Clinical trial NCT00331188: Use of Sanvar® With Endoscopic Treatment for the Control of Acute Variceal Bleeding
Official title: The Early Use of Sanvar® With Endoscopic Treatment for the Control of Acute Variceal Bleeding Due to Portal Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Esophageal Varices
Portal Hypertension
Gastric Varices
Esophageal Bleeding
Keywords: Esophageal Variceal Bleeding
Portal Hypertension
Hepatic Cirrhosis
Cirrhosis
Liver Cirrhosis
Somatostatin Analog
Vapreotide
Acute Esophageal Variceal Bleeding
Lead sponsor: Debiovision
Sponsor class: INDUSTRY
First posted: 2006-05-29
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main objective of this study is to determine the efficacy of early administration of Sanvar® in combination with endoscopic treatment for the control of acute variceal bleeding.

Detailed description: This is a single-arm open-label clinical study with historical controls using Sanvar® (vapreotide) administered for 5 days in patients with acute variceal bleeding due to portal hypertension.

Cirrhotic patients with a history of acute hematemesis and/or melena admitted to the emergency unit and meeting the eligibility criteria will receive, as soon as possible after admission (within a maximum of 24 hours after onset of hemorrhage and within 6 hours after admission), Sanvar® (vapreotide acetate) 50 µg IV bolus followed by an IV continuous infusion of 50 µg/h for 5 days.

The diagnostic and therapeutic endoscopy will be performed as soon as possible after the initiation of the study drug infusion, but no more than 12 hours after the patient's admission to the study center. A final follow up will be performed on Day 42.

Patients for whom the source of bleeding is determined at endoscopy to be due to a cause other than portal hypertension (e.g. gastric ulcer) will be replaced. In addition, in such cases the study medication will be discontinued and patients will receive standard treatment according to the cause of their bleeding. These patients will be followed up for safety only.

\*Note: There is no provision in this study to have an expanded access program.

Eligibility criteria: Inclusion Criteria:

* Female or male cirrhotic patient aged 18 to 75 years.
* Hematemesis and/or melena (suspected to be caused by portal hypertension)
* Time interval \<=24 hours between onset of initial hemorrhage and initiation of study drug infusion.
* Time interval \<=6 hours between admission and initiation of study drug infusion.
* Anticipated time interval\<=12 hours between admission and end of therapeutic endoscopy.
* Unequivocal history of cirrhosis, either documented by at least one of classical clinical signs (abdominal collateral venous circulation, firm liver with a sharp lower liver edge, presence of spider naevi, and/or ascites), or by biochemical and/or Doppler-US signs.
* Written informed consent obtained by the patient or his/her relative(s)

Exclusion Criteria:

* Patient previously included in this study for a prior bleeding episode.
* Patients treated with a vasoactive drug such as octreotide, vasopressin or its analogue for the current episode of bleeding.
* Hepatic encephalopathy Grade IV.
* Balloon tamponade already positioned at admission.
* Known Child-Pugh score \>=13
* Pregnant or breast-feeding women.
* Known diffuse hepatocellular carcinoma.
* Known complete portal venous thrombosis.
* Bleeding from esophageal varices within the previous 6 weeks.
* Patient currently enrolled in another therapeutic study, and/or who participated in another clinical study, within the previous 6 weeks.
* Known allergy to somatostatin or somatostatin analogues.
* Previous porto-systemic shunt (TIPS) or orthotopic liver transplantation.
* Patient with known cancer.
* Patient with known chronic renal failure (serum creatinine \> 1.5 mg/dl).
* Severe concomitant disease judged by the Investigator as being incompatible with evaluation of treatment.

Primary outcomes:
measure: To determine the efficacy of the early administration of Sanvar® (vapreotide) in association with endoscopic treatment for the control of bleeding at 5 days, i.e. control of initial bleeding and prevention of early re-bleeding, plus survival.
timeFrame: 5 days
Secondary outcomes:
measure: To assess the following:
measure: The effect of drug administration before endoscopy assessed by the endoscopic facilitation and control of bleeding at endoscopy,
timeFrame: Endoscopy
measure: Control of bleeding 6 hours after infusion of the study drug (= Tinf + 6h),
timeFrame: Tinf + 6h
measure: Control of bleeding by time periods (Tendo+6h, Tendo+48h and Tendo+ 120h) by Child Pugh class,
timeFrame: Tendo+6h, Tendo+48h and Tendo+ 120h
measure: Number of blood units administered during the 5 days of drug infusion,
timeFrame: 5 days
measure: Safety of treatment
timeFrame: 42 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Liver Center
state: Alabama
city: Montgomery
country: United States
facility: Alabama Liver & Digestive Specialists
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: San Diego
country: United States
facility: University of California at San Diego
state: California
city: Denver
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Chicago
country: United States
facility: Northwestern University, The Feinberg School of Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Hospital & School of Medicine, Div. of Gastroenterology & Hepatology
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Asheville
country: United States
facility: Mission Hospitals, Inc.
state: North Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: San Antonio
country: United States
facility: CHRISTUS Santa Rosa Medical Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University MCV Campus West Hospital
state: Virginia
Study officials:
affiliation: Yale University
name: Joseph Lim, M.D.
role: STUDY_CHAIR
affiliation: University of California, San Diego
name: Tarek Hassanein, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: UAB Liver Center, Division of Gastroenterology & Hepatology
name: Michael B. Fallon, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern Memorial Hospital
name: Daniel R. Ganger, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University School of Medicine
name: Naga P. Chalasani, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of South Carolina
name: Adrian Reuben, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Johns Hopkins Hospital & School of Medicine
name: Paul J. Thuluvath, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado, Denver
name: James F. Trotter, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic Scottsdale, Arizona
name: Hugo Vargas, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Weill Medical College of Cornell University
name: Samuel Sigal, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic Jacksonville Florida
name: Michele D. Bishop, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Alabama Liver & Digestive Specialists Research Center - Montgomery, AB
name: Gary A. Abrams, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: CHRISTUS Santa Rosa Medical Center - San Antonio, TX
name: Robert S. McFadden, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Beth Israel Deaconess Medical Center, Boston MA
name: Nezam H. Afdhal, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Washington University School of Medicine
name: Jeffrey S. Crippin, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Kentucky Medical Center - Lexington, KY
name: Alvaro Koch, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Mission Hospitals, Inc. - Asheville, NC
name: Kimberly Beavers, M.D., M. Ph.
role: PRINCIPAL_INVESTIGATOR
affiliation: Virginia Commonwealth University
name: Arun J. Sanyal, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cales P, Masliah C, Bernard B, Garnier PP, Silvain C, Szostak-Talbodec N, Bronowicki JP, Ribard D, Botta-Fridlund D, Hillon P, Besseghir K, Lebrec D; French Club for the Study of Portal Hypertension. Early administration of vapreotide for variceal bleeding in patients with cirrhosis. N Engl J Med. 2001 Jan 4;344(1):23-8. doi: 10.1056/NEJM200101043440104.