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Laparoscopic Peritoneal Lavage or Resection for Generalised Peritonitis for Perforated Diverticulitis

Phase 3
Conditions
Perforated Diverticulitis
Interventions
Procedure: Laparoscopic lavage and drainage
Procedure: Sigmoidectomy with primary anastomosis
Procedure: Sigmoidectomy with end-colostomy
Registration Number
NCT01317485
Lead Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Brief Summary

The first objective (LOLA) of this integrated trial is to determine whether laparoscopic lavage leads to better clinical outcomes compared to sigmoidectomy in patients with perforated diverticulitis with purulent peritonitis in terms of mortality and major morbidity. The second objective (DIVA) is to determine whether sigmoidectomy with anastomosis or sigmoidectomy with end-colostomy is the superior approach in patients with perforated diverticulitis with either purulent or faecal peritonitis in terms of stoma free survival. The study is designed as a multicenter and randomised trial.

Detailed Description

Patients diagnosed as having perforated diverticulitis with free air on plain abdominal X-ray or CT scan fulfilling the in- and exclusion criteria are randomised during laparoscopy via a central computer. In case of purulent diverticulitis patients are randomised to three arms: (a) laparoscopic lavage, (b) sigmoidectomy with colostomy or (c) sigmoidectomy with anastomosis in ratio of 2:1:1. In case of faecal peritonitis or an overt perforation of the sigmoid, the patient will be randomised 1:1 to sigmoidectomy with colostomy or sigmoidectomy with primary anastomosis.

The first primary outcome parameter consists of a combined endpoint consisting of mortality and major morbidity (LOLA). The second primary endpoint consists of stoma-free survival one year after initial surgery (DIVA). Secondary endpoints are number of days alive and outside the hospital, health related quality of life, health care utilisation and associated costs. A sample size of 132:66:66 patients per treatment arm will be able to detect a difference in the combined endpoint of serious complications and mortality from 25% in the two sigmoidectomy groups compared to 10% in the lavage group (two-side alpha of 5% and a power of 90%. In the DIVA analysis 2x132 patients are needed to significantly demonstrate a difference of 30% in stoma-free survival between both treatment arms (log rank test two-sided alpha of 5% and power of 90%) in favour of the patients with primary anastomosis. More than 35 hospitals will participate in this study with an estimated total inclusion of 100 patients per year. Patients will be followed for one year.

The study will be executed in concordance with the protocol, the Good Clinical Practice guidelines and regulatory requirements.

After closure of the LOLA-arm due to safety concerns for laparoscopic lavage, the protocol and sample size has for the DIVA-arm been adjusted to 118 patients per study arm (faecal or purulent peritonitis).

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
283
Inclusion Criteria

patients suspected of diverticulitis

  • age in between 18 and 85 years old
  • with written informed consent
  • with free air on plain abdominal or thoracic X-ray or CT-scan OR with peritonitis and diffuse gas or fluid on CT-scan
Exclusion Criteria
  • dementia
  • prior sigmoidectomy
  • steroid treatment > 20 mg daily
  • prior pelvic irradiation
  • preoperative shock: requirement of inotropics due to circulatory insufficiency

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Purulent peritonitisLaparoscopic lavage and drainagePatients with purulent peritonitis are randomised at a 2:1:1 ratio between 1. Laparoscopic lavage and drainage 2. Sigmoidectomy with primary anastomosis 3. Sigmoidectomy with end-colostomy
Purulent peritonitisSigmoidectomy with primary anastomosisPatients with purulent peritonitis are randomised at a 2:1:1 ratio between 1. Laparoscopic lavage and drainage 2. Sigmoidectomy with primary anastomosis 3. Sigmoidectomy with end-colostomy
Purulent peritonitisSigmoidectomy with end-colostomyPatients with purulent peritonitis are randomised at a 2:1:1 ratio between 1. Laparoscopic lavage and drainage 2. Sigmoidectomy with primary anastomosis 3. Sigmoidectomy with end-colostomy
Fecal peritonitis or overt perforationSigmoidectomy with primary anastomosisPatients with fecal peritonitis or an overt perforation are randomised between 1. Sigmoidectomy with primary anastomosis 2. Sigmoidectomy with end-colostomy
Fecal peritonitis or overt perforationSigmoidectomy with end-colostomyPatients with fecal peritonitis or an overt perforation are randomised between 1. Sigmoidectomy with primary anastomosis 2. Sigmoidectomy with end-colostomy
Primary Outcome Measures
NameTimeMethod
Mortality and major morbidity (combined)One-year

The primary outcome in the lavage vs. resectional intervention comparison (LOLA), will be poor clinical outcome, defined as a combined endpoint consisting of mortality and major morbidity one year after initial surgery. Major morbidity includes any of the following events or conditions: reintervention, wound dehiscence, incisional hernia, abscess needing percutaneous drainage, urosepsis, myocardial infarction, renal failure and respiratory insufficiency.

Stoma-free survivalOne year

Stoma-free survival one year after initial surgery, is the primary outcome for the comparison of the resectional strategies (DIVA).

Secondary Outcome Measures
NameTimeMethod
Operating time- (day 1)
Hospital stay- (day one until discharge from hospital)
Number of days alive and outside the hospitalOne year
Incisional herniaOne year
ReinterventionsOne year

All reinterventions within a one year time frame, including percutaneous abscess drainage.

Health related quality of lifeOne year

SF-36, EQ-5D, GIQLI measured at 2, 4, 13 and 26 weeks after primary surgery.

Health care utilisation and associated costsOne year

SF-HLQ measured at 4, 13, 26, 39 and 52 weeks after primary surgery

Trial Locations

Locations (41)

Onze Lieve Vrouwe Hospital

🇳🇱

Amsterdam, Netherlands

Alysis Medical Centre

🇳🇱

Arnhem, Netherlands

Catharina Hospital

🇳🇱

Eindhoven, Netherlands

Medical Spectrum Twente

🇳🇱

Enschede, Netherlands

Groene Hart Hospital

🇳🇱

Gouda, Netherlands

Atrium Medical Centre

🇳🇱

Heerlen and Brunssum, Netherlands

Tergooi Hospitals

🇳🇱

Hilversum and Blaricum, Netherlands

Spaarne Hospital

🇳🇱

Hoofddorp, Netherlands

Westfries Hospital

🇳🇱

Hoorn, Netherlands

Maastricht University Medical Centre

🇳🇱

Maastricht, Netherlands

Orbis Medical Centre

🇳🇱

Sittard, Netherlands

Zaans Medical Centre

🇳🇱

Zaandam, Netherlands

University Hospital Leuven

🇧🇪

Leuven, Belgium

Albert Schweitzer Hospital

🇳🇱

Dordrecht and Zwijndrecht, Netherlands

Slotervaart Hospital

🇳🇱

Amsterdam, Netherlands

Deventer Hospital

🇳🇱

Deventer, Netherlands

Gelderse Vallei Hospital

🇳🇱

Ede, Netherlands

University Clinic St. Luc

🇧🇪

Brussels, Belgium

Flevo Hospital

🇳🇱

Almere, Netherlands

Free University Medical Centre

🇳🇱

Amsterdam, Netherlands

Rijnland Hospital

🇳🇱

Alphen aan de Rijn and Leiderdorp, Netherlands

St. Lucas Andreas Hospital

🇳🇱

Amsterdam, Netherlands

Rode Kruis Hospital

🇳🇱

Beverwijk, Netherlands

Kennemer Hospital

🇳🇱

Haarlem, Netherlands

Leiden University Medical Centre

🇳🇱

Leiden, Netherlands

St. Antonius Hospital

🇳🇱

Nieuwegein, Netherlands

St. Franciscus Hospital

🇳🇱

Rotterdam, Netherlands

University Medical Centre Utrecht

🇳🇱

Utrecht, Netherlands

Erasmus Medical Centre

🇳🇱

Rotterdam, Netherlands

Maasstad Hospital

🇳🇱

Rotterdam, Netherlands

Ikazia Hospital

🇳🇱

Rotterdam, Netherlands

Jeroen Bosch Hospital

🇳🇱

's-Hertogenbosch, Netherlands

Meander Medical Centre

🇳🇱

Amersfoort, Netherlands

Academic Medical Centre

🇳🇱

Amsterdam, Netherlands

Amphia Hospital

🇳🇱

Breda, Netherlands

Reinier de Graaf Hospital

🇳🇱

Delft, Netherlands

IJsselland Hospital

🇳🇱

Capelle aan de IJssel, Netherlands

Haga Hospital

🇳🇱

The Hague, Netherlands

Twee Steden Hospital

🇳🇱

Tilburg and Waalwijk, Netherlands

Máxima Medical Centre

🇳🇱

Veldhoven, Netherlands

Isala Hospitals

🇳🇱

Zwolle, Netherlands

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