NCT02821377

Brief Summary

Introduction: Patients with chronic liver diseases are usually thin as a result of hypermetabolism and malnutrition expressed by reduced levels of leptin and impairment of other adyponectins such as visfatin. Aims: To evaluate the metabolic and inflammatory effects of intravenous high-dose furosemide plus hypertonic saline solutions (HSS) compared with repeated paracentesis and a standard oral diuretic schedule, in patients with cirrhosis and refractory ascites. Methods; All consecutive cirrhotic patients with refractory ascites unresponsive to outpatient treatment will be enrolled . Enrolled subjects will be randomized to treatment with intravenous infusion of furosemide (125-250mg⁄bid) plus small volumes of HSS from the first day after admission until 3 days before discharge (Group A ), or repeated paracentesis from the first day after admission until 3 days before discharge (Group B, ). Plasma levels of ANP, BNP, Leptin, visfatin, IL-1β, TNF-a, IL-6 were measured before and after the two type of treatment.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Dec 2013

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2013

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2015

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2016

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

June 23, 2016

Completed
8 days until next milestone

First Posted

Study publicly available on registry

July 1, 2016

Completed
Last Updated

July 1, 2016

Status Verified

June 1, 2016

Enrollment Period

2 years

First QC Date

June 23, 2016

Last Update Submit

June 30, 2016

Conditions

AscitesCirrhosis

Keywords

cirrhosisascitesimmunologyinflammationnutrition

Outcome Measures

Primary Outcomes (1)

  • Δ-ANP

    difference between ANP serum levels at admission and ANP serum levels at discharge.

    8 days

Secondary Outcomes (6)

  • Δ-BNP (pg/ml): evaluated by means of the difference between BNP plasma levels at admission and BNP plasma levels at discharge.

    8 days

  • Δ IL-1beta (pg/ml): evaluated by means of the difference between IL-1beta plasma levels at admission and IL-1beta plasma levels at discharge.

    8 days

  • Δ-visfatin (ng/ml): evaluated by means of the difference between serum visfatin at admission and serum visfatin at discharge.

    8 days

  • Δ-Leptin (ng/ml): evaluated by means of the difference between serum leptin at admission and serum leptin at discharge.

    8 days

  • Δ-TNF-alfa (ng/ml): evaluated by means of the difference between serum TNF-alfa at admission and serum TNF-alfa discharge.

    8 days

  • +1 more secondary outcomes

Study Arms (3)

intravenous furosemide

EXPERIMENTAL

intravenous infusion of furosemide (doses 125-250mg⁄ bid) from the first day after admission until 3 days before discharge Intervention: drug: furosemide ; other name: lasix

Drug: intravenous furosemideDrug: Hypertonic saline solutions

intravenous hypertonic saline solutions

EXPERIMENTAL

small volumes of hypertonic saline solutions (HSS) (150mL 1.4-4.6% NaCl), from the first day after admission until 3 days before discharge Intervention: Hypertonic saline solutions (1.4-4.6%NaCl) Intervention other name: not specified

Drug: intravenous furosemideDrug: Hypertonic saline solutions

seriated paracentesis

ACTIVE COMPARATOR

no intervention Intervention: no drug only seriated paracentesis repeated paracentesis from the first day after admission until 3 days before discharge

Procedure: Seriated paracentesis

Interventions

intravenous furosemideDRUG

treatment with intravenous infusion of furosemide (doses 125-250mg⁄ bid) plus small volumes of HSS (150mL 1.4-4.6% NaCl), from the first day after admission until 3 days before discharge, with water restriction and a normal sodium diet.

Also known as: furosemide +HSS
intravenous furosemideintravenous hypertonic saline solutions
Hypertonic saline solutionsDRUG

Intravenous small volumes of HSS (150mL 1.4-4.6% NaCl), plus treatment with intravenous infusion of furosemide (doses 125-250mg⁄ bid) from the first day after admission until 3 days before discharge, with water restriction and a normal sodium diet.

Also known as: HSS
intravenous furosemideintravenous hypertonic saline solutions
Seriated paracentesisPROCEDURE

repeated paracentesis from the first day after admission until 3 days before discharge

Also known as: paracentesis
seriated paracentesis

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Refractory ascites defined according to the International Ascites Club criteria

You may not qualify if:

  • inability to obtain informed consent
  • possible non-cirrhotic ascites
  • congestive heart failure (defined by clinical exam and echocardiogram)
  • acute renal failure
  • hepatocellular carcinoma based on the Barcelona Clinic liver Cancer (BCLC) criteria
  • complete portal vein thrombosis, active sepsis or other incurable cancers

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Antonino Tuttolomondo

Palermo, Italy, 90127, Italy

Location

Internal Medicine Ward of Palermo University Hospital

Palermo, Italy, 90127, Italy

Location

Internal Medicine Ward, University of Palermo

Palermo, Italy, 90127, Italy

Location

Related Publications (2)

  • Licata G, Tuttolomondo A, Licata A, Parrinello G, Di Raimondo D, Di Sciacca R, Camma C, Craxi A, Paterna S, Pinto A. Clinical Trial: High-dose furosemide plus small-volume hypertonic saline solutions vs. repeated paracentesis as treatment of refractory ascites. Aliment Pharmacol Ther. 2009 Aug;30(3):227-35. doi: 10.1111/j.1365-2036.2009.04040.x. Epub 2009 May 12.

    PMID: 19438847BACKGROUND

  • Tuttolomondo A, Pinto A, Di Raimondo D, Corrao S, Di Sciacca R, Scaglione R, Caruso C, Licata G. Changes in natriuretic peptide and cytokine plasma levels in patients with heart failure, after treatment with high dose of furosemide plus hypertonic saline solution (HSS) and after a saline loading. Nutr Metab Cardiovasc Dis. 2011 May;21(5):372-9. doi: 10.1016/j.numecd.2009.10.014. Epub 2010 Mar 25.

    PMID: 20346637BACKGROUND

MeSH Terms

Conditions

AscitesFibrosisInflammation

Interventions

Saline Solution, HypertonicParacentesis

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hypertonic SolutionsSolutionsPharmaceutical PreparationsSpecimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisDrainageTherapeuticsPuncturesSurgical Procedures, OperativeInvestigative Techniques

Study Officials

  • Antonio Pinto, MD

    University of Palermo

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD, Associate Professor

Study Record Dates

First Submitted

June 23, 2016

First Posted

July 1, 2016

Study Start

December 1, 2013

Primary Completion

December 1, 2015

Study Completion

April 1, 2016

Last Updated

July 1, 2016

Record last verified: 2016-06

Data Sharing

IPD Sharing
Will not share

Locations

IT(3)