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).