Clinical trial NCT02818673: Refractory Ascitis Diagnosis by the Study of Labelled Albumin Pharmacokinetics
Official title: Refractory Ascitis Diagnosis by the Study of Labelled Albumin Pharmacokinetics Between Peritoneal and Vascular Compartments
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Refractory Ascites in Patients With Cirrhosis
Keywords: diagnostic performances
ascites
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2016-06-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Diagnosis of refractory ascitis according to International Ascites Club (IAC)
timeFrame: Exploration day (4 weeks after the inclusion)
Secondary outcomes:
measure: Measure of pharmacokinetics parameters : TPA
timeFrame: Exploration day (4 weeks after the inclusion)
measure: Measure of pharmacokinetics parameters : TAP
timeFrame: Exploration day (4 weeks after the inclusion)
measure: Measure of pharmacokinetics parameters
timeFrame: Exploration day (4 weeks after the inclusion)
measure: adverse events
timeFrame: 1 month after exploration day
measure: Proportion of patients in whom examination conditions and technical feasibility were completed
timeFrame: Exploration day (4 weeks after the inclusion)
Other outcomes:
Locations:
city: Clichy
country: France
facility: Hôpital Beaujon
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: VALLA Dominique, MD
role: PRINCIPAL_INVESTIGATOR
References: