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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
|
| 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Albumin | Drug | Intravenous Albumin at a dose of 8g/liter of ascitic fluid removed |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to Recurrence of Ascites. | Comparison between Albumin (Control group) and Vasoconstrictor (Treatment group) | Variable depending on the patient, average 10 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Guadalupe Garcia-Tsao, MD | VA Connecticut Health Care System (West Haven) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA Connecticut Health Care System (West Haven) | West Haven | Connecticut | 06516 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19299324 | Background | 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. | |
| 22095893 | Result | 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. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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) |
| FG001 | Vasoconstrictors (Study Group) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Intravenous Saline Infusion (Albumin placebo) | Drug | Intravenous saline Infusion (Albumin placebo) |
|
| Midodrine | Drug | Midodrine oral tablet at 10 mg three times a day. |
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| Oral tablet (Midodrine placebo) | Drug | Oral tablet (Midodrine placebo) three times a day |
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| Octreotide LAR | Drug | Octreotide LAR 20 mg intramuscular injection every 30 days |
|
| Saline injection (Octreotide LAR placebo) | Drug | Saline intramuscular injection 5 cc every 30 days. |
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| Large Volume Paracentesis | Procedure | Procedure to remove large amounts (more than 5 liter) of ascitic fluid via a catheter. |
|
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| 11772973 | 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. |
| 18251131 | 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. |
| 10347109 | 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. |
| 22801062 | 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. |
| 18410283 | 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. |
| 18547224 | 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. |
| 18492024 | 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. |
| 16460491 | 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. |
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 |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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) |
| BG001 | Vasoconstrictor (Treatment 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 |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Median | Inter-Quartile Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Time to Recurrence of Ascites. | Comparison between Albumin (Control group) and Vasoconstrictor (Treatment group) | Posted | Median | Inter-Quartile Range | days | Variable depending on the patient, average 10 days |
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| 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 | 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. | Posted | Number | participants | 6 days after paracentesis |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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) | 0 | 13 | 3 | 13 | ||
| EG001 | Vasoconstrictor (Treatment 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 | 0 | 12 | 4 | 12 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders |
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| GI Bleeding | Gastrointestinal disorders |
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| Hepatic encephalopathy | Hepatobiliary disorders |
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| Scrotal edema | Renal and urinary disorders |
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| Pruritis | Skin and subcutaneous tissue disorders |
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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.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Guadalupe Garcia-Tsao | VA-CT Healthcare System | 203-932-5711 | 2210 | guadalupe.garcia-tsao@yale.edu |
| ID | Term |
|---|---|
| D001201 | Ascites |
| D005355 | Fibrosis |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000418 | Albumins |
| D008879 | Midodrine |
| D013607 | Tablets |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
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| >=65 years |
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| Male |
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