Refractory Ascitis Diagnosis by the Study of Labelled Albumin Pharmacokinetics (ARAM)
Primary Purpose
Refractory Ascites in Patients With Cirrhosis
Status
Unknown status
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
labelled human serumalbumin (125-I, Séralb®CisBio)
labelled albumin (99m-Tc, Vasculocis®, Cisbio)
Sponsored by
About this trial
This is an interventional diagnostic trial for Refractory Ascites in Patients With Cirrhosis focused on measuring diagnostic performances, ascites
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
Sites / Locations
- Hôpital Beaujon
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ascites in Patients With Cirrhosis
Arm Description
Patients will be further classified according to the refractory or sensitive ascitis
Outcomes
Primary Outcome Measures
Diagnosis of refractory ascitis according to International Ascites Club (IAC)
Secondary Outcome Measures
Measure of pharmacokinetics parameters : TPA
radioactivity measurements of labelled albumin (125-I) in ascitis (peritoneal samples) and plasma (blood samples)
Measure of pharmacokinetics parameters : TAP
radioactivity measurements of labelled albumin (99m-Tc) in ascitis (peritoneal samples) and plasma (blood samples)
Measure of pharmacokinetics parameters
Ratio TPA/TAP
adverse events
Phone call
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
Full Information
NCT ID
NCT02818673
First Posted
June 20, 2016
Last Updated
June 13, 2017
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT02818673
Brief Title
Refractory Ascitis Diagnosis by the Study of Labelled Albumin Pharmacokinetics
Acronym
ARAM
Official Title
Refractory Ascitis Diagnosis by the Study of Labelled Albumin Pharmacokinetics Between Peritoneal and Vascular Compartments
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Unknown status
Study Start Date
September 2017 (Anticipated)
Primary Completion Date
November 2019 (Anticipated)
Study Completion Date
January 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Ascites in Patients With Cirrhosis
Keywords
diagnostic performances, ascites
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Ascites in Patients With Cirrhosis
Arm Type
Experimental
Arm Description
Patients will be further classified according to the refractory or sensitive ascitis
Intervention Type
Radiation
Intervention Name(s)
labelled human serumalbumin (125-I, Séralb®CisBio)
Intervention Description
Intra-veinous injection of 0,015 MBq/Kg ; 0,5 to 2 mL injected over less than a minute
Intervention Type
Radiation
Intervention Name(s)
labelled albumin (99m-Tc, Vasculocis®, Cisbio)
Intervention Description
intra-peritoneal injection of 200 MBq of labelled albumin (99m-Tc, Vasculocis®, Cisbio) ; 5 ml injected over less than a minute
Primary Outcome Measure Information:
Title
Diagnosis of refractory ascitis according to International Ascites Club (IAC)
Time Frame
Exploration day (4 weeks after the inclusion)
Secondary Outcome Measure Information:
Title
Measure of pharmacokinetics parameters : TPA
Description
radioactivity measurements of labelled albumin (125-I) in ascitis (peritoneal samples) and plasma (blood samples)
Time Frame
Exploration day (4 weeks after the inclusion)
Title
Measure of pharmacokinetics parameters : TAP
Description
radioactivity measurements of labelled albumin (99m-Tc) in ascitis (peritoneal samples) and plasma (blood samples)
Time Frame
Exploration day (4 weeks after the inclusion)
Title
Measure of pharmacokinetics parameters
Description
Ratio TPA/TAP
Time Frame
Exploration day (4 weeks after the inclusion)
Title
adverse events
Description
Phone call
Time Frame
1 month after exploration day
Title
Proportion of patients in whom examination conditions and technical feasibility were completed
Description
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
Time Frame
Exploration day (4 weeks after the inclusion)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
VALLA Dominique, MD
Phone
06 09 17 81 28
Ext
+33
Email
dominique.valla@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
VALLA Dominique, MD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Beaujon
City
Clichy
ZIP/Postal Code
92110
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
VALLA Dominique, MD
Email
dominique.valla@aphp.fr
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Refractory Ascitis Diagnosis by the Study of Labelled Albumin Pharmacokinetics
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