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

Portal Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00331188
• Other study ID #: DEBV-VAP/EVB-301
• Status: Completed
• Phase: Phase 3
• First received: May 26, 2006
• Last updated: July 7, 2008
• Start date: May 2006
• Est. completion date: July 2008

Study information

• Verified date: July 2008
• Source: Debiovision
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: July 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal Bleeding
• Esophageal Varices
• Gastric Varices
• Hemorrhage
• Hypertension
• Hypertension, Portal
• Portal Hypertension

Intervention

Drug:
• Sanvar® (vapreotide)

Locations

Country	Name	City	State
United States	Mission Hospitals, Inc.	Asheville	North Carolina
United States	Johns Hopkins Hospital & School of Medicine, Div. of Gastroenterology & Hepatology	Baltimore	Maryland
United States	UAB Liver Center	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University, The Feinberg School of Medicine	Chicago	Illinois
United States	University of Colorado Health Sciences Center	Denver	Colorado
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Mayo Clinic	Jacksonville	Florida
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	Alabama Liver & Digestive Specialists	Montgomery	Alabama
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	Virginia Commonwealth University MCV Campus West Hospital	Richmond	Virginia
United States	CHRISTUS Santa Rosa Medical Center	San Antonio	Texas
United States	University of California at San Diego	San Diego	California
United States	Mayo Clinic	Scottsdale	Arizona
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Debiovision

Country where clinical trial is conducted

United States, 

References & Publications (1)

Calès 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. — View Citation

Outcome

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

External Links

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