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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.
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 If the patient remains well despite high fistula output, drains are slowly withdrawn in an attempt to decrease the output and close the fistula.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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fistulography and trans-drain occlusion | Experimental | 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. |
|
| Fistulography | Sham Comparator | Fistulography is performed to assess the condition of the fistula, without trains-drain occlusion. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fistulography and trans-drain occlusion | Procedure |
|
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | Fever/infection or pain that develops within 48 hours after the allocated treatment, or any adverse events judged to be related to the treatment | From treatment to discharge from the index admission, an average of 2 weeks |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Yu-Wen Tien, MD, PhD | National Taiwan University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Taiwan University Hospital | Taipei | 100 | Taiwan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12296891 | Background | Schlitt HJ, Schmidt U, Simunec D, Jager M, Aselmann H, Neipp M, Piso P. Morbidity and mortality associated with pancreatogastrostomy and pancreatojejunostomy following partial pancreatoduodenectomy. Br J Surg. 2002 Oct;89(10):1245-51. doi: 10.1046/j.1365-2168.2002.02202.x. | |
| 11296108 | Background | Balcom JH 4th, Rattner DW, Warshaw AL, Chang Y, Fernandez-del Castillo C. Ten-year experience with 733 pancreatic resections: changing indications, older patients, and decreasing length of hospitalization. Arch Surg. 2001 Apr;136(4):391-8. doi: 10.1001/archsurg.136.4.391. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 27, 2018 | Jan 8, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D010185 | Pancreatic Fistula |
| ID | Term |
|---|---|
| D016154 | Digestive System Fistula |
| D004066 | Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D005402 | Fistula |
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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.
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|
| Fistulography | Procedure | Fistulography: an 18G needle is inserted into the tube and diluted contrast medium is slowly injected into the tube. |
|
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 |
| 9339931 | Background | Yeo CJ, Cameron JL, Sohn TA, Lillemoe KD, Pitt HA, Talamini MA, Hruban RH, Ord SE, Sauter PK, Coleman J, Zahurak ML, Grochow LB, Abrams RA. Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s: pathology, complications, and outcomes. Ann Surg. 1997 Sep;226(3):248-57; discussion 257-60. doi: 10.1097/00000658-199709000-00004. |
| 28040257 | Background | Bassi C, Marchegiani G, Dervenis C, Sarr M, Abu Hilal M, Adham M, Allen P, Andersson R, Asbun HJ, Besselink MG, Conlon K, Del Chiaro M, Falconi M, Fernandez-Cruz L, Fernandez-Del Castillo C, Fingerhut A, Friess H, Gouma DJ, Hackert T, Izbicki J, Lillemoe KD, Neoptolemos JP, Olah A, Schulick R, Shrikhande SV, Takada T, Takaori K, Traverso W, Vollmer CM, Wolfgang CL, Yeo CJ, Salvia R, Buchler M; International Study Group on Pancreatic Surgery (ISGPS). The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After. Surgery. 2017 Mar;161(3):584-591. doi: 10.1016/j.surg.2016.11.014. Epub 2016 Dec 28. |
| 16003309 | Background | Bassi C, Dervenis C, Butturini G, Fingerhut A, Yeo C, Izbicki J, Neoptolemos J, Sarr M, Traverso W, Buchler M; International Study Group on Pancreatic Fistula Definition. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery. 2005 Jul;138(1):8-13. doi: 10.1016/j.surg.2005.05.001. |
| 25371115 | Background | Roberts KJ, Sutcliffe RP, Marudanayagam R, Hodson J, Isaac J, Muiesan P, Navarro A, Patel K, Jah A, Napetti S, Adair A, Lazaridis S, Prachalias A, Shingler G, Al-Sarireh B, Storey R, Smith AM, Shah N, Fusai G, Ahmed J, Abu Hilal M, Mirza DF. Scoring System to Predict Pancreatic Fistula After Pancreaticoduodenectomy: A UK Multicenter Study. Ann Surg. 2015 Jun;261(6):1191-7. doi: 10.1097/SLA.0000000000000997. |
| 23494109 | Background | El Nakeeb A, Salah T, Sultan A, El Hemaly M, Askr W, Ezzat H, Hamdy E, Atef E, El Hanafy E, El-Geidie A, Abdel Wahab M, Abdallah T. Pancreatic anastomotic leakage after pancreaticoduodenectomy. Risk factors, clinical predictors, and management (single center experience). World J Surg. 2013 Jun;37(6):1405-18. doi: 10.1007/s00268-013-1998-5. |
| 18490557 | Background | Veillette G, Dominguez I, Ferrone C, Thayer SP, McGrath D, Warshaw AL, Fernandez-del Castillo C. Implications and management of pancreatic fistulas following pancreaticoduodenectomy: the Massachusetts General Hospital experience. Arch Surg. 2008 May;143(5):476-81. doi: 10.1001/archsurg.143.5.476. |
| 26727086 | Background | McMillan MT, Soi S, Asbun HJ, Ball CG, Bassi C, Beane JD, Behrman SW, Berger AC, Bloomston M, Callery MP, Christein JD, Dixon E, Drebin JA, Castillo CF, Fisher WE, Fong ZV, House MG, Hughes SJ, Kent TS, Kunstman JW, Malleo G, Miller BC, Salem RR, Soares K, Valero V, Wolfgang CL, Vollmer CM Jr. Risk-adjusted Outcomes of Clinically Relevant Pancreatic Fistula Following Pancreatoduodenectomy: A Model for Performance Evaluation. Ann Surg. 2016 Aug;264(2):344-52. doi: 10.1097/SLA.0000000000001537. |
| 21529927 | Background | Diener MK, Seiler CM, Rossion I, Kleeff J, Glanemann M, Butturini G, Tomazic A, Bruns CJ, Busch OR, Farkas S, Belyaev O, Neoptolemos JP, Halloran C, Keck T, Niedergethmann M, Gellert K, Witzigmann H, Kollmar O, Langer P, Steger U, Neudecker J, Berrevoet F, Ganzera S, Heiss MM, Luntz SP, Bruckner T, Kieser M, Buchler MW. Efficacy of stapler versus hand-sewn closure after distal pancreatectomy (DISPACT): a randomised, controlled multicentre trial. Lancet. 2011 Apr 30;377(9776):1514-22. doi: 10.1016/S0140-6736(11)60237-7. |
| 26776849 | Background | Tjaden C, Hinz U, Hassenpflug M, Fritz F, Fritz S, Grenacher L, Buchler MW, Hackert T. Fluid collection after distal pancreatectomy: a frequent finding. HPB (Oxford). 2016 Jan;18(1):35-40. doi: 10.1016/j.hpb.2015.10.006. Epub 2015 Nov 18. |
| D020763 |
| Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |