Vasoconstrictors as Alternatives to Albumin After Large-Volume Paracentesis (LVP) in Cirrhosis
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Albumin (Control group) 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
Intravenous Albumin at a dose of 8g/liter of ascitic fluid removed
Drug: Oral tablet (Midodrine placebo)
Oral tablet (Midodrine placebo) three times a day
Drug: 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.
Other Names:
|
| Experimental: Vasoconstrictor (Study Group) 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)
Intravenous saline Infusion (Albumin placebo)
Drug: Midodrine
Midodrine oral tablet at 10 mg three times a day.
Drug: Octreotide LAR
Octreotide LAR 20 mg intramuscular injection every 30 days
Procedure: Large Volume Paracentesis
Procedure to remove large amounts (more than 5 liter) of ascitic fluid via a catheter.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Time to Recurrence of Ascites. [Variable depending on the patient, average 10 days]
Comparison between Albumin (Control group) and Vasoconstrictor (Treatment group)
Secondary Outcome Measures
- Development of Post-paracentesis Circulatory Dysfunction (PCD) [6 days after paracentesis]
Defined as an increase in Plasma Renin Activity (PRA) by >50% from baseline to a level > 4 ng/mL/h at post-paracentesis day
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | VA Connecticut Health Care System (West Haven) | West Haven | Connecticut | United States | 06516 |
Sponsors and Collaborators
- US Department of Veterans Affairs
Investigators
- Principal Investigator: Guadalupe Garcia-Tsao, MD, VA Connecticut Health Care System (West Haven)
Study Documents (Full-Text)
None provided.More Information
Publications
- CLIN-016-03F
- NCT00530959
Study Results
Participant Flow
| 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 Detail |
| Arm/Group Title | Albumin (Control Group) | Vasoconstrictors (Study Group) |
|---|---|---|
| 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 | 14 |
| COMPLETED | 13 | 12 |
| NOT COMPLETED | 2 | 2 |
Baseline Characteristics
| Arm/Group Title | Albumin (Control Group) | Vasoconstrictor (Treatment Group) | Total |
|---|---|---|---|
| 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 Participants | 13 | 12 | 25 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
11
84.6%
|
10
83.3%
|
21
84%
|
| >=65 years |
2
15.4%
|
2
16.7%
|
4
16%
|
| Age (years) [Median (Inter-Quartile Range) ] | |||
| age median |
55
(7.5)
|
60
(8.4)
|
58
(8)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
3
23.1%
|
0
0%
|
3
12%
|
| Male |
10
76.9%
|
12
100%
|
22
88%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
13
100%
|
12
100%
|
25
100%
|
Outcome Measures
| Title | Time to Recurrence of Ascites. |
|---|---|
| Description | Comparison between Albumin (Control group) and Vasoconstrictor (Treatment group) |
| Time Frame | Variable depending on the patient, average 10 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Albumin (Control Group) | Vasoconstrictor (Treatment Group) |
|---|---|---|
| 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 |
| Measure Participants | 13 | 12 |
| Median (Inter-Quartile Range) [days] |
10
|
8
|
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 | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Development of Post-paracentesis Circulatory Dysfunction (PCD) |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|
| 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 |
| Measure Participants | 11 | 8 |
| Number [participants] |
2
15.4%
|
2
16.7%
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Albumin (Control Group) | Vasoconstrictor (Treatment Group) | ||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Albumin (Control Group) | Vasoconstrictor (Treatment Group) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/13 (0%) | 0/12 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Albumin (Control Group) | Vasoconstrictor (Treatment Group) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/13 (23.1%) | 4/12 (33.3%) | ||
| Gastrointestinal disorders | ||||
| Diarrhea | 0/13 (0%) | 0 | 2/12 (16.7%) | 2 |
| GI Bleeding | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Hepatic encephalopathy | 1/13 (7.7%) | 1 | 0/12 (0%) | 0 |
| Renal and urinary disorders | ||||
| Scrotal edema | 1/13 (7.7%) | 1 | 1/12 (8.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Pruritis | 0/13 (0%) | 0 | 1/12 (8.3%) | 1 |
Limitations/Caveats
More Information
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 |
| guadalupe.garcia-tsao@yale.edu |
- CLIN-016-03F
- NCT00530959