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 measure
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 (if study stopped)
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
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
Basic results (scientific)
Publication list
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
-
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.
-
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.