Condition category
Cancer
Date applied
20/12/2005
Date assigned
20/12/2005
Last edited
18/01/2010
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr N A van der Gaag

ORCID ID

Contact details

Academic Medical Centre
Department of Surgery
Meibergdreef 9
P.O. Box 226600
Amsterdam
1100 DD
Netherlands
+31 (0)20 5662661
n.a.vandergaag@amc.uva.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

NTR234

Study information

Scientific title

Acronym

DROP-trial

Study hypothesis

Early surgical treatment (exploration followed by resection [pancreatoduodenectomy] or bypass) in patients with obstructive jaundice due to a pancreatic head tumour is equivalent in terms of severe complications of treatment compared with patients who underwent preoperative biliary drainage (four weeks) and subsequent surgery, while reducing hospital stay, the number of invasive diagnostic procedures (Endoscopic Retrograde Cholangiopancreatography [ERCP]) and results in lower overall costs.

Ethics approval

Ethics approval received from the local medical ethics committee

Study design

Randomised active controlled parallel group multicentre trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Jaundice, bile duct tumour, pancreas tumour, Papilla of Vater tumour

Intervention

Preoperative biliary drainage:
Drainage procedure will be performed within three days after randomisation for a total of four weeks.

1. ERCP and preoperative biliary drainage will be performed by an experienced endoscopist, preferably by endoscopically insertion of a (plastic) stent
2. One stent is generally sufficient because only distal obstruction is included
3. If ERCP is not successful, patient can be referred to a centre for a second attempt for endoscopic drainage or a percutaneous drainage will be performed according to local experience
4. Biliary drainage is considered adequate if a decrease of greater than 50% of serum bilirubin level is found after two weeks of drainage; otherwise the stent should be changed
5. Exactly four weeks of preoperative biliary drainage patients will undergo surgery. In case of complications after ERCP or during the biliary drainage period (cholangitis, stent occlusion) a stent exchange will be performed.
6. Other complications, such as bleeding or severe pancreatitis, should be treated according to the general locally accepted treatment protocol and/or consensus about management and could consequently lead to a delay of surgery
7. Preoperative nutritional support (e.g. consultation with a dietician, nutri-drink) is recommended in patients with a weight loss of more than 15% during the last three months

Surgical treatment:
Surgery will be performed within one week after randomisation. Guidelines for exploration and treatment are described below:

1. Surgery should be planned keeping in mind that the maximum estimated bilirubin level (greater than 40 µmol/l and less than 250 µmol/l at randomization) must not exceed 300 µmol/l, 24 hours before surgery (e.g. high bilirubin at randomization requires earlier surgery)
2. Vitamin K (10 mg, oral, one day preoperatively) is given on indication and cefuroxim (1500 mg, intravenous single shot, ½ hour preoperatively) and sandostatin (or other analogues) (three times 100 µg, subcutaneous, 12 hours before surgery and continued for seven days after surgery) as prophylaxis
3. During exploration the standard procedure will be the standard pylorus preserving pancreatoduodenectomy as previously described (removal lymph nodes right side of portal vein). If indicated (suspicious ingrowth proximal duodenum/pylorus), a whipple procedure can be performed. In case of minimal vascular ingrowth a wedge resection of the portal/mesenteric vein can be performed
4. Reconstruction is performed by pancreaticojejunostomy, a hepaticojejunostomy and gastrojejunostomy
5. One silicone drain is placed near the pancreaticojejunostomy and/or one near the hepaticojejunostomy; T-drains will not be used
6. A feeding jejunostomy is not to be used as standard treatment
7. If resection is not performed due to metastases or local ingrowth biopsies have to be taken

Palliative treatment should be performed by a hepaticojejunostomy with gastroenterostomy plus a celiac plexus blockade. If a hepaticojejunostomy is not possible a wall stent should be placed during a postoperative ERCP session.

Please note that the anticipated end date of this trial has been extended to the 1st November 2007.

Intervention type

Other

Phase

Not Specified

Drug names

Primary outcome measures

Percentage of patients with severe complications due to drainage or postoperative within 120 days after randomisation (90 days after surgery).

Secondary outcome measures

1. Hospital stay
2. Number of extra invasive diagnostic procedures
3. Costs
4. Quality of life
5. Analysis of CT criteria for resectability

Overall trial start date

01/11/2003

Overall trial end date

01/11/2006

Reason abandoned

Eligibility

Participant inclusion criteria

1. Clinical diagnosis of obstructive jaundice due to a pancreatic head or periampullary tumour
2. A serum bilirubin level of greater than 40 µmol/l and less than 250 µmol/l at randomisation
3. A spiral Computed Tomography (CT) scan according to standard protocol without metastases or local tumour ingrowth in the portal or mesenteric vessels of greater than 180°
4. Referred for surgical treatment to one of the participating centres
5. Time between CT and randomisation less than or equal to four days
6. Informed consent

Participant type

Patient

Age group

Adult

Gender

Not Specified

Target number of participants

210

Participant exclusion criteria

1. Aged greater than 85 years or severe co-morbidity (Karnofsky less than 50%) and other contra-indications for major surgery
2. Cholangitis/infection
3. Previous ERCP and stenting or percutaneous biliary drainage
4. Previous chemotherapy for this malignancy
5. Severe gastric outlet obstruction (stenosis duodenum due to tumour growth) defined as vomiting, nausea and/or oral intake less than 1 l/day

Recruitment start date

01/11/2003

Recruitment end date

01/11/2006

Locations

Countries of recruitment

Netherlands

Trial participating centre

Academic Medical Centre
Amsterdam
1100 DD
Netherlands

Sponsor information

Organisation

Academic Medical Centre (Netherlands)

Sponsor details

Meibergdreef 9
Amsterdam
1105 AZ
Netherlands

Sponsor type

University/education

Website

http://www.amc.uva.nl

Funders

Funder type

Research organisation

Funder name

The Netherlands Organisation for Health Research and Development (ZonMw) (Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2007 protocol in http://www.ncbi.nlm.nih.gov/pubmed/17352805
2. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20071702

Publication citations

  1. Results

    van der Gaag NA, Rauws EA, van Eijck CH, Bruno MJ, van der Harst E, Kubben FJ, Gerritsen JJ, Greve JW, Gerhards MF, de Hingh IH, Klinkenbijl JH, Nio CY, de Castro SM, Busch OR, van Gulik TM, Bossuyt PM, Gouma DJ, Preoperative biliary drainage for cancer of the head of the pancreas., N. Engl. J. Med., 2010, 362, 2, 129-137, doi: 10.1056/NEJMoa0903230.

  2. van der Gaag NA, de Castro SM, Rauws EA, Bruno MJ, van Eijck CH, Kuipers EJ, Gerritsen JJ, Rutten JP, Greve JW, Hesselink EJ, Klinkenbijl JH, Rinkes IH, Boerma D, Bonsing BA, van Laarhoven CJ, Kubben FJ, van der Harst E, Sosef MN, Bosscha K, de Hingh IH, Th de Wit L, van Delden OM, Busch OR, van Gulik TM, Bossuyt PM, Gouma DJ, Preoperative biliary drainage for periampullary tumors causing obstructive jaundice; DRainage vs. (direct) OPeration (DROP-trial)., BMC Surg, 2007, 7, 3, doi: 10.1186/1471-2482-7-3.

Additional files

Editorial Notes