Trans-drain Occlusion for Postoperative Pancreatic Fistula- A Double Blind Randomized Clinical Trial

Study Overview
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Brief Summary
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This is a multicenter, investigator initiated, prospective, superiority, parallel-group, randomized, double-blinded trial that aims to compare the efficacy and safety of trans-drain occlusion followed by gradual withdrawal of drain versus gradual withdrawal of drain alone for postoperative pancreatic fistula (POPF) that persists for longer than 21 days.

Detailed Description
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The most common major complication after pancreatic resection is postoperative pancreatic fistula (POPF), which is defined as a drain output of any measurable volume of fluid on and after postoperative day 3 with an amylase content > 3 times the upper limit of normal serum level. Gradual withdrawal of surgically placed drains in patients who are clinically stable and tolerate a diet is generally adopted to hasten closure of POPF. For high-output fistulas (> 150-200 mL of amylase-rich fluid per day), patients are initially managed with fasting and enteral or parenteral nutrition. If fistula output decreases substantially with these measures and the patient remains clinically well, drain withdrawal is initiated and oral intake is slowly restarted. If the patient remains well despite high fistula output, drains are slowly withdrawn in an attempt to decrease the output and close the fistula. When the output decrease to less than 10 mL per day, the drains are removed. However, the current standard practice of gradual drain withdrawal is time consuming. Although clinically stable can be discharged with the drain, the drainage tube often remains in place for a prolonged period, with patient discomfort and increased medical cost. In a pilot study by the investigators, 32.5% (37/114) of POPF patients required drainage for longer than 21 days. Besides, there is also considerable risk of recurrent fluid collection along the drain tube tract after drain removal. The investigators' experience has shown that trans-drain occlusion of the drain tract achieves fistula closure, enabling immediate removal of the drain. In a pilot study, 20 patients underwent trans-catheter occlusion for POPFs that persisted for more than 3 weeks after placement of drainage tubes. No subjective symptoms or abnormalities in blood tests were noted in 17 patients after the procedure. Three patients had abdominal pain without signs of infection, and the pain spontaneously subsided after conservative treatment. POPF healed immediately after occlusion in all of the 20 patients without recurrence during follow-up. This multicenter, investigator initiated, prospective, superiority, parallel-group, randomized, double-blinded trial aims to compare the efficacy and safety of trans-drain occlusion followed by gradual withdrawal of drain versus gradual withdrawal of drain alone for POPF that persists for longer than 21 days.

Official Title
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Trans-drain Occlusion for Postoperative Pancreatic Fistula- A Double Blind Randomized Clinical Trial

Conditions
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Pancreatic Fistula

Intervention / Treatment
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* Procedure: Fistulography and trans-drain occlusion
* Procedure: Fistulography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who undergo pancreatectomy (including pancreatoduodenectomy with or without pylorus preservation, distal pancreatectomy, and central pancreatectomy) and develop POPF that persists for 3 weeks after its occurrence. With POPF that persists for 3 weeks after occurrence Exclusion Criteria: Younger than 20 years of age Active infection not adequately controlled [body temperature ≧38.5℃ and/or eukocytosis (WBC count >15,000 /uL)/leukopenia (WBC count <4,000 /uL)], have residual intra-abdominal fluid collection (largest diameter > 4cm) despite tube drainage on CT scan (with or without contrast, performed when the patient meet inclusion criteria). Current or history of severe heart, lung, kidney, or liver failure Karnofsky Performance Score <60 Pregnant or lactating Have received somatostatin or its analogue in the index admission Decline to participate

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Enrolled patients will be randomly assigned in a 2:1 ratio to receive trans-drain occlusion followed by gradual drain withdrawal or gradual drain withdrawal.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fistulography and trans-drain occlusion<br>Fistulography is performed to assess the condition of the fistula, and trans-drain occlusion is performed by injecting glue (NBCA and Lipiodol) through the drain to occlude the tract. | Procedure: Fistulography and trans-drain occlusion<br>* Fistulography: an 18G needle is inserted into the tube and diluted contrast medium is slowly injected into the tube. Trans-drain occlusion: a 0.035-inch guidewire is inserted via the puncture needle. The drain tube is removed, cut at 4 cm proximal to the skin fixation site, and preserved for reinsertion. After inserting a 40cm 5Fr KMP catheter over the guidewire, the guidewire is removed. Afte rinsing the KMP catheter with 3ml 5% glucose water, withdraw the catheter and simultaneously inject glue (33%, 1:2, 0.5ml of NBCA + 1ml Lipiodol) into the catheter until the proximal 5cm of the catheter remains inside the tract. The guidewire is re-inserted through the catheter, and then the original drain tube is re-inserted over the guidewire. The guidewire is removed and the drain is fixed.<br>|
| Sham Comparator: Fistulography<br>Fistulography is performed to assess the condition of the fistula, without trains-drain occlusion. | Procedure: Fistulography<br>* Fistulography: an 18G needle is inserted into the tube and diluted contrast medium is slowly injected into the tube.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days to fistula closure | Days from the randomly allocated treatment to fistula closure | The date of fistula closure is the date on which the drain is removed after an output of ≦ 10 mL during 48 hours, without recurrence of fistula within the next 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30-day fistula closure rate | Proportion of patients in whom the drain can be removed by 30 days after occurrence of fistula, without recurrence within the next 3 months | From enrollment to 4 months after fistula occurrence | 
| Rate of persistent or recurrent POPF after initial drain removal | Proportion of patients with fluid collection on follow-up CT, which is to be performed at 3 months after removal of drain or when recurrence of fistula is suspected clinically. | From drain removal to 3 months after drain removal or recurrence of fistula, whichever occurs first | 
| Length of hospital stay after the assigned treatment | Days from the assigned treatment to discharge | From treatment to discharge from the index admission, an average of 2 weeks | 
| Hospital costs after the assigned treatment | Costs from the assigned treatment to discharge | From treatment to discharge from the index admission, an average of 2 weeks | 
| Rate of fistula-related complications | Proportion of patients who develop fever/infection, ileus, postpancreatectomy hemorrhage from the assigned treatment to end of follow-up. | From occurrence of fistula to 3 months after drain removal |