Trial document




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  DRKS00007941

Trial Description

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Title

Endoscopic Stenting versus conservative treatment of esophago-enteric anastomotic leakages

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Trial Acronym

ESOLEAK

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URL of the Trial

http://na

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Brief Summary in Lay Language

The only curative treatment option for malignant esophageal and gastric tumors is surgical removal if no metastases have occurred in other organs. One of the most common complications is a leakage of the newly created connection between the esophagus and the stomach or intestines. Due to the potentially serious complications, this is one of the most feared incidents in general surgery. Despite continuous improvements in operative and post-operative treatment, the mortality remains very high (up to 50%). The optimal treatment strategy of this complication is controversial. The spectrum of treatment options is ranging from conservative about endoscopic treatments to aggressive surgical approaches. A systematic review our group has shown that due to the lack of studies with a high level of evidence, the superiority of the lot described and performed endoscopic treatment of conservative treatment can not be proven. The data from our hospital to confirm this result.
The proposed study will investigate whether endoscopic therapy with stent-insertion is actually superior to the conservative therapy. Both are standard therapies represent this complication. The educated guess of the trial is an elevated healing or discharge rate on day 44 after surgery from 50% to 80% through the stent inlay. This results in a number of cases in total of 78 patients assigned randomly to the treatment arms. Numerous other endpoints such as mortality, incidence of complications, quality of life, treatment costs are further investigated, etc.

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Brief Summary in Scientific Language

Esophago-enteric anastomotic leakage are, due to the high rate of complications with intensive care, long hospital stay and significant mortality, one of the most feared complications of abdominal surgery. Through optimization of surgical techniques and perioperative treatmen, mortality rate has been significantly reduced in recent decades. While the treatment of insufficiency of cervically located anastomoses usually consists of a simple drainage by opening the wound, the optimal treatment strategy for the intrathoracic and abdominal leakages is controversial and shows a wide range of conservative to radical surgical treatments.

Surgical revisions, repair or new installation of the anastomosis or resection of the conduits are ususally advised only for extensive necrosis or early leaks. In recent years, non-surgical, radiological and endoscopic interventional treatment options were introduced, complaining better results with reduced mortality, each with different treatment algorithms. The evidence for these treatments is, since almost exclusive retrospective case series or case-control studies exist, and patient cohorts are heterogenous, quite low; also often iatrogenic perforations and nastomotic leakages were jointly evaluated. A review and pooled analysis of 92 studies involving approximately 1.200 patients confirmed the heterogeneity of the studies. The described managements of the leakages’ are diverse, but can be basically grouped into three approaches; conservative treatment including non-surgical drainage placement, endoscopic interventions and surgical revision. Although each treatment might have its individual indication, the latter is mainly described as a back-up therapy after failure of conservative and endoscopic therapy. Multiple endoscopic therapies are presented including closing (Fibrin glue, Clipping), covering techniques (Tube, Stent) and just recently, endosponge therapy. The pooled analysis of the data revealed no significant difference regarding postoperative mortality after conservative or endoscopic therapy (12.3% and 10.7%, respectively), but for surgical revision (31.4%, p<0.001).
Taking into account that the evidence level of the underlying studies was low and during recent decades a significant improvement in perioperative treatment has taken place, only a cautious conclusion can be drawn. Endoscopic and conservative treatments seem to be superior to reoperation regarding survival and healing of the leakage. No clear superiority of endoscopic treatment over conservative methods could be shown. Moreover, the optimal endoscopic therapy remains unclear.
An analysis of our own data, comparing the endoscopical and conservatively treated patients, no significant differences were found regarding the clinical and pathological preconditions. Due to a change in the clinic’s treatment standard in 2009, significantly fewer endoscopic interventions were performed after 2010. Despite this, no significant differences were found regarding the outcome parameters reoperation rate, ventilation time, intensive care time, hospitalization, development of symptomatic stenosis and in-hospital mortality. Multivariate analysis showed two independent prognosticators for in-hospital mortality: An incomplete surgical resection and the need for a surgical revision, while all other aspects, including initial treatment of the leakage, failed to reach significance. The analysis of our data does not support the benefits and widely accepted and performed usage of endoscopic sealing of esophago-enteric anastomotic leakages.
Since under the various endoscopic techniques, endoscopic placement of a self-expanding stent seems to be the commonly used, it is compared with the conservative approach in the present prospective randomized ESOLEAK-trial. In both groups, interventional radiologically (computed tomography or ultrasound- controlled) placed drainages in case of contained leaks and the placement of a feeding tube for enteral nutrition are applied, together with the full spectrum of medical and intensive care therapy.

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Organizational Data

  •   DRKS00007941
  •   2015/04/14
  •   [---]*
  •   yes
  •   Approved
  •   PV4905, Ethik-Kommission der Ärztekammer Hamburg
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Secondary IDs

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Health Condition or Problem studied

  •   C15 -  Malignant neoplasm of oesophagus
  •   C16 -  Malignant neoplasm of stomach
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Interventions/Observational Groups

  •   In case of an leakage of an esophago-enteric anastomosis after extended gastrectomy or esophagectomy an endoscopic placement of a self-expanding Stent (metal or plastic) over the anastomotic leakage is performed. Additionally, a feeding tube is placed and - in case of a contained leakage - a radiologically placed drainage. The complete conservative and intensive care treatment can be additionally administered.
  •   Control group, no endoscopic treatment is performed. A feeding tube is placed and - in case of a contained leakage - a radiologically placed drainage. The complete conservative and intensive care treatment can be additionally administered.
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control
  •   Treatment
  •   Parallel
  •   IIIb
  •   No
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Primary Outcome

Rate of leakage healing (radiologically or endoscopical confirmed) or hospital discharge on day 44 after primary surgery

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Secondary Outcome

1. Hospitalization 2. Rate of treatment failure 3. Rate of a need of surgical revision and its kind 4. Complications 5.Mortality 6.ICU-time 7.SOFA-Score 8.Artificial ventilation time 9.Quality of life 10.Duration of leakage therapy 11.Time until endoscopical verified healing 12.Time until perusal nutrition 13. Direct costs 14. Symptomatic stenosis rate after 1 year

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Planned
  •   2015/04/17
  •   78
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   99   Years
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Additional Inclusion Criteria

1. Histological confirmed esophageal or gastric cancer or a similar surgically treated malignancy (e.g. GIST) 2.Esophagectomy or gastrectomy with an intrathiracic or intraabdominal esophago-enteric anastomosis 3.Radiologically or endoscopically verified leakage 4.Clinical symptoms or elevated inflammatory lab results due to the leakage 5.Age over 18 years 6.Ability to understand and willingness to consent to formal requirements for study participation 7.Written informed consent

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Exclusion Criteria

1. Macroscopical incomplete resection(R2) 2.Endoscopically verified conduit necrosis 3.Leakage size over 2/3 of circumference4.Early leakage (<48 hours after surgery) 5. Pregnant or breast-feeding women

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Addresses

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    • Universitätsklinikum Hamburg-Eppendorf
    • Martinistr. 52
    • 20246  Hamburg
    • Germany
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    • Universitätsklinikum Hamburg-Eppendorf
    • Mr.  Dr. med.  Stefan  Groth 
    • Martinistr 52
    • 20246  Hamburg
    • Germany
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    • Universitätsklinikum Hamburg-Eppendorf
    • Mr.  Dr. med.  Michael  Tachezy 
    • Martinistr 52
    • 20146  Hamburg
    • Germany
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    • Universitätsklinikum Hamburg-Eppendorf
    • Mr.  Dr. med.  Michael  Tachezy 
    • Martinistr 52
    • 20146  Hamburg
    • Germany
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Sources of Monetary or Material Support

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    • Hamburger Krebsgesellschaft e.V.
    • Butenfeld 18
    • 22528  Hamburg
    • Germany
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    • Universitätsklinikum Hamburg-EppendorfKlinik für Allgemein, Viszeral und ThoraxchiurgieKlinik für Interdisziplinäre Endoskopie
    • Martinistr 52
    • 20246  Hamburg
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.