Vasoconstrictors as Alternatives to Albumin After Large-Volume Paracentesis (LVP) in Cirrhosis

Cirrhosis Clinical Trial

Official title:

Vasoconstrictors as Alternatives to Albumin After Large Volume Paracentesis in Cirrhosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00108355
• Other study ID #: CLIN-016-03F
• Status: Completed
• Phase: Phase 4
• First received: April 14, 2005
• Last updated: February 3, 2014
• Start date: December 2003
• Est. completion date: August 2012

Study information

• Verified date: February 2014
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

This clinical trial compares a combination of two drugs that constrict blood vessels (Octreotide LAR and Midodrine) to albumin after large volume paracentesis. Subjects have cirrhosis and ascites.

Description:

This prospective, placebo-controlled, randomized, clinical trial compares the effect of a combination of vasoconstrictors (octreotide plus midodrine) to albumin on the time to recurrence of ascites in patients with refractory ascites treated with large volume paracentesis. The treatment allocation ratio for the two treatment arms is 1:1 using a stratified random permuted block design. Subjects are patients 18-80 years old with cirrhosis and ascites who are stratified according to the presence or absence of renal dysfunction at the time of randomization. Measurements include blood pressure, weight, girth, abdominal ultrasound, forearm blood flow, plasma renin activity, angiotensin, and aldosterone, repeated during a 6 month period.

Other known NCT identifiers

• NCT00530959

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: August 2012
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Cirrhosis of any etiology

• Age 18-80 years

• Moderate to severe ascites

Exclusion Criteria:

• No or small ascites

• Severe hepatic hydrothorax

• Recent GI (gastrointestinal) hemorrhage

• Active bacterial infection

• Cardiac failure

• Organic renal disease

• Hepatocellular carcinoma

• Severe comorbidity (advanced neoplasia)

• Serum creatinine > 3 mg/dl

• Pregnancy

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ascites
• Cirrhosis
• Liver Cirrhosis

Intervention

Drug:
• Albumin
Intravenous Albumin at a dose of 8g/liter of ascitic fluid removed
• Intravenous Saline Infusion (Albumin placebo)
Intravenous saline Infusion (Albumin placebo)
• Midodrine
Midodrine oral tablet at 10 mg three times a day.
• Oral tablet (Midodrine placebo)
Oral tablet (Midodrine placebo) three times a day
• Octreotide LAR
Octreotide LAR 20 mg intramuscular injection every 30 days
• Saline injection (Octreotide LAR placebo)
Saline intramuscular injection 5 cc every 30 days.

Procedure:
• Large Volume Paracentesis
Procedure to remove large amounts (more than 5 liter) of ascitic fluid via a catheter.

Locations

Country	Name	City	State
United States	VA Connecticut Health Care System (West Haven)	West Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

References & Publications (10)

Angeli P, Volpin R, Gerunda G, Craighero R, Roner P, Merenda R, Amodio P, Sticca A, Caregaro L, Maffei-Faccioli A, Gatta A. Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide. Hepatology. 1999 Jun;29(6):1690-7. — View Citation

Appenrodt B, Wolf A, Grünhage F, Trebicka J, Schepke M, Rabe C, Lammert F, Sauerbruch T, Heller J. Prevention of paracentesis-induced circulatory dysfunction: midodrine vs albumin. A randomized pilot study. Liver Int. 2008 Aug;28(7):1019-25. doi: 10.1111/ — View Citation

Bari K, Miñano C, Shea M, Inayat IB, Hashem HJ, Gilles H, Heuman D, Garcia-Tsao G. The combination of octreotide and midodrine is not superior to albumin in preventing recurrence of ascites after large-volume paracentesis. Clin Gastroenterol Hepatol. 2012 — View Citation

Bernardi M, Caraceni P, Navickis RJ, Wilkes MM. Albumin infusion in patients undergoing large-volume paracentesis: a meta-analysis of randomized trials. Hepatology. 2012 Apr;55(4):1172-81. doi: 10.1002/hep.24786. — View Citation

Karwa R, Woodis CB. Midodrine and octreotide in treatment of cirrhosis-related hemodynamic complications. Ann Pharmacother. 2009 Apr;43(4):692-9. doi: 10.1345/aph.1L373. Epub 2009 Mar 18. Review. — View Citation

Lata J, Marecek Z, Fejfar T, Zdenek P, Bruha R, Safka V, Hulek P, Hejda V, Dolina J, Stehlík J, Tozzi I. The efficacy of terlipressin in comparison with albumin in the prevention of circulatory changes after the paracentesis of tense ascites--a randomized — View Citation

Moreau R, Asselah T, Condat B, de Kerguenec C, Pessione F, Bernard B, Poynard T, Binn M, Grangé JD, Valla D, Lebrec D. Comparison of the effect of terlipressin and albumin on arterial blood volume in patients with cirrhosis and tense ascites treated by pa — View Citation

Singh V, Dheerendra PC, Singh B, Nain CK, Chawla D, Sharma N, Bhalla A, Mahi SK. Midodrine versus albumin in the prevention of paracentesis-induced circulatory dysfunction in cirrhotics: a randomized pilot study. Am J Gastroenterol. 2008 Jun;103(6):1399-4 — View Citation

Singh V, Kumar R, Nain CK, Singh B, Sharma AK. Terlipressin versus albumin in paracentesis-induced circulatory dysfunction in cirrhosis: a randomized study. J Gastroenterol Hepatol. 2006 Jan;21(1 Pt 2):303-7. — View Citation

Tandon P, Tsuyuki RT, Mitchell L, Hoskinson M, Ma MM, Wong WW, Mason AL, Gutfreund K, Bain VG. The effect of 1 month of therapy with midodrine, octreotide-LAR and albumin in refractory ascites: a pilot study. Liver Int. 2009 Feb;29(2):169-74. doi: 10.1111 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Recurrence of Ascites.	Comparison between Albumin (Control group) and Vasoconstrictor (Treatment group)	Variable depending on the patient, average 10 days	No
Secondary	Development of Post-paracentesis Circulatory Dysfunction (PCD)	Defined as an increase in Plasma Renin Activity (PRA) by >50% from baseline to a level > 4 ng/mL/h at post-paracentesis day	6 days after paracentesis	No