Self-expandable Esophageal Stent Versus Balloon Tamponade in Refractory Esophageal Variceal Bleeding.
Information source: Hospital Clinic of Barcelona
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Esophageal Varices; Bleeding; Cirrhosis
Intervention: Stent (Device); Tamponade (Device)
Phase: Phase 3
Status: Completed
Sponsored by: Hospital Clinic of Barcelona Official(s) and/or principal investigator(s): Angels Escorsell, MD, Principal Investigator, Affiliation: Liver Unit. Hospital ClĂnic
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.
Clinical Details
Official title: Esophageal Stent is More Effective Than Tamponade Controlling Refractory Esophageal Variceal Bleeding: a Randomized Controlled Trial
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Combined: bleeding + absence of severe adverse events + survival
Secondary outcome: BleedingSurvival Transfusional requirements Adverse events Analgesia and sedation requirements Hospital stay Applicability of definitive hemostatic 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).
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Hospital Clinic, Barcelona 08036, Spain
Additional Information
Starting date: January 2010
Last updated: February 4, 2015
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