Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000321448
Ethics application status
Approved
Date submitted
26/12/2015
Date registered
10/03/2016
Date last updated
10/03/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Outpatient Terlipressin Infusion for the Treatment of Refractory Ascites.
Scientific title
Outpatient Terlipressin Infusion for the Treatment of Refractory Ascites.
Secondary ID [1] 288221 0
Nil Known
Universal Trial Number (UTN)
U1111-1177-9714
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ascites 297132 0
Portal Hypertension 297133 0
Diuretic refractory ascites 297134 0
Cirrhosis 297277 0
Condition category
Condition code
Oral and Gastrointestinal 297364 297364 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patient were admitted to hospital for placement of a peripherally inserted central cannula (PICC) line.
A terlipressin (Lucassin Registered Trademark ) infusion was commenced (1.7mg/12 hours via a syringe driver and subjects were observed in hospital for 24 hours to confirm tolerability.
The following day they were discharged home on an ambulatory terlipressin infusion which was then continued for 28 days.
Hospital-in-the-home nursing staff would visit each patient twice a day to exchange the terlipressin infusion syringe(1.7mg/12 hours) and monitor for adverse events and ensure medication delivery.
Intervention code [1] 293514 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 296917 0
Composite primary outcome: Safety and Practicality of administering a terlipressin infusion at home for a prolonged period of time in patients with refractory ascites. The safety of administration is based on the absence of adverse effects from the terlipressin infusion as symptoms suggestive of ischaemia as chest pain, abdominal pain or digit pain or discolouration. Practicality was based on answering a questionnaire,designed specifically for the study, of impact on mobility or personal activities of daily living.
Timepoint [1] 296917 0
Weekly for 4 weeks at each visit.
Primary outcome [2] 296918 0
Change in volume of ascites drained with terlipressin infusion. Patienst would have weekly ultrasounds to assess whether paracentesis can be performed safely and if so paracentesis would be performed to drain the ascites. The volume would be measured.
Timepoint [2] 296918 0
Assessed weekly for 4 weeks at each visit.
Primary outcome [3] 297037 0
Body weight change with terlipressin infusion compared to baseline body weight. Patients were weighed using the same weighing scale in the ambulatory care centre during their weekly review. Weight would be measured prior to paracentesis.
Timepoint [3] 297037 0
Weekly for 4 weeks at each visit
Secondary outcome [1] 319690 0
24 urine sodium excretion
Timepoint [1] 319690 0
Weekly for 4 weeks at each visit.
Secondary outcome [2] 319691 0
serum creatinine
Timepoint [2] 319691 0
Weekly for 4 weeks at each visit.
Secondary outcome [3] 319692 0
serum sodium
Timepoint [3] 319692 0
Weekly for 4 weeks at each visit.
Secondary outcome [4] 319693 0
Model of end stage liver disease (MELD)
Timepoint [4] 319693 0
Weekly for 4 weeks at each visit.
Secondary outcome [5] 319694 0
Serum Aldosterone levels.
Timepoint [5] 319694 0
Weekly for 4 weeks at each visit.

Eligibility
Key inclusion criteria
Inclusion criteria were refractory ascites secondary to cirrhosis requiring at least fortnightly large volume paracentesis and age greater than 18. It was also necessary for patient’s to have a stable therapeutic paracentesis frequency for at least 3 months.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria were: acute coronary syndrome within the past 6 months of enrolment or ongoing angina, prior intolerance to terlipressin, spontaneous bacterial peritonitis in the last 1 month, hepatic vein thrombosis or acute portal vein thrombosis, change in the dose of diuretics within the 30 days preceding the study or anemia with a hemoglobin below 70 mg/dl. The study was approved by the local Human Research Ethics Committee (HREC) and all patients provided written informed consent to participate.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This study is a proof of concept study and we were given funding for five patients. Each individual patient was compared before and after commencement of the study medication to assess for the primary and secondary outcomes.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
14/07/2015
Date of last participant enrolment
Anticipated
Actual
24/08/2015
Date of last data collection
Anticipated
Actual
Sample size
Target
5
Accrual to date
Final
5
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 4996 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 12482 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 292607 0
Charities/Societies/Foundations
Name [1] 292607 0
Austin Medical research Foundation
Country [1] 292607 0
Australia
Primary sponsor type
Individual
Name
Paul Gow
Address
Austin Health
Gastroenterology and liver transplant unit
145 studley Road
Heidelberg
3084
Victoria
Country
Australia
Secondary sponsor category [1] 291327 0
None
Name [1] 291327 0
None
Address [1] 291327 0
None
Country [1] 291327 0
Other collaborator category [1] 278749 0
Individual
Name [1] 278749 0
Zaid Ardalan
Address [1] 278749 0
Austin Health
Gastroenterology and liver transplant unit
145 studley road
Heidelberg
Victoria
3031
Country [1] 278749 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294088 0
Austin Human Research Ethics Committee (HREC).
Ethics committee address [1] 294088 0
145 studley road
Heidelberg
Victoria
3084
Ethics committee country [1] 294088 0
Australia
Date submitted for ethics approval [1] 294088 0
24/05/2014
Approval date [1] 294088 0
22/06/2015
Ethics approval number [1] 294088 0
HREC/14/Austin/266

Summary
Brief summary
Although most patients with cirrhosis complicated by ascites initially respond to salt restriction and diuretics, as their liver disease progresses many lose diuretic responsiveness and develop refractory ascites, a condition for which there is no established drug treatment. Terlipressin is a synthetic analogue of vasopressin that causes splanchnic vasoconstriction, consequently improving renal blood flow and kidney function, and thus may ameliorate many of the pathophysiological changes that result in ascites formation. Its short half-life and bolus dose administration have previously precluded its long term use to treat ascites or other complications of cirrhosis. We performed a 4 week prospective trial of outpatient continuous terlipressin infusion in 5 patients with refractory ascites to examine its safety, practicality and efficacy in reducing ascites formation.
Trial website
Trial related presentations / publications
NA
Public notes

Contacts
Principal investigator
Name 62406 0
Dr Zaid Ardalan
Address 62406 0
Austin Health
Gastroenterology and liver transplant unit
145 studley road
heidelberg
3084
Victoria
Country 62406 0
Australia
Phone 62406 0
+61432275953
Fax 62406 0
Email 62406 0
[email protected]
Contact person for public queries
Name 62407 0
Dr Zaid Ardalan
Address 62407 0
Austin Health
Gastroenterology and liver transplant unit
145 studley road
heidelberg
3084
Victoria
Country 62407 0
Australia
Phone 62407 0
+61432275953
Fax 62407 0
Email 62407 0
[email protected]
Contact person for scientific queries
Name 62408 0
Dr Paul Gow
Address 62408 0
Austin Health
Gastroenterology and liver transplant unit
145 studley road
heidelberg
3084
Victoria
Country 62408 0
Australia
Phone 62408 0
+61432275953
Fax 62408 0
Email 62408 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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