Laparoscopic Peritoneal Lavage or Resection for Generalised Peritonitis for Perforated Diverticulitis

Perforated Diverticulitis Clinical Trial

— Ladies  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01317485
• Other study ID #: NTR2037
• Status: Recruiting
• Phase: Phase 3
• First received: March 16, 2011
• Last updated: March 20, 2014
• Start date: April 2010
• Est. completion date: March 2017

Study information

• Verified date: March 2014
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: W.A. Bemelman, Professor
• Email: w.a.bemelman[@]amc.uva.nl
• Is FDA regulated: No
• Health authority: Netherlands: Dutch Health Care InspectorateNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Netherlands: ZonMw, Netherlands Organisation for Health Research and DevelopmentNetherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 283
• Est. completion date: March 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diverticulitis
• Perforated Diverticulitis
• Peritonitis

Intervention

Procedure:
• Laparoscopic lavage and drainage
[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
• Sigmoidectomy with primary anastomosis
[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.
• Sigmoidectomy with end-colostomy
[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.

Locations

Country	Name	City	State
Belgium	University Clinic St. Luc	Brussels
Belgium	University Hospital Leuven	Leuven
Netherlands	Jeroen Bosch Hospital	's-Hertogenbosch
Netherlands	Flevo Hospital	Almere
Netherlands	Rijnland Hospital	Alphen aan de Rijn and Leiderdorp
Netherlands	Meander Medical Centre	Amersfoort
Netherlands	Academic Medical Centre	Amsterdam
Netherlands	Free University Medical Centre	Amsterdam
Netherlands	Onze Lieve Vrouwe Hospital	Amsterdam
Netherlands	Slotervaart Hospital	Amsterdam
Netherlands	St. Lucas Andreas Hospital	Amsterdam
Netherlands	Alysis Medical Centre	Arnhem
Netherlands	Rode Kruis Hospital	Beverwijk
Netherlands	Amphia Hospital	Breda
Netherlands	IJsselland Hospital	Capelle aan de IJssel
Netherlands	Reinier de Graaf Hospital	Delft
Netherlands	Deventer Hospital	Deventer
Netherlands	Albert Schweitzer Hospital	Dordrecht and Zwijndrecht
Netherlands	Gelderse Vallei Hospital	Ede
Netherlands	Catharina Hospital	Eindhoven
Netherlands	Medical Spectrum Twente	Enschede
Netherlands	Groene Hart Hospital	Gouda
Netherlands	Kennemer Hospital	Haarlem
Netherlands	Atrium Medical Centre	Heerlen and Brunssum
Netherlands	Tergooi Hospitals	Hilversum and Blaricum
Netherlands	Spaarne Hospital	Hoofddorp
Netherlands	Westfries Hospital	Hoorn
Netherlands	Leiden University Medical Centre	Leiden
Netherlands	Maastricht University Medical Centre	Maastricht
Netherlands	St. Antonius Hospital	Nieuwegein
Netherlands	Erasmus Medical Centre	Rotterdam
Netherlands	Ikazia Hospital	Rotterdam
Netherlands	Maasstad Hospital	Rotterdam
Netherlands	St. Franciscus Hospital	Rotterdam
Netherlands	Orbis Medical Centre	Sittard
Netherlands	Haga Hospital	The Hague
Netherlands	Twee Steden Hospital	Tilburg and Waalwijk
Netherlands	University Medical Centre Utrecht	Utrecht
Netherlands	Máxima Medical Centre	Veldhoven
Netherlands	Zaans Medical Centre	Zaandam
Netherlands	Isala Hospitals	Zwolle

Sponsors (2)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	ZonMw: The Netherlands Organisation for Health Research and Development

Countries where clinical trial is conducted

Belgium,  Netherlands, 

References & Publications (3)

Constantinides VA, Tekkis PP, Athanasiou T, Aziz O, Purkayastha S, Remzi FH, Fazio VW, Aydin N, Darzi A, Senapati A. Primary resection with anastomosis vs. Hartmann's procedure in nonelective surgery for acute colonic diverticulitis: a systematic review. Dis Colon Rectum. 2006 Jul;49(7):966-81. Review. — View Citation

Salem L, Flum DR. Primary anastomosis or Hartmann's procedure for patients with diverticular peritonitis? A systematic review. Dis Colon Rectum. 2004 Nov;47(11):1953-64. Review. — View Citation

Toorenvliet BR, Swank H, Schoones JW, Hamming JF, Bemelman WA. Laparoscopic peritoneal lavage for perforated colonic diverticulitis: a systematic review. Colorectal Dis. 2010 Sep;12(9):862-7. doi: 10.1111/j.1463-1318.2009.02052.x. Epub 2009 Sep 26. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Secondary	Operating time		- (day 1)	No
Secondary	Hospital stay		- (day one until discharge from hospital)	No
Secondary	Number of days alive and outside the hospital		One year	No
Secondary	Incisional hernia		One year	Yes
Secondary	Reinterventions	All reinterventions within a one year time frame, including percutaneous abscess drainage.	One year	Yes
Secondary	Health related quality of life	SF-36, EQ-5D, GIQLI measured at 2, 4, 13 and 26 weeks after primary surgery.	One year	No
Secondary	Health care utilisation and associated costs	SF-HLQ measured at 4, 13, 26, 39 and 52 weeks after primary surgery	One year	No

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