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

NCT00108355 | Completed Phase 4 Results DMC

• 1 other identifier: CLIN-016-03F
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Ascites; Cirrhosis

Keywords

albumin; ascites; paracentesis

Outcome Measures

Primary Outcomes (1)

• Time to Recurrence of Ascites.

  Comparison between Albumin (Control group) and Vasoconstrictor (Treatment group)

  Variable depending on the patient, average 10 days

Secondary Outcomes (1)

• Development of Post-paracentesis Circulatory Dysfunction (PCD)

  6 days after paracentesis

Study Arms (2)

Albumin (Control group)

ACTIVE COMPARATOR

After LVP, patients in this group received: Intravenous albumin (25%) at 8 g/liter of ascitic fluid removed, one time dose; Intramuscular injection of 5 cc saline (Octreotide LAR placebo), every 30 days ; Oral tablet 3 times a day (Midodrine placebo)

Drug: Albumin; Drug: Oral tablet (Midodrine placebo); Drug: Saline injection (Octreotide LAR placebo); Procedure: Large Volume Paracentesis

Vasoconstrictor (Study Group)

EXPERIMENTAL

After LVP, patients in this group received: Octreotide LAR intramuscular injection 20 mg, every 30 days; Midodrine tablet, 10 mg three times a day; Intravenous saline infusion (Albumin placebo), one time dose

Drug: Intravenous Saline Infusion (Albumin placebo); Drug: Midodrine; Drug: Octreotide LAR; Procedure: Large Volume Paracentesis

Interventions

Albumin DRUG

Intravenous Albumin at a dose of 8g/liter of ascitic fluid removed

Albumin (Control group)

Intravenous Saline Infusion (Albumin placebo) DRUG

Intravenous saline Infusion (Albumin placebo)

Vasoconstrictor (Study Group)

Midodrine DRUG

Midodrine oral tablet at 10 mg three times a day.

Vasoconstrictor (Study Group)

Oral tablet (Midodrine placebo) DRUG

Oral tablet (Midodrine placebo) three times a day

Albumin (Control group)

Octreotide LAR DRUG

Octreotide LAR 20 mg intramuscular injection every 30 days

Vasoconstrictor (Study Group)

Saline injection (Octreotide LAR placebo) DRUG

Saline intramuscular injection 5 cc every 30 days.

Albumin (Control group)

Large Volume Paracentesis PROCEDURE

Procedure to remove large amounts (more than 5 liter) of ascitic fluid via a catheter.

Also known as: LVP

Albumin (Control group); Vasoconstrictor (Study Group)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cirrhosis of any etiology
• Age 18-80 years
• Moderate to severe ascites

You may not qualify if:

• 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

Sponsors & Collaborators

• US Department of Veterans Affairs: lead

Study Sites (1)

VA Connecticut Health Care System (West Haven)

West Haven, Connecticut, 06516, United States

Location

Related Publications (10)

• 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.

  PMID: 19299324 BACKGROUND

• 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.

  PMID: 22095893 RESULT

• Moreau R, Asselah T, Condat B, de Kerguenec C, Pessione F, Bernard B, Poynard T, Binn M, Grange 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 paracentesis: a randomised pilot study. Gut. 2002 Jan;50(1):90-4. doi: 10.1136/gut.50.1.90.

  PMID: 11772973 RESULT

• Lata J, Marecek Z, Fejfar T, Zdenek P, Bruha R, Safka V, Hulek P, Hejda V, Dolina J, Stehlik 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 multicentric study. Hepatogastroenterology. 2007 Oct-Nov;54(79):1930-3.

  PMID: 18251131 RESULT

• 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. doi: 10.1002/hep.510290629.

  PMID: 10347109 RESULT

• Bari K, Minano 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 Oct;10(10):1169-75. doi: 10.1016/j.cgh.2012.06.027. Epub 2012 Jul 16.

  PMID: 22801062 RESULT

• Appenrodt B, Wolf A, Grunhage 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/j.1478-3231.2008.01734.x. Epub 2008 Apr 11.

  PMID: 18410283 RESULT

• 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):1399-405. doi: 10.1111/j.1572-0241.2008.01787.x.

  PMID: 18547224 RESULT

• 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/j.1478-3231.2008.01778.x. Epub 2008 May 19.

  PMID: 18492024 RESULT

• 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. doi: 10.1111/j.1440-1746.2006.04182.x.

  PMID: 16460491 RESULT

MeSH Terms

Conditions

Ascites; Fibrosis

Interventions

Albumins; Midodrine; Tablets; Sodium Chloride

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Proteins; Amino Acids, Peptides, and Proteins; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Dosage Forms; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Difficulty to enroll patient population lead to small sample size. Midodrine not titrated for a goal increase in mean arterial pressure. Blood tests for day 6 assessment of post paracentesis circulatory dysfunction not available for all patients.

Results Point of Contact

• Title: Guadalupe Garcia-Tsao
• Organization: VA-CT Healthcare System

guadalupe.garcia-tsao@yale.edu

203-932-5711

Study Officials

• Guadalupe Garcia-Tsao, MD

  VA Connecticut Health Care System (West Haven)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2005
• First Posted: April 15, 2005
• Study Start: December 1, 2003
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2012
• Last Updated: March 6, 2014
• Results First Posted: March 6, 2014

Record last verified: 2014-02

Locations

US (1)