Use of Sanvar® With Endoscopic Treatment for the Control of Acute Variceal Bleeding

The Early Use of Sanvar® With Endoscopic Treatment for the Control of Acute Variceal Bleeding Due to Portal Hypertension

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.

Study Overview

• Status: Completed
• Conditions: Portal Hypertension; Esophageal Varices; Gastric Varices; Esophageal Bleeding
• Intervention / Treatment: Drug: Sanvar® (vapreotide)

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.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-0005
      • UAB Liver Center
    • Montgomery, Alabama, United States, 36116
      • Alabama Liver & Digestive Specialists
  • Arizona
    • Scottsdale, Arizona, United States, 85054
      • Mayo Clinic
  • California
    • San Diego, California, United States, 92103-8707
      • University of California at San Diego
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado Health Sciences Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University, The Feinberg School of Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins Hospital & School of Medicine, Div. of Gastroenterology & Hepatology
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10021
      • Weill Medical College of Cornell University
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospitals, Inc.
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • San Antonio, Texas, United States, 78229
      • CHRISTUS Santa Rosa Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University MCV Campus West Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	5 days

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the following:
The effect of drug administration before endoscopy assessed by the endoscopic facilitation and control of bleeding at endoscopy,	Endoscopy
Control of bleeding 6 hours after infusion of the study drug (= Tinf + 6h),	Tinf + 6h
Control of bleeding by time periods (Tendo+6h, Tendo+48h and Tendo+ 120h) by Child Pugh class,	Tendo+6h, Tendo+48h and Tendo+ 120h
Number of blood units administered during the 5 days of drug infusion,	5 days
Safety of treatment	42 days

Collaborators and Investigators

• Sponsor: Debiovision
• Investigators: Principal Investigator: Arun J. Sanyal, M.D., Virginia Commonwealth University; Study Chair: Joseph Lim, M.D., Yale University; Principal Investigator: Tarek Hassanein, M.D., University of California, San Diego; Principal Investigator: Michael B. Fallon, M.D., UAB Liver Center, Division of Gastroenterology & Hepatology; Principal Investigator: Daniel R. Ganger, M.D., Northwestern Memorial Hospital; Principal Investigator: Naga P. Chalasani, M.D., Indiana University School of Medicine; Principal Investigator: Adrian Reuben, M.D., Medical University of South Carolina; Principal Investigator: Paul J. Thuluvath, M.D., The Johns Hopkins Hospital & School of Medicine; Principal Investigator: James F. Trotter, M.D., University of Colorado, Denver; Principal Investigator: Hugo Vargas, M.D., Mayo Clinic Scottsdale, Arizona; Principal Investigator: Samuel Sigal, M.D., Weill Medical College of Cornell University; Principal Investigator: Michele D. Bishop, M.D., Mayo Clinic Jacksonville Florida; Principal Investigator: Gary A. Abrams, M.D., Alabama Liver & Digestive Specialists Research Center - Montgomery, AB; Principal Investigator: Robert S. McFadden, M.D., CHRISTUS Santa Rosa Medical Center - San Antonio, TX; Principal Investigator: Nezam H. Afdhal, M.D., Beth Israel Deaconess Medical Center, Boston MA; Principal Investigator: Jeffrey S. Crippin, M.D., Washington University School of Medicine; Principal Investigator: Alvaro Koch, M.D., University of Kentucky Medical Center - Lexington, KY; Principal Investigator: Kimberly Beavers, M.D., M. Ph., Mission Hospitals, Inc. - Asheville, NC

Publications and helpful links

General Publications

• 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.

Helpful Links

• N Engl J Med. 2001 Jan 4;344(1):23-8

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: May 26, 2006
• First Submitted That Met QC Criteria: May 26, 2006
• First Posted (Estimate): May 29, 2006

Study Record Updates

• Last Update Posted (Estimate): July 8, 2008
• Last Update Submitted That Met QC Criteria: July 7, 2008
• Last Verified: July 1, 2008

More Information

Terms related to this study

• Keywords: Liver Cirrhosis; Cirrhosis; Portal Hypertension; Hepatic Cirrhosis; Esophageal Variceal Bleeding; Somatostatin Analog; Vapreotide; Acute Esophageal Variceal Bleeding
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Gastrointestinal Diseases; Liver Diseases; Esophageal Diseases; Hypertension; Hemorrhage; Esophageal and Gastric Varices; Hypertension, Portal; Varicose Veins; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Antineoplastic Agents; Vapreotide
• Other Study ID Numbers: DEBV-VAP/EVB-301