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

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ClinicalTrials.gov Identifier: NCT00108355
Recruitment Status : Completed
First Posted : April 15, 2005
Results First Posted : March 6, 2014
Last Update Posted : March 6, 2014
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development ( US Department of Veterans Affairs )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Ascites
Cirrhosis
Interventions Drug: Albumin
Drug: Intravenous Saline Infusion (Albumin placebo)
Drug: Midodrine
Drug: Oral tablet (Midodrine placebo)
Drug: Octreotide LAR
Drug: Saline injection (Octreotide LAR placebo)
Procedure: Large Volume Paracentesis
Enrollment 29
Recruitment Details Between October 2003 and June 2010, about 200 patients with cirrhosis and ascites were screened, of which, only 29 met inclusion criteria. Twenty five patients (13 control, 12 study group) were included in the analysis.
Pre-assignment Details  
Arm/Group Title Albumin (Control Group) Vasoconstrictors (Study Group)
Hide Arm/Group Description

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)

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

Period Title: Overall Study
Started 15 [1] 14 [2]
Completed 13 12
Not Completed 2 2
Reason Not Completed
Peritonitis at index paracentesis             1             1
Loculated ascites, limiting paracentesis             1             1
[1]
Two patients met inclusion criteria not randomized, one had peritonitis , other loculated ascites.
[2]
Two patients met inclusion criteria not randomized, one had peritonitis, other loculated ascites.
Arm/Group Title Albumin (Control Group) Vasoconstrictor (Treatment Group) Total
Hide Arm/Group Description

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)

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

Total of all reporting groups
Overall Number of Baseline Participants 13 12 25
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 12 participants 25 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
11
  84.6%
10
  83.3%
21
  84.0%
>=65 years
2
  15.4%
2
  16.7%
4
  16.0%
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
age median Number Analyzed 13 participants 12 participants 25 participants
55
(51 to 61)
60
(51 to 65)
58
(51 to 63)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 12 participants 25 participants
Female
3
  23.1%
0
   0.0%
3
  12.0%
Male
10
  76.9%
12
 100.0%
22
  88.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 13 participants 12 participants 25 participants
13 12 25
1.Primary Outcome
Title Time to Recurrence of Ascites.
Hide Description Comparison between Albumin (Control group) and Vasoconstrictor (Treatment group)
Time Frame Variable depending on the patient, average 10 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Albumin (Control Group) Vasoconstrictor (Treatment Group)
Hide Arm/Group Description:

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)

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

Overall Number of Participants Analyzed 13 12
Median (Inter-Quartile Range)
Unit of Measure: days
10
(7 to 29)
8
(6 to 22)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albumin (Control Group), Vasoconstrictor (Treatment Group)
Comments Initial estimation: median time to recurrence of ascites of 38 days in the study group and 20 days in the control group in a fixed duration of 6 months (5% type-I error (2 sided) and an 80% power). However, due to low accrual and based on randomized trials using vasoconstrictors in the prevention of PCD and a study that showed that midodrine leads to a significant improvement in effective arterial blood volume, each of which had sample sizes of 24-25 patients,we decided on a sample size of 30.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
2.Secondary Outcome
Title Development of Post-paracentesis Circulatory Dysfunction (PCD)
Hide Description Defined as an increase in Plasma Renin Activity (PRA) by >50% from baseline to a level > 4 ng/mL/h at post-paracentesis day
Time Frame 6 days after paracentesis
Hide Outcome Measure Data
Hide Analysis Population Description
Plasma Renin Activity (lab value to measure PCD) was not available for 6 patients leaving 11 patients in Albumin (control group) and 8 patients in Vasoconstrictor (Treatment group) for this outcome analysis.
Arm/Group Title Albumin (Control Group) Vasoconstrictor (Treatment Group)
Hide Arm/Group Description:

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)

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

Overall Number of Participants Analyzed 11 8
Measure Type: Number
Unit of Measure: participants
2 2
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Albumin (Control Group) Vasoconstrictor (Treatment Group)
Hide Arm/Group Description

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)

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

All-Cause Mortality
Albumin (Control Group) Vasoconstrictor (Treatment Group)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Albumin (Control Group) Vasoconstrictor (Treatment Group)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/13 (0.00%)      0/12 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Albumin (Control Group) Vasoconstrictor (Treatment Group)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/13 (23.08%)      4/12 (33.33%)    
Gastrointestinal disorders     
Diarrhea  0/13 (0.00%)  0 2/12 (16.67%)  2
GI Bleeding  1/13 (7.69%)  1 0/12 (0.00%)  0
Hepatobiliary disorders     
Hepatic encephalopathy  1/13 (7.69%)  1 0/12 (0.00%)  0
Renal and urinary disorders     
Scrotal edema  1/13 (7.69%)  1 1/12 (8.33%)  1
Skin and subcutaneous tissue disorders     
Pruritis  0/13 (0.00%)  0 1/12 (8.33%)  1
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Guadalupe Garcia-Tsao
Organization: VA-CT Healthcare System
Phone: 203-932-5711 ext 2210
Publications of Results:
Responsible Party: VA Office of Research and Development ( US Department of Veterans Affairs )
ClinicalTrials.gov Identifier: NCT00108355     History of Changes
Obsolete Identifiers: NCT00530959
Other Study ID Numbers: CLIN-016-03F
First Submitted: April 14, 2005
First Posted: April 15, 2005
Results First Submitted: December 11, 2013
Results First Posted: March 6, 2014
Last Update Posted: March 6, 2014