Laparoscopic Peritoneal Lavage or Resection for Generalised Peritonitis for Perforated Diverticulitis

Study Overview
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Brief Summary
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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
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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).

Official Title
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Laparoscopic Peritoneal Lavage or Resection for Generalised Peritonitis for Perforated Diverticulitis: a Nationwide Multicenter Randomised Trial

Conditions
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Perforated Diverticulitis

Intervention / Treatment
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* Procedure: Laparoscopic lavage and drainage
* Procedure: Sigmoidectomy with primary anastomosis
* Procedure: Sigmoidectomy with end-colostomy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Purulent peritonitis<br>Patients with purulent peritonitis are randomised at a 2:1:1 ratio between Laparoscopic lavage and drainage Sigmoidectomy with primary anastomosis Sigmoidectomy with end-colostomy | Procedure: Laparoscopic lavage and drainage<br>* [CLOSED] The abdominal cavity is irrigated with six litres of warm saline in all four quadrants. At the end of the procedure a Douglas drain is inserted via the right lateral port. ***This part of the study was closed in 2013 on advice of the data and safety monitoring board due to safety issues<br>Procedure: Sigmoidectomy with primary anastomosis<br>* [OPEN] Sigmoidectomy is done according to the guidelines of the American Society of Colon and Rectal Surgeons. The distal transsection margin has to be on the proximal rectum, the proximal margin is determined by the absence of wall thickening due to diverticulitis. The type of anastomosis is done according to the preference of the operating surgeon. A loop ileostomy can be fashioned in order to ensure faecal deviation to the discretion of the surgeon.<br>* Other names: Sigmoid resection;Procedure: Sigmoidectomy with end-colostomy<br>* [OPEN] This is a two-stage procedure with the intention to close the colostomy in a second stage. During the primary surgery, only the perforated diseased part must be resected. There is no need of having the distal transsection line on the proximal rectum.<br>* Other names: Hartmann procedure;|
| Experimental: Fecal peritonitis or overt perforation<br>Patients with fecal peritonitis or an overt perforation are randomised between Sigmoidectomy with primary anastomosis Sigmoidectomy with end-colostomy | Procedure: Sigmoidectomy with primary anastomosis<br>* [OPEN] Sigmoidectomy is done according to the guidelines of the American Society of Colon and Rectal Surgeons. The distal transsection margin has to be on the proximal rectum, the proximal margin is determined by the absence of wall thickening due to diverticulitis. The type of anastomosis is done according to the preference of the operating surgeon. A loop ileostomy can be fashioned in order to ensure faecal deviation to the discretion of the surgeon.<br>* Other names: Sigmoid resection;Procedure: Sigmoidectomy with end-colostomy<br>* [OPEN] This is a two-stage procedure with the intention to close the colostomy in a second stage. During the primary surgery, only the perforated diseased part must be resected. There is no need of having the distal transsection line on the proximal rectum.<br>* Other names: Hartmann procedure;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality and major morbidity (combined) | 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. | One-year | 
| Stoma-free survival | Stoma-free survival one year after initial surgery, is the primary outcome for the comparison of the resectional strategies (DIVA). | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Operating time |  | - (day 1) | 
| Hospital stay |  | - (day one until discharge from hospital) | 
| Number of days alive and outside the hospital |  | One year | 
| Incisional hernia |  | One year | 
| Reinterventions | All reinterventions within a one year time frame, including percutaneous abscess drainage. | One year | 
| Health related quality of life | SF-36, EQ-5D, GIQLI measured at 2, 4, 13 and 26 weeks after primary surgery. | One year | 
| Health care utilisation and associated costs | SF-HLQ measured at 4, 13, 26, 39 and 52 weeks after primary surgery | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diverticulitis, perforation, sigmoidectomy, sigmoid resection, lavage, laparoscopic, wash-out, rinsing, hartmann, end-colostomy, primary anastomosis