Laparoscopic Peritoneal Lavage or Resection for Generalised Peritonitis for Perforated Diverticulitis (Ladies)

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Status and phase: Unknown; Phase 3

Conditions: Perforated Diverticulitis

Treatments: Procedure: Laparoscopic lavage and drainage; Procedure: Sigmoidectomy with primary anastomosis; Procedure: Sigmoidectomy with end-colostomy

Study type: Interventional

Funder types: Other

Identifiers

NCT01317485

NTR2037

Details and patient eligibility

About

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.

Full 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).

Enrollment: 283 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

283 participants in 2 patient groups

Purulent peritonitis

Experimental group

Description:

Patients 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

Treatment:

Procedure: Sigmoidectomy with end-colostomy

Procedure: Laparoscopic lavage and drainage

Procedure: Sigmoidectomy with primary anastomosis

Fecal peritonitis or overt perforation

Experimental group

Description:

Patients with fecal peritonitis or an overt perforation are randomised between 1. Sigmoidectomy with primary anastomosis 2. Sigmoidectomy with end-colostomy

Treatment:

Procedure: Sigmoidectomy with end-colostomy

Procedure: Sigmoidectomy with primary anastomosis