day of the study to the end of the study)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Nov 201730 Apr 2020

First posted8 Mar 2021
Study start30 Nov 2017
Primary completion21 Mar 2020
Study completion30 Apr 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (22)Papers the sponsor has linked to this study.
Other trials for Hepatic AscitesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 90 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04785755
Sponsor's protocol ID: ascites of liver cirrhosis
Status last verified: Mar 2021
First submitted: 26 Feb 2021
Last updated: 8 Mar 2021
Results posted: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Reynolds TB. Ascites. Clin Liver Dis. 2000 Feb;4(1):151-68, vii. doi: 10.1016/s1089-3261(05)70101-x.
PubMed 11232182
Gu XB, Yang XJ, Zhu HY, Xu BY. Effect of a diet with unrestricted sodium on ascites in patients with hepatic cirrhosis. Gut Liver. 2012 Jul;6(3):355-61. doi: 10.5009/gnl.2012.6.3.355. Epub 2012 Jul 12.
PubMed 22844565
Morando F, Rosi S, Gola E, Nardi M, Piano S, Fasolato S, Stanco M, Cavallin M, Romano A, Sticca A, Caregaro L, Gatta A, Angeli P. Adherence to a moderate sodium restriction diet in outpatients with cirrhosis and ascites: a real-life cross-sectional study. Liver Int. 2015 May;35(5):1508-15. doi: 10.1111/liv.12583. Epub 2014 May 21.
PubMed 24811138
Sam J, Nguyen GC. Protein-calorie malnutrition as a prognostic indicator of mortality among patients hospitalized with cirrhosis and portal hypertension. Liver Int. 2009 Oct;29(9):1396-402. doi: 10.1111/j.1478-3231.2009.02077.x. Epub 2009 Jul 7.
PubMed 19602136
Eghtesad S, Poustchi H, Malekzadeh R. Malnutrition in liver cirrhosis:the influence of protein and sodium. Middle East J Dig Dis. 2013 Apr;5(2):65-75.
PubMed 24829672
Arroyo V, Fernandez J. Relationship between systemic hemodynamics, renal dysfunction, and fluid retention in cirrhosis. Clin Liver Dis (Hoboken). 2013 Jun 21;2(3):120-122. doi: 10.1002/cld.185. eCollection 2013 Jun. No abstract available.
PubMed 30992841
Guo TT, Yang Y, Song Y, Ren Y, Liu ZX, Cheng G. Effects of midodrine in patients with ascites due to cirrhosis: Systematic review and meta-analysis. J Dig Dis. 2016 Jan;17(1):11-9. doi: 10.1111/1751-2980.12304.
PubMed 26630543
Singh V, Dhungana SP, Singh B, Vijayverghia R, Nain CK, Sharma N, Bhalla A, Gupta PK. Midodrine in patients with cirrhosis and refractory or recurrent ascites: a randomized pilot study. J Hepatol. 2012 Feb;56(2):348-54. doi: 10.1016/j.jhep.2011.04.027. Epub 2011 Jul 13.
PubMed 21749847
Hatanaka E, Shimomi FM, Curi R, Campa A. Sodium chloride inhibits cytokine production by lipopolysaccharide-stimulated human neutrophils and mononuclear cells. Shock. 2007 Jan;27(1):32-5. doi: 10.1097/01.shk.0000238061.69579.a5.
PubMed 17172977
Kolsen-Petersen JA. Immune effect of hypertonic saline: fact or fiction? Acta Anaesthesiol Scand. 2004 Jul;48(6):667-78. doi: 10.1111/j.1399-6576.2004.00396.x.
PubMed 15196097
Perez-Perez A, Vilarino-Garcia T, Fernandez-Riejos P, Martin-Gonzalez J, Segura-Egea JJ, Sanchez-Margalet V. Role of leptin as a link between metabolism and the immune system. Cytokine Growth Factor Rev. 2017 Jun;35:71-84. doi: 10.1016/j.cytogfr.2017.03.001. Epub 2017 Mar 4.
PubMed 28285098
Buechler C, Haberl EM, Rein-Fischboeck L, Aslanidis C. Adipokines in Liver Cirrhosis. Int J Mol Sci. 2017 Jun 29;18(7):1392. doi: 10.3390/ijms18071392.
PubMed 28661458
Reynolds TB, Lieberman FL, Goodman AR. Advantages of treatment of ascites without sodium restriction and without complete removal of excess fluid. Gut. 1978 Jun;19(6):549-53. doi: 10.1136/gut.19.6.549.
PubMed 680588
Lafreniere G, Beliveau P, Begin JY, Simonyan D, Cote S, Gaudreault V, Israeli Z, Lavi S, Bagur R. Effects of hypertonic saline solution on body weight and serum creatinine in patients with acute decompensated heart failure. World J Cardiol. 2017 Aug 26;9(8):685-692. doi: 10.4330/wjc.v9.i8.685.
PubMed 28932357
Henriksen JH, Fuglsang S, Bendtsen F, Moller S. Arterial hypertension in cirrhosis: arterial compliance, volume distribution, and central haemodynamics. Gut. 2006 Mar;55(3):380-7. doi: 10.1136/gut.2005.064329.
PubMed 16474108

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 8 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of Adding Hypertonic Saline Solutions and/or Etilefrine to Standard Diuretics Therapy in Egyptian Cirrhotic Patients With Ascites
ClinicalTrials.gov ID: NCT04785755
Acronym / sponsor ID: ascites of liver cirrhosis
Conditions: Hepatic Ascites
Keywords: Ascites, Hypertonic saline, Etilefrine, Aldosterone, Leptin.
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 90 participants (actual)
Lead sponsor: Hala Abd EL-Tawab Ibrahim RadwanUniversity, hospital or other
Study start: 30 Nov 2017 (actual)
Primary completion: 21 Mar 2020 (actual)
Study completion: 30 Apr 2020 (actual)
First posted: 8 Mar 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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:

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

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

Samples collection:

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Group I	Active comparator	Drug: Oral standard diuretics therapyThe 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 II	Experimental	Drug: Oral standard diuretics therapy, Drug: Hypertonic saline solutionThe 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 III	Experimental	Drug: Oral standard diuretics therapy, Drug: EtilefrineThe 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 IV	Experimental	Drug: Oral standard diuretics therapy, Drug: Hypertonic saline solution, Drug: EtilefrineThe 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).

Who may qualify

Ages: 25 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

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

Key exclusion criteria (7 listed)

Non-cirrhotic ascites.
Congestive heart failure.
Acute renal failure.
Hepatocellular carcinoma.
All Cancer types.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Oral standard diuretics therapyAlso: Furosemide (lasix®), Spironolactone (Aldactone®)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).	Drug	Group I, Group II, Group III, Group IV
Hypertonic saline solutionAlso: prepared from sodium chloride 0.9% intravenous solution and sodium chloride 3% intravenous solution (, Egypt Otsuka Pharmaceutical Co.).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.	Drug	Group II, Group IV
EtilefrineAlso: (Vascon®)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).	Drug	Group III, Group IV

Primary outcome

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.
Time frame: 38 days (from the first day of the study to the end of the study)
By measuring the final change in serum interleukin-6 (pg/ml) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). All blood samples were collected for measuring from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
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.
Time frame: 38 days (from the first day of the study to the end of the study)
By measuring the final change in serum C-reactive protein (mg/L) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). All blood samples were collected for measuring from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
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.
Time frame: 38 days (from the first day of the study to the end of the study)
By measuring the final change in serum leptin (pg/ml) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). All blood samples were collected for measuring from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
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.
Time frame: 38 days (from the first day of the study to the end of the study)
By measuring the final change in plasma aldosterone (pg/ml) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). All blood samples were collected for measuring from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
Evaluate and compare the impact of adding HSS infusion and/or etilefrine to oral diuretics therapy on the diuresis of cirrhotic patients with ascites.
Time frame: 38 days (from the first day of the study to the end of the study)
By measuring the final change in 24-hour urine output (ml/24 hr) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). 24-hr urine was collected in the morning from 7 am to 7 am of the next day before treatment (first collection), after eight days of treatment (second collection), and after a month from the second collection for assessing diuresis.
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.
Time frame: 38 days (from the first day of the study to the end of the study)
By measuring the effects of the treatments on mean arterial pressure (MAP) in patients with ascites. Systolic blood pressure (mmHg) and diastolic blood pressure (mmHg) were measured using a sphygmomanometer to calculate MAP first on day one of the treatments (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement). Final changes in MAP (mmHg) were calculated from the first day of the study to the end of the study (study duration 38 days)
Evaluate the effect of adding HSS infusion and/or etilefrine to oral diuretics therapy on serum sodium (Na) concentration in cirrhotic patients with ascites.
Time frame: 38 days (from the first day of the study to the end of the study)
By measuring the final change in serum Na concentration (mEq/L) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). All blood samples were collected from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).
Evaluate the effect of adding HSS infusion and/or etilefrine to oral diuretics therapy on serum creatinine concentration in cirrhotic patients with ascites.
Time frame: 38 days (from the first day of the study to the end of the study)
By measuring the final change in serum creatinine concentration (mg/dl) in patients with ascites from the first day of the study to the end of the study (study duration 38 days). All blood samples were collected for measuring from enrolled patients in the morning on the first day of treatment (first measurement), after eight days (second measurement), and after a month from the second measurement (third measurement).

12 secondary outcomes

Evaluate the effect of adding HSS infusion and/or etilefrine to oral diuretics therapy on prothrombin concentration in cirrhotic patients with ascites.
Time frame: 38 days (from the first day of the study to the end of the study)
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.
Time frame: 38 days (from the first day of the study to the end of the study)
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.
Time frame: 38 days (from the first day of the study to the end of the study)
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.
Time frame: 38 days (from the first day of the study to the end of the study)
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.
Time frame: 38 days (from the first day of the study to the end of the study)
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.
Time frame: 38 days (from the first day of the study to the end of the study)
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.
Time frame: 38 days (from the first day of the study to the end of the study)
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.
Time frame: 38 days (from the first day of the study to the end of the study)
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.
Time frame: 38 days (from the first day of the study to the end of the study)
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.
Time frame: 38 days (from the first day of the study to the end of the study)
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.
Time frame: 38 days (from the first day of the study to the end of the study)
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.
Time frame: 38 days (from the first day of the study to the end of the study)

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2021.
Results publication: PubMed 11232182Reynolds TB. Ascites. Clin Liver Dis. 2000 Feb;4(1):151-68, vii. doi: 10.1016/s1089-3261(05)70101-x.
Results publication: PubMed 22844565Gu XB, Yang XJ, Zhu HY, Xu BY. Effect of a diet with unrestricted sodium on ascites in patients with hepatic cirrhosis. Gut Liver. 2012 Jul;6(3):355-61. doi: 10.5009/gnl.2012.6.3.355. Epub 2012 Jul 12.
Results publication: PubMed 24811138Morando F, Rosi S, Gola E, Nardi M, Piano S, Fasolato S, Stanco M, Cavallin M, Romano A, Sticca A, Caregaro L, Gatta A, Angeli P. Adherence to a moderate sodium restriction diet in outpatients with cirrhosis and ascites: a real-life cross-sectional study. Liver Int. 2015 May;35(5):1508-15. doi: 10.1111/liv.12583. Epub 2014 May 21.
Results publication: PubMed 19602136Sam J, Nguyen GC. Protein-calorie malnutrition as a prognostic indicator of mortality among patients hospitalized with cirrhosis and portal hypertension. Liver Int. 2009 Oct;29(9):1396-402. doi: 10.1111/j.1478-3231.2009.02077.x. Epub 2009 Jul 7.
Results publication: PubMed 24829672Eghtesad S, Poustchi H, Malekzadeh R. Malnutrition in liver cirrhosis:the influence of protein and sodium. Middle East J Dig Dis. 2013 Apr;5(2):65-75.
Results publication: PubMed 30992841Arroyo V, Fernandez J. Relationship between systemic hemodynamics, renal dysfunction, and fluid retention in cirrhosis. Clin Liver Dis (Hoboken). 2013 Jun 21;2(3):120-122. doi: 10.1002/cld.185. eCollection 2013 Jun. No abstract available.
Results publication: PubMed 26630543Guo TT, Yang Y, Song Y, Ren Y, Liu ZX, Cheng G. Effects of midodrine in patients with ascites due to cirrhosis: Systematic review and meta-analysis. J Dig Dis. 2016 Jan;17(1):11-9. doi: 10.1111/1751-2980.12304.
Results publication: PubMed 21749847Singh V, Dhungana SP, Singh B, Vijayverghia R, Nain CK, Sharma N, Bhalla A, Gupta PK. Midodrine in patients with cirrhosis and refractory or recurrent ascites: a randomized pilot study. J Hepatol. 2012 Feb;56(2):348-54. doi: 10.1016/j.jhep.2011.04.027. Epub 2011 Jul 13.
Results publication: PubMed 17172977Hatanaka E, Shimomi FM, Curi R, Campa A. Sodium chloride inhibits cytokine production by lipopolysaccharide-stimulated human neutrophils and mononuclear cells. Shock. 2007 Jan;27(1):32-5. doi: 10.1097/01.shk.0000238061.69579.a5.
Results publication: PubMed 15196097Kolsen-Petersen JA. Immune effect of hypertonic saline: fact or fiction? Acta Anaesthesiol Scand. 2004 Jul;48(6):667-78. doi: 10.1111/j.1399-6576.2004.00396.x.
Results publication: PubMed 28285098Perez-Perez A, Vilarino-Garcia T, Fernandez-Riejos P, Martin-Gonzalez J, Segura-Egea JJ, Sanchez-Margalet V. Role of leptin as a link between metabolism and the immune system. Cytokine Growth Factor Rev. 2017 Jun;35:71-84. doi: 10.1016/j.cytogfr.2017.03.001. Epub 2017 Mar 4.
Results publication: PubMed 28661458Buechler C, Haberl EM, Rein-Fischboeck L, Aslanidis C. Adipokines in Liver Cirrhosis. Int J Mol Sci. 2017 Jun 29;18(7):1392. doi: 10.3390/ijms18071392.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gamal A Badra, professor study director

national liver institute / menoufiya university

Sahar El-Haggar, professor study director

Tanta University

hala El said, professor study director

national liver institute / menoufiya university

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Oral standard diuretics therapy, Hypertonic saline solution and Etilefrine in people with Hepatic Ascites, run by Hala Abd EL-Tawab Ibrahim Radwan at 1 site in Egypt.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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. (time frame: 38 days (from the first day of the study to the end of the study)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04785755, which also lists 22 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2021.