search
Back to results

Self-expandable Esophageal Stent Versus Balloon Tamponade in Refractory Esophageal Variceal Bleeding.

Primary Purpose

Esophageal Varices, Bleeding, Cirrhosis

Status
Completed
Phase
Phase 3
Locations
Spain
Study Type
Interventional
Intervention
Stent
Tamponade
Sponsored by
Hospital Clinic of Barcelona
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Varices focused on measuring Acute variceal bleeding, Massive bleeding, Liver Cirrhosis, Esophageal tamponade, Esophageal stent

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

The study will include all patients with cirrhosis admitted to the hospital because an acute esophageal variceal bleeding defined according to Baveno II criteria (5) and who will achieve the following criteria:

  • Failure to control bleeding despite pharmacological (somatostatin 3 or 6 mg/12h iv or terlipressin, 2mg/4h iv) AND endoscopic therapy (esophageal banding ligation preferably or sclerotherapy). Failure to control bleeding was defined, according to Baveno IV criteria (6), as evidence of continuous digestive bleeding and any of the following:

    • Hematemesis (or naso-gastric aspirate > 100 ml of fresh blood) > 2h after the start of combined pharmacological and endoscopic therapy.
    • Decrease in hemoglobin values > 3g vs previous values (without blood transfusion).
  • Massive bleeding. Acute variceal bleeding uncontrolled despite pharmacological therapy started at any moment, with no need of previous endoscopic therapy. Uncontrolled bleeding is defined as an upper digestive bleeding in which no hemodynamic stability (systolic arterial pressure > 70 mmHg and heart rate < 100 bpm) could be achieved.

Exclusion Criteria:

  • Age < 18 years.
  • Esophageal rupture.
  • Esophageal, gastric or upper respiratory tract tumor.
  • Esophageal stenosis.
  • Recent esophageal surgery.
  • Previous esophageal tamponade to treat the index bleed.
  • Big hiatal hernia precluding the correct placement of the esophageal devices.
  • Known hepatocellular carcinoma surpassing Milan criteria.
  • Terminal disease.
  • No written consent to participate in the study.

Sites / Locations

  • Hospital Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Self-expandable esophageal stent

Sengstaken-Blakemore tube

Arm Description

The patient will receive a self-expandable esophageal stent (SX-Ella-Danis) without endoscopical guidance but under slight sedation. An immediate X-ray will be done to assess the correct placement of the stent. After a maximum of 7 days, the stent will be removed by using the specifically designed devices.

The esophageal tamponade will be done as described elsewhere. The gastric content will be checked hourly and the correct placement of the tube will be checked by an immediate X-ray. The esophageal balloon will be inflated a maximum of 24 hours.

Outcomes

Primary Outcome Measures

Combined: bleeding + absence of severe adverse events + survival
The primary endpoint combines absence of bleeding + absence of severe adverse events probably related to the study devices + survival during the first 15 days after inclusion in the study or at hospital discharge. Patients to compare are those with liver cirrhosis and acute variceal bleeding (AVB) not controlled with combined pharmacological and endoscopic therapy (see definitions). Those patients will be randomized to receive a self-expandable esophageal stent (SX-Ella-Danis) or balloon tamponade with a Sengstaken-Blakemore tube.

Secondary Outcome Measures

Bleeding
• Absence of bleeding at day 15th, 42nd and at 6 months from inclusion.
Survival
• Survival at day 15th, 42nd and at 6 months from inclusion.
Transfusional requirements
• Transfusional requirements (packed red cells, platelets and fresh frozen plasma).
Adverse events
• Individual adverse events.
Analgesia and sedation requirements
• Analgesia and sedation requirements
Hospital stay
• Hospital stay
Applicability of definitive hemostatic therapy.
• Applicability of definitive hemostatic therapy.

Full Information

First Posted
August 4, 2010
Last Updated
February 4, 2015
Sponsor
Hospital Clinic of Barcelona
Collaborators
Germans Trias i Pujol Hospital, Hospital Universitario Ramon y Cajal, Puerta de Hierro University Hospital, Hospital General Universitario Gregorio Marañon, Hospital Universitario Central de Asturias
search

1. Study Identification

Unique Protocol Identification Number
NCT01242280
Brief Title
Self-expandable Esophageal Stent Versus Balloon Tamponade in Refractory Esophageal Variceal Bleeding.
Official Title
Esophageal Stent is More Effective Than Tamponade Controlling Refractory Esophageal Variceal Bleeding: a Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
February 2015
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
June 2014 (Actual)
Study Completion Date
June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hospital Clinic of Barcelona
Collaborators
Germans Trias i Pujol Hospital, Hospital Universitario Ramon y Cajal, Puerta de Hierro University Hospital, Hospital General Universitario Gregorio Marañon, Hospital Universitario Central de Asturias

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
In the last years, important advances have been done in the treatment and prevention of esophageal variceal bleeding. Experts agree that the combination of pharmacological and endoscopic therapy should be the first line therapy in the acute bleeding episode; whereas TIPS (transjugular intrahepatic portosystemic shunt) is considered a rescue therapy. Nevertheless, some patients would require different therapies to act as a "bridge" until definitive therapy can be instituted. Balloon tamponade (using the Sengstaken tube) represents, up to now, the most widely used temporary "bridge" to TIPS. However, balloon tamponade is associated with a high incidence of serious adverse events. Recently, the use of self-expanding metal stents have been introduced in the treatment of acute variceal bleeding showing a very high hemostatic efficacy with no adverse events. The present study is directed to compare the efficacy free of adverse events and mortality of self-expanding metal stents vs balloon tamponade in patients with variceal bleeding refractory to medical and endoscopic therapy.
Detailed Description
BACKGROUND Acute variceal bleeding (AVB) carries a 20% death rate during the acute episode and nearly 50% related-mortality during the first year after the episode. (1). Prognostic factors of AVB include: the severity of bleeding, the degree of liver failure and the development of complications other than bleeding. Therefore, AVB therapy must: achieve primary hemostasis and prevent and treat both hypovolemia and related complications. After hemodynamic stabilization, upper endoscopy should be done to confirm the diagnosis and start specific therapy, that is to say: 1/ vasoactive drugs (terlipressin or somatostatin); and 2/ endoscopic therapy (variceal banding ligation). These two combined therapies achieve control of AVB in 80% of the cases (2). Nevertheless, in the remaining 20%, the AVB is not controlled requiring balloon-tamponade as a bridge to definitive hemostatic therapies such as TIPS or surgical shunts(3). The Sengstaken-Blakemore tube is the most widely used balloon tamponade. In experienced hands it provides bleeding control rates up to 90%. It should only be used by skilled staff in intensive care facilities because fatal complications may arise in more than 20% of cases. The main complications are: aspiration pneumonia, esophageal rupture, asphyxia due to balloon migration, esophageal ulcers, tongue or nose or lips necrosis, arrythmia and chest pain. These complications are time-related, therefore, balloon tamponade never must remain inflated more than 24h. Recently, a self-expandable esophageal stent has been introduced as an alternative to esophageal balloon tamponade in AVB (4). Twenty patients with AVB not controlled with combined endoscopic and pharmacological therapy were retrospectively included in the study. The patients received a self-expandable metal esophageal stent (SX-Ella-Danis, Czesc Republic). The stent was placed without complications in all cases achieving a 100% success in the control of AVB. Two to 14 days after, the stents were retired. The authors observed no case of severe stent-related complications and no rebleeding episodes (4). These data suggest that self-expandable esophageal stent could represent a safe and effective option to temporary treat patients with AVB refractory to medical and endoscopic therapy. In addition, and theoretically, esophageal stent could be associated with a lower incidence of adverse events than balloon tamponade. EXPECTED RESULTS The initial hypothesis are: The use of esophageal stents in AVB refractory to medical and endoscopic therapy is associated with a higher efficacy in absence of adverse events than balloon tamponade using the Sengstaken-Blakemore tube. The two hemostatic methods are correctly positioned in more than 90-95% of the cases. Patient's tolerability (absence of chest pain, dysphagia or food intolerance) increases with the use of esophageal stents. The applicability of definitive hemostatic therapy, such as TIPS or combined pharmacological and endoscopic eradicative therapy or surgical shunts, is higher with the use of esophageal stents that with that of the Sengstaken tube. ENDPOINTS Primary endpoint: The primary endpoint combines absence of bleeding + absence of severe adverse events probably related to the study devices + survival during the first 15 days after inclusion in the study or at hospital discharge. Patients to compare are those with liver cirrhosis and AVB not controlled with combined pharmacological and endoscopic therapy (see definitions). Those patients will be randomized to receive a self-expandable esophageal stent (SX-Ella-Danis) or balloon tamponade with a Sengstaken-Blakemore tube. Secondary endpoints: Absence of bleeding at day 15th, 42nd and at 6 months from inclusion. Survival at day 15th, 42nd and at 6 months from inclusion. Transfusional requirements (packed red cells, platelets and fresh frozen plasma). Individual adverse events. Analgesia and sedation requirements. Hospital stay. Applicability of definitive hemostatic therapy. Use of hospital resources (TIPS, derivative surgery or additional endoscopic therapy). SAMPLE SIZE The studies used to calculate the sample size are shown as references 7 to 22. None of these studies has considered a combined end-point such as in the current study. As shown, the incidence of adverse events varied over time, the highest incidence being observed in the most recent studies. In summary, we have considered that 55% of the patients receiving esophageal balloon tamponade will achieve our primary end-point. To increase this figure to 90% in the group receiving esophageal prothesis, with an 0.05 alpha error and a 0.20 beta error, the study must include 46 patients (23 per arm). STATISTICAL ANALYSIS The results will be analyzed on an intention-to-treat basis. The data will be compared by using Student t test or Chi-squared as needed. Probability and survival curves will be constructed by using the Kaplan-Meier method and compared by the Mantel-Cox test. Logistic regression will be used to identify independent predictors of survival. An interim analysis was planned after the inclusion of 28 patients (60% of the overall size). The study will be finished if the interim analysis shows significant statistical differences (p<0.02) or futility (lack of differences).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Varices, Bleeding, Cirrhosis
Keywords
Acute variceal bleeding, Massive bleeding, Liver Cirrhosis, Esophageal tamponade, Esophageal stent

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Self-expandable esophageal stent
Arm Type
Active Comparator
Arm Description
The patient will receive a self-expandable esophageal stent (SX-Ella-Danis) without endoscopical guidance but under slight sedation. An immediate X-ray will be done to assess the correct placement of the stent. After a maximum of 7 days, the stent will be removed by using the specifically designed devices.
Arm Title
Sengstaken-Blakemore tube
Arm Type
Active Comparator
Arm Description
The esophageal tamponade will be done as described elsewhere. The gastric content will be checked hourly and the correct placement of the tube will be checked by an immediate X-ray. The esophageal balloon will be inflated a maximum of 24 hours.
Intervention Type
Device
Intervention Name(s)
Stent
Intervention Description
Self-expandable esophageal stent (SX-Danis, Czesc Republic).
Intervention Type
Device
Intervention Name(s)
Tamponade
Intervention Description
Sengstaken-Blakemore tube
Primary Outcome Measure Information:
Title
Combined: bleeding + absence of severe adverse events + survival
Description
The primary endpoint combines absence of bleeding + absence of severe adverse events probably related to the study devices + survival during the first 15 days after inclusion in the study or at hospital discharge. Patients to compare are those with liver cirrhosis and acute variceal bleeding (AVB) not controlled with combined pharmacological and endoscopic therapy (see definitions). Those patients will be randomized to receive a self-expandable esophageal stent (SX-Ella-Danis) or balloon tamponade with a Sengstaken-Blakemore tube.
Time Frame
15 days
Secondary Outcome Measure Information:
Title
Bleeding
Description
• Absence of bleeding at day 15th, 42nd and at 6 months from inclusion.
Time Frame
6 months
Title
Survival
Description
• Survival at day 15th, 42nd and at 6 months from inclusion.
Time Frame
6 months
Title
Transfusional requirements
Description
• Transfusional requirements (packed red cells, platelets and fresh frozen plasma).
Time Frame
15 days
Title
Adverse events
Description
• Individual adverse events.
Time Frame
15 days
Title
Analgesia and sedation requirements
Description
• Analgesia and sedation requirements
Time Frame
15 days
Title
Hospital stay
Description
• Hospital stay
Time Frame
6 months
Title
Applicability of definitive hemostatic therapy.
Description
• Applicability of definitive hemostatic therapy.
Time Frame
15 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The study will include all patients with cirrhosis admitted to the hospital because an acute esophageal variceal bleeding defined according to Baveno II criteria (5) and who will achieve the following criteria: Failure to control bleeding despite pharmacological (somatostatin 3 or 6 mg/12h iv or terlipressin, 2mg/4h iv) AND endoscopic therapy (esophageal banding ligation preferably or sclerotherapy). Failure to control bleeding was defined, according to Baveno IV criteria (6), as evidence of continuous digestive bleeding and any of the following: Hematemesis (or naso-gastric aspirate > 100 ml of fresh blood) > 2h after the start of combined pharmacological and endoscopic therapy. Decrease in hemoglobin values > 3g vs previous values (without blood transfusion). Massive bleeding. Acute variceal bleeding uncontrolled despite pharmacological therapy started at any moment, with no need of previous endoscopic therapy. Uncontrolled bleeding is defined as an upper digestive bleeding in which no hemodynamic stability (systolic arterial pressure > 70 mmHg and heart rate < 100 bpm) could be achieved. Exclusion Criteria: Age < 18 years. Esophageal rupture. Esophageal, gastric or upper respiratory tract tumor. Esophageal stenosis. Recent esophageal surgery. Previous esophageal tamponade to treat the index bleed. Big hiatal hernia precluding the correct placement of the esophageal devices. Known hepatocellular carcinoma surpassing Milan criteria. Terminal disease. No written consent to participate in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Angels Escorsell, MD
Organizational Affiliation
Liver Unit. Hospital Clínic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Clinic
City
Barcelona
ZIP/Postal Code
08036
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
26600191
Citation
Escorsell A, Pavel O, Cardenas A, Morillas R, Llop E, Villanueva C, Garcia-Pagan JC, Bosch J; Variceal Bleeding Study Group. Esophageal balloon tamponade versus esophageal stent in controlling acute refractory variceal bleeding: A multicenter randomized, controlled trial. Hepatology. 2016 Jun;63(6):1957-67. doi: 10.1002/hep.28360. Epub 2016 Jan 14.
Results Reference
derived

Learn more about this trial

Self-expandable Esophageal Stent Versus Balloon Tamponade in Refractory Esophageal Variceal Bleeding.

We'll reach out to this number within 24 hrs