Clinical trial NCT01317485: Laparoscopic Peritoneal Lavage or Resection for Generalised Peritonitis for Perforated Diverticulitis
Official title: Laparoscopic Peritoneal Lavage or Resection for Generalised Peritonitis for Perforated Diverticulitis: a Nationwide Multicenter Randomised Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Perforated Diverticulitis
Keywords: diverticulitis
perforation
sigmoidectomy
sigmoid resection
lavage
laparoscopic
wash-out
rinsing
hartmann
end-colostomy
primary anastomosis
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2011-03-17
Enrollment: 283
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Mortality and major morbidity (combined)
timeFrame: One-year
measure: Stoma-free survival
timeFrame: One year
Secondary outcomes:
measure: Operating time
timeFrame: - (day 1)
measure: Hospital stay
timeFrame: - (day one until discharge from hospital)
measure: Number of days alive and outside the hospital
timeFrame: One year
measure: Incisional hernia
timeFrame: One year
measure: Reinterventions
timeFrame: One year
measure: Health related quality of life
timeFrame: One year
measure: Health care utilisation and associated costs
timeFrame: One year
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: University Clinic St. Luc
city: Leuven
country: Belgium
facility: University Hospital Leuven
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Hospital
city: Almere
country: Netherlands
facility: Flevo Hospital
city: Alphen aan de Rijn and Leiderdorp
country: Netherlands
facility: Rijnland Hospital
city: Amersfoort
country: Netherlands
facility: Meander Medical Centre
city: Amsterdam
country: Netherlands
facility: Academic Medical Centre
city: Amsterdam
country: Netherlands
facility: Free University Medical Centre
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Hospital
city: Amsterdam
country: Netherlands
facility: Slotervaart Hospital
city: Amsterdam
country: Netherlands
facility: St. Lucas Andreas Hospital
city: Arnhem
country: Netherlands
facility: Alysis Medical Centre
city: Beverwijk
country: Netherlands
facility: Rode Kruis Hospital
city: Breda
country: Netherlands
facility: Amphia Hospital
city: Capelle aan de IJssel
country: Netherlands
facility: IJsselland Hospital
city: Delft
country: Netherlands
facility: Reinier de Graaf Hospital
city: Deventer
country: Netherlands
facility: Deventer Hospital
city: Dordrecht and Zwijndrecht
country: Netherlands
facility: Albert Schweitzer Hospital
city: Ede
country: Netherlands
facility: Gelderse Vallei Hospital
city: Eindhoven
country: Netherlands
facility: Catharina Hospital
city: Enschede
country: Netherlands
facility: Medical Spectrum Twente
city: Gouda
country: Netherlands
facility: Groene Hart Hospital
city: Haarlem
country: Netherlands
facility: Kennemer Hospital
city: Heerlen and Brunssum
country: Netherlands
facility: Atrium Medical Centre
city: Hilversum and Blaricum
country: Netherlands
facility: Tergooi Hospitals
city: Hoofddorp
country: Netherlands
facility: Spaarne Hospital
city: Hoorn
country: Netherlands
facility: Westfries Hospital
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Centre
city: Rotterdam
country: Netherlands
facility: Ikazia Hospital
city: Rotterdam
country: Netherlands
facility: Maasstad Hospital
city: Rotterdam
country: Netherlands
facility: St. Franciscus Hospital
city: Sittard
country: Netherlands
facility: Orbis Medical Centre
city: The Hague
country: Netherlands
facility: Haga Hospital
city: Tilburg and Waalwijk
country: Netherlands
facility: Twee Steden Hospital
city: Utrecht
country: Netherlands
facility: University Medical Centre Utrecht
city: Veldhoven
country: Netherlands
facility: Máxima Medical Centre
city: Zaandam
country: Netherlands
facility: Zaans Medical Centre
city: Zwolle
country: Netherlands
facility: Isala Hospitals
Study officials:
affiliation: Erasmus Medical Centre, Rotterdam
name: J.F. Lange, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Academic Medical Centre, Amsterdam
name: W.A. Bemelman, Professor
role: PRINCIPAL_INVESTIGATOR
References:
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.
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. doi: 10.1007/s10350-004-0701-1.
citation: 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. doi: 10.1007/s10350-006-0547-9.
citation: Hoek VT, Edomskis PP, Stark PW, Lambrichts DPV, Draaisma WA, Consten ECJ, Lange JF, Bemelman WA; LADIES trial collaborators. Laparoscopic peritoneal lavage versus sigmoidectomy for perforated diverticulitis with purulent peritonitis: three-year follow-up of the randomised LOLA trial. Surg Endosc. 2022 Oct;36(10):7764-7774. doi: 10.1007/s00464-022-09326-3. Epub 2022 May 23.
citation: Lambrichts DPV, Vennix S, Musters GD, Mulder IM, Swank HA, Hoofwijk AGM, Belgers EHJ, Stockmann HBAC, Eijsbouts QAJ, Gerhards MF, van Wagensveld BA, van Geloven AAW, Crolla RMPH, Nienhuijs SW, Govaert MJPM, di Saverio S, D'Hoore AJL, Consten ECJ, van Grevenstein WMU, Pierik REGJM, Kruyt PM, van der Hoeven JAB, Steup WH, Catena F, Konsten JLM, Vermeulen J, van Dieren S, Bemelman WA, Lange JF; LADIES trial collaborators. Hartmann's procedure versus sigmoidectomy with primary anastomosis for perforated diverticulitis with purulent or faecal peritonitis (LADIES): a multicentre, parallel-group, randomised, open-label, superiority trial. Lancet Gastroenterol Hepatol. 2019 Aug;4(8):599-610. doi: 10.1016/S2468-1253(19)30174-8. Epub 2019 Jun 6.
citation: Vennix S, Musters GD, Mulder IM, Swank HA, Consten EC, Belgers EH, van Geloven AA, Gerhards MF, Govaert MJ, van Grevenstein WM, Hoofwijk AG, Kruyt PM, Nienhuijs SW, Boermeester MA, Vermeulen J, van Dieren S, Lange JF, Bemelman WA; Ladies trial colloborators. Laparoscopic peritoneal lavage or sigmoidectomy for perforated diverticulitis with purulent peritonitis: a multicentre, parallel-group, randomised, open-label trial. Lancet. 2015 Sep 26;386(10000):1269-1277. doi: 10.1016/S0140-6736(15)61168-0. Epub 2015 Jul 22.