Refractory Ascitis Diagnosis by the Study of Labelled Albumin Pharmacokinetics

NCT ID: NCT02818673

Last Updated: 2017-06-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-30
• Study Completion Date: 2020-01-31

Brief Summary

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.

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.

Conditions

Refractory Ascites in Patients With Cirrhosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Ascites in Patients With Cirrhosis

Patients will be further classified according to the refractory or sensitive ascitis

Group Type: EXPERIMENTAL

labelled human serumalbumin (125-I, Séralb®CisBio)

Intervention Type: RADIATION

Intra-veinous injection of 0,015 MBq/Kg ; 0,5 to 2 mL injected over less than a minute

labelled albumin (99m-Tc, Vasculocis®, Cisbio)

Intervention Type: RADIATION

intra-peritoneal injection of 200 MBq of labelled albumin (99m-Tc, Vasculocis®, Cisbio) ; 5 ml injected over less than a minute

Interventions

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

Intervention Type: 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

Intervention Type: RADIATION

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

VALLA Dominique, MD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Hôpital Beaujon

Clichy, , France

Countries

France

Central Contacts

VALLA Dominique, MD

Role: CONTACT

dominique.valla@aphp.fr

06 09 17 81 28 ext. +33

Facility Contacts

VALLA Dominique, MD

Role: primary

dominique.valla@aphp.fr

Other Identifiers

2015-000157-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

P140902

Identifier Type: -

Identifier Source: org_study_id