- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01317485
Laparoscopic Peritoneal Lavage or Resection for Generalised Peritonitis for Perforated Diverticulitis (Ladies)
Laparoscopic Peritoneal Lavage or Resection for Generalised Peritonitis for Perforated Diverticulitis: a Nationwide Multicenter Randomised Trial
Study Overview
Status
Conditions
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).
Study Type
Enrollment (Anticipated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: W.A. Bemelman, Professor
- Email: w.a.bemelman@amc.uva.nl
Study Contact Backup
- Name: J.F. Lange, Professor
- Email: j.f.lange@erasmusmc.nl
Study Locations
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Brussels, Belgium
- Not yet recruiting
- University Clinic St. Luc
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Contact:
- A. Kartheuser
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Sub-Investigator:
- C. Remue
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Leuven, Belgium
- Recruiting
- University Hospital Leuven
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Contact:
- A. d'Hoore
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-
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's-Hertogenbosch, Netherlands
- Recruiting
- Jeroen Bosch Hospital
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Contact:
- H. Prins
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Almere, Netherlands
- Recruiting
- Flevo Hospital
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Contact:
- M. Boom
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Alphen aan de Rijn and Leiderdorp, Netherlands
- Not yet recruiting
- Rijnland Hospital
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Contact:
- P.A. Neijenhuis
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Amersfoort, Netherlands
- Recruiting
- Meander Medical Centre
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Contact:
- E.C.J. Consten
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Amsterdam, Netherlands
- Recruiting
- Academic Medical Centre
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Contact:
- W.A. Bemelman
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Amsterdam, Netherlands
- Recruiting
- Free University Medical Centre
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Contact:
- D.L. van der Peet
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Amsterdam, Netherlands
- Recruiting
- Onze Lieve Vrouwe Hospital
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Contact:
- M.F. Gerhards
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Amsterdam, Netherlands
- Recruiting
- Slotervaart Hospital
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Contact:
- S.C. Bruin
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Amsterdam, Netherlands
- Recruiting
- St. Lucas Andreas Hospital
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Contact:
- B.A. van Wagensveld
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Arnhem, Netherlands
- Recruiting
- Alysis Medical Centre
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Contact:
- C.F.J.M. Blanken-Peeters
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Beverwijk, Netherlands
- Recruiting
- Rode Kruis Hospital
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Contact:
- H.A. Cense
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Breda, Netherlands
- Recruiting
- Amphia Hospital
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Contact:
- R.M.P.M. Crolla
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Capelle aan de IJssel, Netherlands
- Recruiting
- Ijsselland Hospital
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Contact:
- E.J.R. de Graaf
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Delft, Netherlands
- Recruiting
- Reinier de Graaf Hospital
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Contact:
- T.M. Karsten
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Deventer, Netherlands
- Not yet recruiting
- Deventer Hospital
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Contact:
- R.J.I. Bosker
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Dordrecht and Zwijndrecht, Netherlands
- Recruiting
- Albert Schweitzer Hospital
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Contact:
- J.A.B. van der Hoeven
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Ede, Netherlands
- Recruiting
- Gelderse Vallei Hospital
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Contact:
- Ph.M. Kruyt
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Eindhoven, Netherlands
- Recruiting
- Catharina Hospital
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Contact:
- S.W. Nienhuijs
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Enschede, Netherlands
- Recruiting
- Medical spectrum Twente
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Contact:
- E.B. van Duyn
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Gouda, Netherlands
- Recruiting
- Groene Hart Hospital
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Contact:
- D.J. Swank
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Haarlem, Netherlands
- Recruiting
- Kennemer Hospital
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Heerlen and Brunssum, Netherlands
- Recruiting
- Atrium Medical Centre
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Contact:
- M.N. Sosef
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Hilversum and Blaricum, Netherlands
- Recruiting
- Tergooi Hospitals
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Contact:
- A.A.W. van Geloven
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Hoofddorp, Netherlands
- Recruiting
- Spaarne Hospital
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Contact:
- Q.A.J. Eijsbouts
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Hoorn, Netherlands
- Recruiting
- Westfries Hospital
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Contact:
- M.J.P.M. Govaert
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Leiden, Netherlands
- Not yet recruiting
- Leiden University Medical Centre
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Contact:
- R.A.E.M. Tollenaar
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Maastricht, Netherlands
- Recruiting
- Maastricht University Medical Centre
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Contact:
- L.P.S. Stassen
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Nieuwegein, Netherlands
- Recruiting
- St. Antonius Hospital
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Contact:
- M.J. Wiezer
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Rotterdam, Netherlands
- Recruiting
- Maasstad Hospital
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Contact:
- P.P.L.O. Coene
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Rotterdam, Netherlands
- Recruiting
- Erasmus Medical Centre
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Contact:
- J.F. Lange
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Rotterdam, Netherlands
- Recruiting
- Ikazia Hospital
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Contact:
- W.F. Weidema
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Rotterdam, Netherlands
- Recruiting
- St. Franciscus Hospital
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Contact:
- G.H.H. Mannaerts
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Sittard, Netherlands
- Recruiting
- Orbis Medical Centre
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Contact:
- A.G.M. Hoofwijk
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The Hague, Netherlands
- Recruiting
- Haga Hospital
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Contact:
- W.H. Steup
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Tilburg and Waalwijk, Netherlands
- Recruiting
- Twee Steden Hospital
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Contact:
- J.K. Maring
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Utrecht, Netherlands
- Recruiting
- University Medical Centre Utrecht
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Contact:
- W.M.U. van Grevenstein
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Veldhoven, Netherlands
- Recruiting
- Maxima Medical Centre
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Contact:
- G.D. Slooter
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Zaandam, Netherlands
- Recruiting
- Zaans Medical Centre
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Contact:
- A.F. Engel
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Zwolle, Netherlands
- Recruiting
- Isala Hospitals
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Contact:
- E.G.J.M. Pierik
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Purulent peritonitis
Patients with purulent peritonitis are randomised at a 2:1:1 ratio between
|
[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
[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.
Other Names:
[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.
Other Names:
|
Experimental: Fecal peritonitis or overt perforation
Patients with fecal peritonitis or an overt perforation are randomised between
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[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.
Other Names:
[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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mortality and major morbidity (combined)
Time Frame: One-year
|
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
Time Frame: One year
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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
Time Frame: - (day 1)
|
- (day 1)
|
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Hospital stay
Time Frame: - (day one until discharge from hospital)
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- (day one until discharge from hospital)
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Number of days alive and outside the hospital
Time Frame: One year
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One year
|
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Incisional hernia
Time Frame: One year
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One year
|
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Reinterventions
Time Frame: One year
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All reinterventions within a one year time frame, including percutaneous abscess drainage.
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One year
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Health related quality of life
Time Frame: One year
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SF-36, EQ-5D, GIQLI measured at 2, 4, 13 and 26 weeks after primary surgery.
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One year
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Health care utilisation and associated costs
Time Frame: One year
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SF-HLQ measured at 4, 13, 26, 39 and 52 weeks after primary surgery
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One year
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Collaborators and Investigators
Investigators
- Principal Investigator: J.F. Lange, Professor, Erasmus Medical Centre, Rotterdam
- Principal Investigator: W.A. Bemelman, Professor, Academic Medical Centre, Amsterdam
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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. Erratum In: Lancet. 2019 Jun 1;393(10187):2200.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- NTR2037
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