RCT to Determine the Efficacy of Combining Hemospray With Medical Treatment in Acute Variceal Bleeding

A Randomized Control Study to Determine the Efficacy and Safety of Combining Hemospray With Medical Standard of Care Treatment in the Management of Acute Variceal Bleeding in Cirrhotic Patients.

INTRODUCTION Acute variceal bleeding (AVB) is a severe complication of portal hypertension in patients with liver cirrhosis. The primary therapy includes the administration of vasoactive drugs, antibiotics and endoscopic therapy; preferably esophageal banding ligation (EBL) and/or cyanoacrylate injection when bleeding occurs from gastric varices.

In this context, the idea is to assess "Hemospray" (Cook Medical, Winston-Salem, NC) as an initial therapy in patients with massive bleeding as a temporary "bridge" until definitive treatment could be instituted.

The data generated from the pilot study performed between Erasme hospital, ULB and TBRI , Cairo showed that adding Hemospray as early as possible in the management steps could increase the bleeding control rate up to 95 % at 24 hours.

OBJECTIVE The primary efficacy objective of this study is to assess the efficacy of Hemospray in combination with standard of care (SOC) medical treatment compared to the efficacy of SOC in the Control Arm in patient with acute variceal bleeding in cirrhotic patient.

The primary safety objective of this study is to evaluate the safety of Hemospray when used in combination with SOC compared to SOC in the Control Arm.

1.1. Secondary:

• To evaluate the effect of timing of Hemospray treatment on the outcomes of bleeding patients
• To evaluate the adverse effects on both therapeutic regimens (SAEs and clinically significant AEs).

Study Overview

• Status: Completed
• Conditions: Variceal Hemorrhage
• Intervention / Treatment: Device: Hemospray; Drug: Octreotide; Biological: Blood transfusion; Drug: Ceftriaxone

Detailed Description

STUDY ENDPOINTS :

1.1. Primary endpoint: Hemostasis is the primary end point: which is a combined endpoint of Endoscopic hemostasis at (12-24) hours and Clinical hemostasis during (12-24) hours.

1.2. Secondary endpoints:

• Need for rescue endoscopy (Before 12h)
• Safety
• Interaction with coagulation profile
• Rebleeding at 5 days.
• Survival at 5 days
• Survival at 30 days

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1070
    • Erasme Hospital , ULB
• Egypt
  • Giza, Egypt, 12311
    • Theodor Bilharz Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject must be over 18 years of age.
• Suspected or proven acute variceal bleeding , Gastric lavage will be done for all patients at admission (Acute bleeding is confirmed on the presence of blood in stomach)
• Subjects must be willing to give written informed consent for the trial
• Known or suspected cirrhosis

Exclusion Criteria:

• Patient is: < 18 years of age
• Unable to consent
• Contraindicated to undergo endoscopy,
• Already hospitalized for another illness
• Pregnant or lactating
• Patients with altered post-surgical anatomy of the stomach
• Previously placed intrahepatic portosystemic shunt
• Patient treated by other endoscopic or surgical modalities within 30 days prior to the intended application of Hemospray

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hemospray; All subjects will be treated by medical treatment in the terms of combination of vasoactive medication, blood transfusion and Ceftriaxone PLUS Hemospray treatment within 2 hours of admission. The medical treatment will be continued till 12 hours after admission and then second endoscopy will be performed (12-24 hours after admission).	Device: Hemospray; Hemospray is a novel hemostatic powder licensed for endoscopic hemostasis of non-variceal upper gastrointestinal bleeding which has been shown to be effective in preliminary studies for the management of patients with peptic ulcer bleeding, including those on anticoagulant or antithrombotic therapy . Recently, two case reports and a pilot study reported that hemostatic powder may be useful in emergency management of variceal bleeding as a bridge towards more definitive therapy; Other Names: Hemostatic Powder; Drug: Octreotide; Octreotide will be administered to all patients at time of admission and will be continued for 24 hours • Dosage: 50 mcg bolus at admission then 25 mcg/hour; Other Names: Vasoactive drug; Biological: Blood transfusion; Blood transfusion will be administered to all patients if needed; Drug: Ceftriaxone; Ceftriaxone will be administered to all patients on daily basis; Other Names: Antibiotics
Active Comparator: Non Hemospray; All subjects will be treated by medical treatment in the terms of combination of Octreotide, blood transfusion and Ceftriaxone. The medical treatment will be continued till 12 hours after admission and then second endoscopy will be performed (12-24 hours after admission).	Drug: Octreotide; Octreotide will be administered to all patients at time of admission and will be continued for 24 hours • Dosage: 50 mcg bolus at admission then 25 mcg/hour; Other Names: Vasoactive drug; Biological: Blood transfusion; Blood transfusion will be administered to all patients if needed; Drug: Ceftriaxone; Ceftriaxone will be administered to all patients on daily basis; Other Names: Antibiotics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemostasis	which is a combined endpoint of Endoscopic hemostasis at (12-24) hours and Clinical hemostasis during (12-24) hours.	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Need for rescue endoscopy	12 hours
Survival	5 days
Survival	15 days
Survival	30 days

Collaborators and Investigators

• Sponsor: Theodor Bilharz Research Institute
• Collaborators: Université Libre de Bruxelles
• Investigators: Study Director: Jacques Deviere, PHD, Erasme Hospital , Université libre de Bruxelles

Publications and helpful links

General Publications

• Ibrahim M, El-Mikkawy A, Abdel Hamid M, Abdalla H, Lemmers A, Mostafa I, Deviere J. Early application of haemostatic powder added to standard management for oesophagogastric variceal bleeding: a randomised trial. Gut. 2019 May;68(5):844-853. doi: 10.1136/gutjnl-2017-314653. Epub 2018 May 5.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: November 30, 2016
• First Submitted That Met QC Criteria: February 19, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Actual): November 14, 2017
• Last Update Submitted That Met QC Criteria: November 9, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Anti-Infective Agents; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Coagulants; Ceftriaxone; Hemostatics; Anti-Bacterial Agents; Octreotide
• Other Study ID Numbers: Hemospray Varices RCT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: If data will be shared to other researchers , The patients personal data will be removed