Refractory Ascitis Diagnosis by the Study of Labelled Albumin Pharmacokinetics (ARAM)

Refractory Ascitis Diagnosis by the Study of Labelled Albumin Pharmacokinetics Between Peritoneal and Vascular Compartments

Refractory ascites is an indication for liver transplantation, and includes ascites that is resistant to, or intractable by diuretic therapy (International Ascites Club). This definition is partly subjective; it can be established only a posteriori, following diuretic therapy administration to all patients, including those in whom untoward effects are prominent; and requires prolonged follow-up. An early diagnosis of refractory ascites would avoid giving diuretic therapy to patients in whom it will fail and identify rapidly candidates to liver transplantation. Such diagnosis could be done with a pharmacokinetic (PK) study of radiolabeled albumin between the peritoneal cavity and serum.

Study Overview

• Status: Unknown
• Conditions: Refractory Ascites in Patients With Cirrhosis
• Intervention / Treatment: Radiation: labelled human serumalbumin (125-I, Séralb®CisBio); Radiation: labelled albumin (99m-Tc, Vasculocis®, Cisbio)

Detailed Description

Main objective: assess the performances of PK parameters (transfer of labelled albumin) between peritoneal and vascular compartments, for the diagnosis of refractory ascitis, in patients with cirrhosis and abundant ascitis.

Design: proof of concept study. Interventional cross-sectional study in Beaujon Hospital (Clichy, France), 1 recruiting center and 1 non recruiting center.

Patients are recruited in the Hepatology department (Pr Valla) and PK exploration is performed in the nuclear medicine department (Pr Lebtahi) of Beaujon Hospital.

Description of intervention: diuretics treatment discontinuation 7 days before exploration for patients with sensitive ascitis, and more than 7 days for those with refractory ascitis. The day of exploration, the patients come to hospital and stay in lying position. One intra-veinous injection of 0,015 megabecquerel(MBq) /Kg labelled human serum albumin (Iode-125 (125-I), Séralb®CisBio), in compliance with market authorization, simultaneously to one intra-peritoneal injection of 200 MBq of labelled albumin (Technetium 99m (99m-Tc), Vasculocis®, Cisbio), off-label used. It follows 5 minutes mobilization of the patient (right and left lateral decubitus), then a scintigraphy will be performed using a gamma-camera Symbia T2 (Siemens®). Repeated blood (5 ml) and peritoneal ascitis (3 ml) samples are performed before injection and every 30 minutes for 6 hours (catheter in place). Diuretic treatment can be restarted the day after PK explorations. Patients are followed-up at 1 month by phone call (for the collection of adverse events).

Measurements : radioactivity measurements of 99m-Tc and 125-I in the biological samples are performed by a counter device in the nuclear medicine department (Wizard 3000, Packard®). Unidirectional transfer of labelled albumin (125-I) from vascular compartment (plasma-P) to peritoneal compartment (ascitis-A) (TPA), Unidirectional transfer of labelled albumin (99m-Tc) from peritoneal (A) to vascular compartment (P) (TAP), and the ratio TPA/TAP are calculated from these measurements using Matlab®.The gold standard is defined by the diagnosis of refractory ascitis performed before inclusion.

Statistical analyses: performances of the TAP, of the TPA, and of the ratio TPA/TAP for the diagnosis of refractory ascitis, will be computed using the Receiver Operating Characteristic (ROC) curve.

Number of patients : 30 patients (15 patients with refractory ascitis and 15 patients with sensitive or untreatable ascitis) will be included during a 24 months period (1 or 2 patients per month), and followed-up for 2 months. The PK explorations will be performed in nuclear medicine department not more than 4 weeks after inclusion. Total length of study will be of 26 months.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Clichy, France, 92110
    • Hôpital Beaujon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients consulting in Hepatology department of Beaujon Hospital
• aged 18 - 80 years old
• cirrhosis due to alcoholic and/or dysmetabolic and/or viral (HBV or HCV) cause, pathologically or clinically/biologically/radiologically proven.
• Volume of ascitis >5 L, either sensible or refractory to diuretics drugs according IAC criteria

Exclusion Criteria:

• infection in the 2 weeks prior to inclusion (suspected or proven)
• upper gastrointestinal bleeding du to portal hypertension in the 2 weeks prior to inclusion
• transjugular intrahepatic portosystemic shunt (TIPS)
• advanced hepatocellular carcinoma
• hepatic transplantation
• unability to stay lying for 6 hours
• pregnancy / lactation
• renal deficiency (creat. clearance < 60ml/min)
• cardiac deficiency (≥ New York Heart Association (NYHA) III) or myocardial infarction (<3 months)
• other cause of ascitis
• contra-indication to human albumin (125-I) or vasculosis (99m-Tc) or other component of radio-pharmaceutics
• no health insurance coverage
• unability to go to the hospital for 1 day of exams
• refuse to consent to study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ascites in Patients With Cirrhosis; Patients will be further classified according to the refractory or sensitive ascitis	Radiation: labelled human serumalbumin (125-I, Séralb®CisBio); Intra-veinous injection of 0,015 MBq/Kg ; 0,5 to 2 mL injected over less than a minute; Radiation: labelled albumin (99m-Tc, Vasculocis®, Cisbio); intra-peritoneal injection of 200 MBq of labelled albumin (99m-Tc, Vasculocis®, Cisbio) ; 5 ml injected over less than a minute

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Diagnosis of refractory ascitis according to International Ascites Club (IAC)	Exploration day (4 weeks after the inclusion)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of pharmacokinetics parameters : TPA	radioactivity measurements of labelled albumin (125-I) in ascitis (peritoneal samples) and plasma (blood samples)	Exploration day (4 weeks after the inclusion)
Measure of pharmacokinetics parameters : TAP	radioactivity measurements of labelled albumin (99m-Tc) in ascitis (peritoneal samples) and plasma (blood samples)	Exploration day (4 weeks after the inclusion)
Measure of pharmacokinetics parameters	Ratio TPA/TAP	Exploration day (4 weeks after the inclusion)
adverse events	Phone call	1 month after exploration day
Proportion of patients in whom examination conditions and technical feasibility were completed	adequate volume of ascites,stable state of patient, satisfactory spread of radiopharmaceuticals in the peritoneal compartment measure by scintigraphy, number of peritoneal and blood samples performed	Exploration day (4 weeks after the inclusion)

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: VALLA Dominique, MD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2017
• Primary Completion (Anticipated): November 1, 2019
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: June 20, 2016
• First Submitted That Met QC Criteria: June 27, 2016
• First Posted (Estimate): June 30, 2016

Study Record Updates

• Last Update Posted (Actual): June 15, 2017
• Last Update Submitted That Met QC Criteria: June 13, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: ascites; diagnostic performances
• Additional Relevant MeSH Terms: Pathologic Processes; Ascites
• Other Study ID Numbers: P140902; 2015-000157-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No