Laparoscopic Peritoneal Lavage or Resection for Generalised Peritonitis for Perforated Diverticulitis

NCT ID: NCT01317485

Last Updated: 2014-03-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

283 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-04-30

Study Completion Date

2017-03-31

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).

Conditions

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Perforated Diverticulitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Purulent peritonitis

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

Group Type EXPERIMENTAL

Laparoscopic lavage and drainage

Intervention Type PROCEDURE

\[CLOSED\] 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

Intervention Type PROCEDURE

\[OPEN\] 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

Intervention Type PROCEDURE

\[OPEN\] 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.

Fecal peritonitis or overt perforation

Patients with fecal peritonitis or an overt perforation are randomised between

1. Sigmoidectomy with primary anastomosis
2. Sigmoidectomy with end-colostomy

Group Type EXPERIMENTAL

Sigmoidectomy with primary anastomosis

Intervention Type PROCEDURE

\[OPEN\] 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

Intervention Type PROCEDURE

\[OPEN\] 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.

Interventions

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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

Intervention Type PROCEDURE

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.

Intervention Type PROCEDURE

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.

Intervention Type PROCEDURE

Other Intervention Names

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Sigmoid resection Hartmann procedure

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role collaborator

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

OTHER

Sponsor Role lead

Responsible Party

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Academic Medical Centre Amsterdam / Erasmus Medical Centre Rotterdam

Principal Investigators

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J.F. Lange, Professor

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Centre, Rotterdam

W.A. Bemelman, Professor

Role: PRINCIPAL_INVESTIGATOR

Academic Medical Centre, Amsterdam

Locations

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University Clinic St. Luc

Brussels, , Belgium

Site Status NOT_YET_RECRUITING

University Hospital Leuven

Leuven, , Belgium

Site Status RECRUITING

Jeroen Bosch Hospital

's-Hertogenbosch, , Netherlands

Site Status RECRUITING

Flevo Hospital

Almere Stad, , Netherlands

Site Status RECRUITING

Rijnland Hospital

Alphen Aan de Rijn and Leiderdorp, , Netherlands

Site Status NOT_YET_RECRUITING

Meander Medical Centre

Amersfoort, , Netherlands

Site Status RECRUITING

Academic Medical Centre

Amsterdam, , Netherlands

Site Status RECRUITING

Free University Medical Centre

Amsterdam, , Netherlands

Site Status RECRUITING

Onze Lieve Vrouwe Hospital

Amsterdam, , Netherlands

Site Status RECRUITING

Slotervaart Hospital

Amsterdam, , Netherlands

Site Status RECRUITING

St. Lucas Andreas Hospital

Amsterdam, , Netherlands

Site Status RECRUITING

Alysis Medical Centre

Arnhem, , Netherlands

Site Status RECRUITING

Rode Kruis Hospital

Beverwijk, , Netherlands

Site Status RECRUITING

Amphia Hospital

Breda, , Netherlands

Site Status RECRUITING

IJsselland Hospital

Capelle aan den IJssel, , Netherlands

Site Status RECRUITING

Reinier de Graaf Hospital

Delft, , Netherlands

Site Status RECRUITING

Deventer Hospital

Deventer, , Netherlands

Site Status NOT_YET_RECRUITING

Albert Schweitzer Hospital

Dordrecht and Zwijndrecht, , Netherlands

Site Status RECRUITING

Gelderse Vallei Hospital

Ede, , Netherlands

Site Status RECRUITING

Catharina Hospital

Eindhoven, , Netherlands

Site Status RECRUITING

Medical Spectrum Twente

Enschede, , Netherlands

Site Status RECRUITING

Groene Hart Hospital

Gouda, , Netherlands

Site Status RECRUITING

Kennemer Hospital

Haarlem, , Netherlands

Site Status RECRUITING

Atrium Medical Centre

Heerlen and Brunssum, , Netherlands

Site Status RECRUITING

Tergooi Hospitals

Hilversum and Blaricum, , Netherlands

Site Status RECRUITING

Spaarne Hospital

Hoofddorp, , Netherlands

Site Status RECRUITING

Westfries Hospital

Hoorn, , Netherlands

Site Status RECRUITING

Leiden University Medical Centre

Leiden, , Netherlands

Site Status NOT_YET_RECRUITING

Maastricht University Medical Centre

Maastricht, , Netherlands

Site Status RECRUITING

St. Antonius Hospital

Nieuwegein, , Netherlands

Site Status RECRUITING

Erasmus Medical Centre

Rotterdam, , Netherlands

Site Status RECRUITING

Ikazia Hospital

Rotterdam, , Netherlands

Site Status RECRUITING

Maasstad Hospital

Rotterdam, , Netherlands

Site Status RECRUITING

St. Franciscus Hospital

Rotterdam, , Netherlands

Site Status RECRUITING

Orbis Medical Centre

Sittard, , Netherlands

Site Status RECRUITING

Haga Hospital

The Hague, , Netherlands

Site Status RECRUITING

Twee Steden Hospital

Tilburg and Waalwijk, , Netherlands

Site Status RECRUITING

University Medical Centre Utrecht

Utrecht, , Netherlands

Site Status RECRUITING

Máxima Medical Centre

Veldhoven, , Netherlands

Site Status RECRUITING

Zaans Medical Centre

Zaandam, , Netherlands

Site Status RECRUITING

Isala Hospitals

Zwolle, , Netherlands

Site Status RECRUITING

Countries

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Belgium Netherlands

Central Contacts

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W.A. Bemelman, Professor

Role: CONTACT

J.F. Lange, Professor

Role: CONTACT

Facility Contacts

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A. Kartheuser

Role: primary

A. d'Hoore

Role: primary

H. Prins

Role: primary

M. Boom

Role: primary

P.A. Neijenhuis

Role: primary

E.C.J. Consten

Role: primary

W.A. Bemelman

Role: primary

D.L. van der Peet

Role: primary

M.F. Gerhards

Role: primary

S.C. Bruin

Role: primary

B.A. van Wagensveld

Role: primary

C.F.J.M. Blanken-Peeters

Role: primary

H.A. Cense

Role: primary

R.M.P.M. Crolla

Role: primary

E.J.R. de Graaf

Role: primary

T.M. Karsten

Role: primary

R.J.I. Bosker

Role: primary

J.A.B. van der Hoeven

Role: primary

Ph.M. Kruyt

Role: primary

S.W. Nienhuijs

Role: primary

E.B. van Duyn

Role: primary

D.J. Swank

Role: primary

H.B.A.C. Stockmann

Role: primary

M.N. Sosef

Role: primary

A.A.W. van Geloven

Role: primary

Q.A.J. Eijsbouts

Role: primary

M.J.P.M. Govaert

Role: primary

R.A.E.M. Tollenaar

Role: primary

L.P.S. Stassen

Role: primary

M.J. Wiezer

Role: primary

J.F. Lange

Role: primary

W.F. Weidema

Role: primary

P.P.L.O. Coene

Role: primary

G.H.H. Mannaerts

Role: primary

A.G.M. Hoofwijk

Role: primary

W.H. Steup

Role: primary

J.K. Maring

Role: primary

W.M.U. van Grevenstein

Role: primary

G.D. Slooter

Role: primary

A.F. Engel

Role: primary

E.G.J.M. Pierik

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 19788490 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15622591 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16752192 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35606544 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31178342 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26209030 (View on PubMed)

Related Links

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Other Identifiers

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NTR2037

Identifier Type: -

Identifier Source: org_study_id

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