Peritoneal Dialysis Catheters for the Treatment of Refractory Ascites

Liver Cirrhosis Clinical Trial

Official title:

Peritoneal Dialysis Catheters for the Treatment of Refractory Ascites Management: A Randomized Un-Blinded Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02975726
• Other study ID #: B2014:066
• Status: Completed
• Phase: N/A
• Start date: January 2017
• Est. completion date: February 2019

Study information

• Verified date: April 2021
• Source: University of Manitoba
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

One complication of liver disease is the buildup of fluid within the belly. This is known as ascites. Patients who have ascites have a decreased appetite, pain, nausea and shortness of breath. Ascites is typically treated with medications, however when that does not work, patients need a procedure where a needle is inserted in the belly every few weeks to drain the excess fluid. About 2 in 5 patients with ascites from liver failure can get kidney disease from their worsening liver function or from the drainage of fluid with needles. Once patients have both advanced liver disease and kidney disease, their chance of dying largely increases.

The present study will be the first of its kind to study a new technique to treat ascites. Investigators are planning to place a tube in a patient's belly to drain the excessive amounts of fluid. This technique is similar to how one type of dialysis is done to treat patients with kidney failure. This study is set as a pilot investigation in order to determine the feasibility of doing a larger, randomized clinical trial investigating the use of this novel technique. Importantly, advanced liver disease patients are at high risk to develop kidney disease, and therefore are an important group to focus on. Investigators believe that this technique will prevent or slow the development of kidney disease in liver failure patients, and improve their quality of life, far more than the current available treatments.

Description:

Refractory ascites is when fluid recurrently accumulates in the peritoneal cavity, as an end result of multiple mechanisms, including liver cirrhosis, peritoneal infiltration by tumor, portal hypertension, lymphangitic carcinomatosis, congestive heart failure, or lymphatic obstruction. It is associated with increased mortality and morbidity, including complications of abdominal wall hernias, spontaneous bacterial peritonitis, kidney dysfunction, and pleural effusions. The development of ascites also leads to multiple symptoms including anorexia, early satiety, nausea and vomiting, shortness of breath, and limited mobility.

The management of ascites associated with liver dysfunction usually follows a stepwise escalation in treatments. The initial management typically involves sodium restriction and diuretic therapy up to a daily maximum of 160 mg of furosemide and 400 mg of spironolactone. When ascites no longer can be controlled by these measures, one option is to decrease portal hypertension, a main pathogenic factor in ascites development, by undergoing a procedure called transjugular intrahepatic portosystemic shunt (TIPS). This procedure requires certain patient criteria to be fulfilled and is associated with complications and increased risk of hepatic encephalopathy, and therefore is confined to a small subgroup of patients with ascites. Consequently, abdominal large volume paracentesis (LVP) is the treatment of choice in many patients. This procedure involves insertion of a needle into the peritoneal cavity where ascites accumulates, then attaching the needle to a collection system that drains the ascites by gravity. The definitive treatment for ascites in patients with cirrhosis is a liver transplant, but due to limited supply of organs, and contraindications to transplantation, patients often undergo repeated LVP while waiting on the wait list or until death. Paracentesis is associated with risks including post paracentesis circulatory dysfunction leading to hyponatremia, kidney dysfunction, viscus puncture, and peritonitis. It also is a costly, resource intense, and at times an uncomfortable treatment for patients due to the procedure itself and the need for repeated treatments.

A potential alternative to LVP is the placement of an intraperitoneal catheter, in the same manner that a peritoneal dialysis (PD) catheter, to drain ascites. The procedure has a high technical insertion success rate with minimal complications and is routinely done at the bedside by nephrologist under local anesthesia. PD catheter placement for ascites drainage has many potential advantages, including the ability for it to be done at home by the patient and avoid visits to clinics or hospitals; the frequency of drainage can be timed to patient symptoms, and perhaps have less complication rates than LVP. However, the efficacy and safety of this approach in decompensated cirrhosis when compared to periodic LVP (current standard of care) has not been tested in a randomized trial. Investigators propose a single center, multi-site randomized control trial comparing bedside PD catheter placement versus usual standard of serial LVP for treatment of refractory ascites. The primary outcomes will be improvement of 10 points in the physical component score (PCS) of the Short Form-36 (SF-36) at two months. Investigators plan to randomize 50 patients (25 per arm) based on a power calculation to achieve an 10 point improvement in the PCS-SF-36 (SE = 5). Secondary outcomes will include incidence of mechanical and infectious complications, emergency department utilization, hospitalization and mortality, all other domains of the SF-36, Euroquol-5D (EQ-5D), the Newcastle Patient Reported Ascites Measure and overall health care costs.

Primary Hypothesis: Drainage of ascites associated with liver failure via PD catheter is superior to serial LVP in improving the physical component of quality of life as measured by SF-36.

This trial will be pivotal in possibly changing the standard of care for the management of refractory ascites from cirrhosis. If the primary hypothesis is confirmed, investigators will design and conduct subsequent trials to address potential morbidity and mortality benefits associated with this technique for ascites management.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Est. completion date: February 2019
• Est. primary completion date: May 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Males and non-pregnant females greater than 18 years of age.

2. Liver cirrhosis as defined by a histological, clinical, or radiological criteria

3. Patients with refractory non-malignant ascites requiring 2 or more LVPs in the last 4 months.

4. No contraindication for bedside PD catheter insertion (e.g. prior major abdominal surgery, ostomies, large hernias, bleeding diatheses, inability to lie flat).

5. Patients having a support person (family member/friend/caregiver, etc) willing to go through training and help with catheter care.

Exclusion Criteria:

1. Prior liver transplant

2. Is actively being worked up for liver transplant or is already on the liver transplant waitlist

3. Current SBP (spontaneous bacterial peritonitis) defined as polymorphonuclear (PMN) cell count of >250 cells/mm3 in the ascites or positive bacteria in ascitic cultures

4. Malignant ascites

5. Severe coagulopathy with either an INR (international normalized ratio) > 1.5, a platelet count < 50 x 109/L that is not able to be reversed at time of PD catheter insertion

6. Any previous episodes of spontaneous bacterial peritonitis.

7. Loculated ascites

8. Known presence of HIV/AIDS

9. Immunomodulatory treatments used within the last 4 months

10. Expected survival <6 months and/or MELD (The Model for End-Stage Liver Disease) score > 30

11. Hepatic Encephalopathy episode requiring hospital admission in the past 6 months.

12. History of non-compliance or suspected failure to comply with study requirements

13. Allergies to Vancomycin and Cephalosporins.

Related Conditions & MeSH terms

• Ascites
• Fibrosis
• Liver Cirrhosis

Intervention

Device:
• Peritoneal Dialysis Catheter
Peritoneal dialysis catheter insertion in order to drain access fluid within the belly for patients with liver cirrhosis and refractory ascites.

Procedure:
• Large Volume Paracentesis
Insertion of a needle into the peritoneal cavity where ascites accumulates, then attaching the needle to a collection system that drains the ascites by gravity. This procedure is part of the standard care for the treatment of refractory ascites.

Biological:
• 25% Human Serum Albumin injection
Patients will be given Human Serum Albumin after the initial drain of ascites fluid: 100cc for 5-10L drainage, 200cc for 10-15L drainage.

Procedure:
• Bloodwork
Monthly bloodwork will be done as part of usual standard of care.

Locations

Country	Name	City	State
Canada	Health Sciences Centre	Winnipeg	Manitoba

Sponsors (1)

Lead Sponsor	Collaborator
University of Manitoba

Country where clinical trial is conducted

Canada, 

References & Publications (15)

Barnett TD, Rubins J. Placement of a permanent tunneled peritoneal drainage catheter for palliation of malignant ascites: a simplified percutaneous approach. J Vasc Interv Radiol. 2002 Apr;13(4):379-83. — View Citation

Belfort MA, Stevens PJ, DeHaek K, Soeters R, Krige JE. A new approach to the management of malignant ascites; a permanently implanted abdominal drain. Eur J Surg Oncol. 1990 Feb;16(1):47-53. — View Citation

Fleming ND, Alvarez-Secord A, Von Gruenigen V, Miller MJ, Abernethy AP. Indwelling catheters for the management of refractory malignant ascites: a systematic literature overview and retrospective chart review. J Pain Symptom Manage. 2009 Sep;38(3):341-9. doi: 10.1016/j.jpainsymman.2008.09.008. Epub 2009 Mar 28. Review. — View Citation

Lungren MP, Kim CY, Stewart JK, Smith TP, Miller MJ. Tunneled peritoneal drainage catheter placement for refractory ascites: single-center experience in 188 patients. J Vasc Interv Radiol. 2013 Sep;24(9):1303-8. doi: 10.1016/j.jvir.2013.05.042. Epub 2013 Jul 19. — View Citation

Monsky WL, Yoneda KY, MacMillan J, Deutsch LS, Dong P, Hourigan H, Schwartz Y, Magee S, Duffield C, Boak T, Cernilia J. Peritoneal and pleural ports for management of refractory ascites and pleural effusions: assessment of impact on patient quality of life and hospice/home nursing care. J Palliat Med. 2009 Sep;12(9):811-7. doi: 10.1089/jpm.2009.0061. — View Citation

Nessim SJ, Bargman JM, Jassal SV, Oliver MJ, Na Y, Perl J. The impact of transfer from hemodialysis on peritoneal dialysis technique survival. Perit Dial Int. 2015 May-Jun;35(3):297-305. doi: 10.3747/pdi.2013.00147. Epub 2013 Dec 1. — View Citation

Peltekian KM, Wong F, Liu PP, Logan AG, Sherman M, Blendis LM. Cardiovascular, renal, and neurohumoral responses to single large-volume paracentesis in patients with cirrhosis and diuretic-resistant ascites. Am J Gastroenterol. 1997 Mar;92(3):394-9. — View Citation

Planas R, Montoliu S, Ballesté B, Rivera M, Miquel M, Masnou H, Galeras JA, Giménez MD, Santos J, Cirera I, Morillas RM, Coll S, Solà R. Natural history of patients hospitalized for management of cirrhotic ascites. Clin Gastroenterol Hepatol. 2006 Nov;4(11):1385-94. — View Citation

Runyon BA; AASLD Practice Guidelines Committee. Management of adult patients with ascites due to cirrhosis: an update. Hepatology. 2009 Jun;49(6):2087-107. doi: 10.1002/hep.22853. — View Citation

Savin MA, Kirsch MJ, Romano WJ, Wang SK, Arpasi PJ, Mazon CD. Peritoneal ports for treatment of intractable ascites. J Vasc Interv Radiol. 2005 Mar;16(3):363-8. — View Citation

Senousy BE, Draganov PV. Evaluation and management of patients with refractory ascites. World J Gastroenterol. 2009 Jan 7;15(1):67-80. Review. — View Citation

Singhal S, Baikati KK, Jabbour II, Anand S. Management of refractory ascites. Am J Ther. 2012 Mar;19(2):121-32. doi: 10.1097/MJT.0b013e3181ff7a8b. Review. — View Citation

Tapping CR, Ling L, Razack A. PleurX drain use in the management of malignant ascites: safety, complications, long-term patency and factors predictive of success. Br J Radiol. 2012 May;85(1013):623-8. doi: 10.1259/bjr/24538524. Epub 2011 Mar 22. — View Citation

Van Thiel DH, Moore CM, Garcia M, George M, Nadir A. Continuous peritoneal drainage of large-volume ascites. Dig Dis Sci. 2011 Sep;56(9):2723-7. doi: 10.1007/s10620-011-1792-x. Epub 2011 Jul 7. — View Citation

Wong F. Management of ascites in cirrhosis. J Gastroenterol Hepatol. 2012 Jan;27(1):11-20. doi: 10.1111/j.1440-1746.2011.06925.x. Review. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the physical component of Quality of Life	Change in the physical component summary score of the SF 36 questionnaire.	2 months post intervention
Secondary	Catheter Insertion Technical Success Rate	Technical success rate of tunneled PD catheters: Defined as successful positioning of the catheter in the intraperitoneal space with initial drainage of ascites	Day of insertion of PD catheter
Secondary	PD Catheter Survival	Defined as days from insertion to date of a PD catheter related complication if they occur, assessed during the study timeframe.	Number of days between catheter insertion and possible complication, up to 6 months
Secondary	PD Catheter Related Complications Frequency	The number of participants with following complications: 1) Infection at the exit site or tunnel (as defined by the International Society of peritoneal Dialysis 2010 guidelines). 2) Peritonitis 3) intra-luminal/extra-luminal obstruction 4) catheter mal positioning (migration, omental wrapping) 5) Catheter leakage	through study completion, up to 6 months
Secondary	Large Volume Paracentesis Complications Frequency	The number of participants with following complications: 1) Peritonitis 2) leakage at puncture site 3) visceral puncture	through study completion, up to 6 months
Secondary	Participant Self-Reported Health Status	Measured by the number of points as a result of participants' answers to SF-36 questionnaire	0,2,4 and 6 months
Secondary	Participant Health State Description and Evaluation	Measured by the number of points as a result of participants' answers to EQ-5D questionnaire	0,2,4 and 6 months
Secondary	The Impact of Ascites on Health Related Quality of Life	Measured by the number of points as a result of participants' answers to Newcastle Patient Reported Ascites Measure questionnaire	0,2,4 and 6 months
Secondary	Renal Dysfunction Assessment	Measured by blood work: serum creatinine, serum sodium, potassium, chloride, bicarbonate, urea, glucose, eGFR (estimated glomerular filtration rate).	Monthly, up to 6 months
Secondary	Renal Function Assessment	Measured by 24 hour urine collection: creatinine clearance, urine volume and urine sodium.	at 0 and 6 months
Secondary	Serum Albumin and PD Fluid Albumin Assesment	PD catheter arm: Assessment of serum albumin and measurement of albumin in PD fluid at 0, 2, and 6 months	At 0, 2, and 6 months
Secondary	Patient Heart Rate	Patient heart rate taken as part of regular physical assessment	At regular clinic appointments, through study completion, up to 6 months
Secondary	Patient Blood Pressure	Patient blood pressure taken as part of regular physical assessment	At regular clinic appointments, through study completion, up to 6 months
Secondary	Patient Weight	Patient weight taken as part of regular physical assessment	At regular clinic appointments, through study completion, up to 6 months
Secondary	Hospital Visits	The number of hospital admissions or emergency department visits from complications related to cirrhosis (encephalopathy, gastrointestinal bleed) or peritonitis.	through study completion, up to 6 months
Secondary	Total Health Care Costs	Direct health care costs will be estimated for both groups of patients taking a health care payor perspective.	through study completion, up to 6 months
Secondary	Cost Effectiveness	A decision analysis, Markov model will be constructed between the two intervention arms with outcomes expressed as cost per quality adjusted live year (cost per QALY) and expressed as incremental cost effectiveness ratios (ICER's).	through study completion, up to 6 months