Refractory Ascitis Diagnosis by the Study of Labelled Albumin Pharmacokinetics

Refractory Ascites in Patients With Cirrhosis Clinical Trial

— ARAM  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02818673
• Other study ID #: P140902
• Secondary ID: 2015-000157-20
• Status: Not yet recruiting
• Phase: Phase 3
• First received: June 20, 2016
• Last updated: June 13, 2017
• Start date: September 2017
• Est. completion date: January 2020

Study information

• Verified date: June 2017
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: VALLA Dominique, MD
• Phone: 06 09 17 81 28
• Email: dominique.valla[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: January 2020
• Est. primary completion date: November 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Ascites
• Refractory Ascites in Patients With Cirrhosis

Intervention

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
• 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

Locations

Country	Name	City	State
France	Hôpital Beaujon	Clichy

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diagnosis of refractory ascitis according to International Ascites Club (IAC)		Exploration day (4 weeks after the inclusion)
Secondary	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)
Secondary	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)
Secondary	Measure of pharmacokinetics parameters	Ratio TPA/TAP	Exploration day (4 weeks after the inclusion)
Secondary	adverse events	Phone call	1 month after exploration day
Secondary	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)