|- candidate number||15537|
|- NTR Number||NTR4243|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||11-okt-2013|
|- Secondary IDs||5925 KWF cancer foundation grant|
|- Public Title||Endoscopic versus percutaneous biliary drainage
in resectable hilar cholangiocarcinoma.|
|- Scientific Title||Endoscopic versus percutaneous biliary drainage
in resectable hilar cholangiocarcinoma.|
|- ACRONYM||DRAINAGE trial|
|- hypothesis||This study is expected to identify less complications after percutaneous biliary drainage (PTBD) compared to endoscopic biliary drainage for resectable hilar cholangiocarcinoma.|
|- Healt Condition(s) or Problem(s) studied||Bile ducts, |
|- Inclusion criteria||- Diagnosis of HCCA|
- Resectable disease according to Dutch national guidelines
- Inadequate preoperative biliary drainage.
For drainage na´ve patients this is defined as serum bilirubin level ≥ 50 Ámol/l. For drainage non-na´ve patients this is defined as persistent hyperbilirubinemia (i.e., decrease <20% in bilirubin within 7 days after last drainage procedure) or inadequate drainage of the FRL (stent positioned in contra-lateral side).
|- Exclusion criteria||- Incomplete recovery from side-effects of any prior stenting attempt, including signs of active cholangitis or pancreatitis such as fever, abdominal pain, CRP > 150 mg/L. Patients recovering from an episode of cholangitis are eligibe for inclusion when they are off antibiotic therapy ≥ 5 days without|
- Any contra-indication for either EBD or PTBD
- Serious coexisting illness; Karnofsky performance score <50 (on a scale of 0 to 100)
- Any other contraindication for major surgery
- No informed consent
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||26-sep-2013|
|- planned closingdate||1-sep-2017|
|- Target number of participants||106|
|- Interventions||Percutaneous transhepatic biliary drainage (PTBD):
The coordinating radiologists from the participating centres perform or supervise all PTBD procedures. The aim of the index procedure is to selectively drain the segments of the FRL and at least 50% of the liver. The technique for PTBD involves the use of ultrasound guidance, a thin Chiba needle and a 0.014-inch guidewire to gain access to the biliary system. Antegrade cholangiography will be used to localize the site of obstruction. The guidewire is manoeuvred through the stenosis. A catheter is placed with its distal end in the duodenum for internal-external-drainage. Externally draining bile is collected during the first 48h, after which the catheter is closed in order to achieve internal drainage.
Endoscopic biliary drainage (EBD):
The coordinating gastro-enterologists at the participating centres perform or supervise all EBD procedures. The aim of the index procedure is to selectively drain the segments of the FRL and at least 50% of the liver. A sphincterotomy with blended electrosurgical current is standard part of the procedure to facilitate the insertion of multiple stents and/or brush cytology. Opacification upstream of the obstruction is intentionally restricted to segments that are aimed to drain during the procedure. Bile duct(s) unintentionally opacified upstream from the obstruction should be drained during the same procedure. Polyethylene endoprostheses are then pushed in position over the catheter. Directly after the procedure, a 100 mg Diclofenac suppository is administered to the patient for the prevention of post ERCP-pancreatitis.
Antibiotic treatment around drainage procedures:
Standard prophylactic antibiotics at the start of each drainage procedure is 2 grams Ceftriaxon i.v plus Gentamycine 5mg/kg. Antibiotic treatment must be continued in case of incomplete biliary drainage of opacified liver segments, consisting of Ceftriaxon 2 grams plus Gentamycine 5mg/kg i.v. per day until drainage of the opacified liver segments has been achieved. Antibiotic treatment of cholangitis must include Ceftriaxon 2 grams and Gentamycine 5mg/kg i.v per day as long as the patient is admitted to the hospital.
Surgical treatment following both drainage procedures:
Surgery will be performed 4 weeks after biliary drainage (6 weeks when portal vein embolisation is indicated). The procedure is performed according to current guidelines.|
|- Primary outcome||The combined incidence of severe complications related to EBD or PTBD between the initial drainage after treatment allocation (i.e. the index drainage procedure) and the day of explorative laparotomy. A severe complication is defined as any complication related to biliary drainage, requiring an additional invasive or surgical intervention with subsequent prolonged hospital stay or death, or readmission for drainage related morbidity.|
|- Secondary outcome||- Technical success of the index drainage procedure; defined as appropriate stent/catheter placement through the stenosis into the segments of the FRL after maximum 2 procedures. |
- Time (days) from treatment allocation until therapeutic success.
- Number of procedures required to achieve therapeutic success.
- Adequate biliary drainage for explorative laparotomy; defined as a serum Bilirubin level below 50 μmol/L measured at the day before explorative laparotomy.
- Number of drainage interventions; defined as the total number of preoperative biliary drainage procedures that include stent (re-)placement or attempts at stent placement.
- Time from drainage until explorative laparotomy; defined as the number of days between inclusion and explorative laparotomy.
- All surgical procedures will be scheduled at standardised time intervals to allow analysis of the time to explorative laparotomy. However, some patients may experience a delay in surgery due to organisational issues. Therefore, the number of patients with rescheduled laparotomy for clinical reasons (i.e. the patients physical condition does not allow surgery) will also be an outcome measure. Patients with postponed laparotomies for organisational reasons are not included in this outcome measure.
- Quality of Life; assessed using the Short-Form Health Survey (SF-36), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-30), the EORTC QOL module for cholangiocarcinoma and gallbladder cancer (EORTC QLQ-BIL21), and the EuroQol 5D (EQ-5D).
- 90-day post-laparotomy mortality.
- 90-day post-laparotomy morbidity.
|- Timepoints||Therapeutic success: control ultrasonography of the liver 7 days after index drainage procedure and control bilirubin 7 and 14 days after index drainage procedure.|
Quality of life (SF-36, EORTC QLQ-30, EORTC QLQ-BIL21, EQ-5D): date of inclusion (baseline), 7, 28 and 60 days after index drainage procedure.
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES||Prof. dr. T.M. Gulik, van|
|- CONTACT for SCIENTIFIC QUERIES||Prof. dr. T.M. Gulik, van|
|- Sponsor/Initiator ||Academic Medical Center (AMC), Amsterdam|
(Source(s) of Monetary or Material Support)
|- Brief summary||Cholestasis is a significant risk factor in the treatment of patients with suspected hilar cholangiocarcinoma (HCCA) requiring major liver resection. Preoperative biliary drainage (PBD) attenuates the effects of cholestasis caused by the tumor, but there is controversy over the preferred technique of PBD, either via endoscopic biliary drainage (EBD) or using percutaneous transhepatic biliary drainage (PTBD).
The objective of this multi-center randomized controlled trial is to identify a difference in the incidence of drainage related complications between EBD and PTBD for preoperative biliary drainage of HCCA.
Inclusion criteria: Suspicion of resectable HCCA; serum bilirubine >50 Ámol/l; inadequate biliary drainage of the future remnant liver.
Main exclusion criteria: Incomplete recovery from side effects of any prior stenting procedure; contraindication for major surgery.
Intervention: Patients will be allocated to undergo either EBD or PTBD.
Primary endpoint: The incidence of severe drainage related complications between the index drainage procedure and explorative laparotomy, defined as any complication requiring an additional invasive intervention or hospital admission.
Secondary endpoints: Technical success of stent insertion; the time from drainage until explorative laparotomy; number of rescheduled laparotomies for clinical reasons; length of hospital stay; number of invasive procedures; post-laparotomy morbidity and mortality; quality of life.
This study is expected to identify PTBD as the preferred technique of preoperative biliary drainage for resectable HCCA on the basis of fewer drainage related complications and consequential better quality of life. Furthermore postoperative mortality and morbidity is expected to decrease with PTBD compared to EBD.
|- Main changes (audit trail)||17-jun-2014: |
- Diagnosis or suspicion of perihilar cholangiocarcinoma (pHCCA)
- No apparent signs of irresectability on CT-scan and/or MRI, and scheduled to undergo a ôcurativeö liver resection (may need additional lymph node biopsies or a diagnostic laparoscopy to further determine resectability)
- Incomplete recovery from side-effects of any prior stenting attempt
- Signs of active cholangitis, defined as Leukocytes ≥ 10 *109/L or antibiotic treatment for a
suspicion of cholangitis within the past 5 days
- ECOG/WHO score ≥3
Crossover treatment applies to patients who require a repeat or revision procedure, but in whom
the allocated drainage modality is no longer technically feasible. Cross-over treatment from EBD
to PTBD is protocol mandatory if EBD is unsuccessful to achieve technical success after 2
Antibiotics: Standard antibiotic prophylaxes are administered at the start of each biliary drainage procedure, according to local protocol. Prophylactic antibiotic treatments must be similar for endoscopic and percutaneous biliary drainage procedures in each centre. Cholangitis is treated with intravenous
antibiotics, preferably 2 grams ceftriaxone i.v plus gentamicine 5mg/kg, during hospital admission.
PRIMARY OUTCOME (aanvulling)
When explorative laparotomy is cancelled a substitute endpoint will be used in analysis of the
primary endpoint: (1) the total number of severe drainage-related complications between
randomization and 1 week after biopsy in patients in whom the laparotomy is cancelled due to a
diagnosis of distant metastatic disease, or (2) the total number of severe drainage-related
complications within 3 months after randomization in patients in whom the laparotomy is cancelled
due to physical deterioration.
- Individual components of the primary endpoint (special interest to incidence of cholangitis)
Therapeutic success: control ultrasound of the liver 7 days after index drainage procedure and control
bilirubin 7 and 14 days after index drainage procedure.
Quality of life (EORTC QLQ-30, EORTC QLQ-BIL21, EQ-5D): date of inclusion (baseline), 7, 28 and
90 days after index drainage procedure. - AB
|- RECORD||11-okt-2013 - 7-sep-2016|