<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01731821</url>
  </required_header>
  <id_info>
    <org_study_id>PCI001</org_study_id>
    <nct_id>NCT01731821</nct_id>
  </id_info>
  <brief_title>Nonstented Stump-closed vs Duct-to-Mucosa Pancreaticojejunostomy After Pancreaticoduodenectomy</brief_title>
  <official_title>A Prospective Randomized Clinical Trial of Two Surgical Techniques for Pancreaticojejunostomy in Patients Undergoing Pancreaticoduodenectomy: Nonstented Stump-closed vs Duct-to-Mucosa Pancreaticojejunostomy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fudan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fudan University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pancreaticojejunostomy is the key procedure of pancreaticoduodenectomy. The aim of our study&#xD;
      is to investigate a new pancreaticojejunal (PJ) anastomosis procedure named &quot;nonstented&#xD;
      stump-closed pancreaticojejunostomy&quot; in pancreatoduodenectomy, which could provide a feasible&#xD;
      option to pancreatic surgeons for patients with pancreaticoduodenectomy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pancreaticoduodenectomy is a standard surgical approach for resectable pancreatic tumors and&#xD;
      periampullary tumors. It is considered a safe procedure resulting from the continuous&#xD;
      improvement in surgical techniques over the years. Although postoperative mortality has&#xD;
      obviously decreased, pancreatic fistula is still a major challenge in pancreatic surgery and&#xD;
      remains the major cause of postoperative morbidity and mortality after&#xD;
      pancreaticoduodenectomy(PD), ranging from 5% to 30%.&#xD;
&#xD;
      Many risks factors have been shown to cause pancreatic fistula(PF) after the operation,&#xD;
      including advanced age, prolonged operation time, intraoperative hemorrhage, BMI, soft&#xD;
      pancreas, size of the main pancreatic duct and texture of the remnant pancreas. Among them,&#xD;
      soft pancreatic texture without a dilated main pancreatic duct is regarded as the most&#xD;
      important risk factor in predicting pancreatic fistula.&#xD;
&#xD;
      The serious consequences of pancreatic fistula result from the pancreatic juice becoming&#xD;
      activated by the bile and intestinal fluid, which will eventually corrupt the PJ anastomosis&#xD;
      and the surrounding normal tissues. The corrosion of the vasculature will lead to lethal&#xD;
      hemorrhage, which is the main cause of mortality after pancreaticoduodenectomy. Furthermore,&#xD;
      pancreatin, together with the bacteria in the alimentary tract, will lead to intra-abdominal&#xD;
      infection and abscess. To reduce the pancreatic fistula rate, several techniques have been&#xD;
      described as alternatives to the conventional PJ anastomosis. Duct-to-mucosa sutures, binding&#xD;
      pancreaticojejunostomy and end-to-side invaginated fashion are widely used in the current&#xD;
      clinical setting. Some non-randomized studies showed that the duct-to-mucosa method was a&#xD;
      relatively safe approach. However, the prospective clinical study found that in comparison&#xD;
      with the conventional end-to-side anastomosis, duct-to-mucosa did not obviously decrease the&#xD;
      incidence of pancreatic fistula as well as other operative complications. The Peng's binding&#xD;
      anastomosis technique might be relatively simple to operate and have shorter operative time,&#xD;
      but as the raw pancreatic surface is exposed to the jejunal lumen directly after the&#xD;
      reconstruction, the activated pancreatic juice might lead to hemorrhage through vascular&#xD;
      corrosion. Moreover, a wide or large pancreatic stump will not fit the size of the jejunal&#xD;
      lumen, which could lead to anastomosis ischemia and leakage. The duct-to-mucosa method is not&#xD;
      affected by the size of pancreatic remnant and the jejunal lumen. The seromuscular layer of&#xD;
      the jejunum covers the pancreatic stump completely and will lower the incidence of&#xD;
      postoperative hemorrhage. It was proved to be superior to invagination anastomosis in terms&#xD;
      of anastomotic patency and function. Unfortunately, in the cases of small main pancreatic&#xD;
      duct or normal soft pancreas, the duct-to-mucosa approach is difficult to operate and takes&#xD;
      more surgery time, while simultaneously increasing the incidence of postoperative pancreatic&#xD;
      fistula(POPF). Therefore, it is difficult to find a single superior strategy that applies to&#xD;
      every case. Selecting an optimal pancreaticojejunal anastomotic method should be based on the&#xD;
      different textures of pancreas and the various sizes of the main pancreatic duct.&#xD;
&#xD;
      The postoperative pancreatic fistula (POPF), which determines postoperative mortality, length&#xD;
      of hospital stay， is dependent of its definition, and is reported in up to 16% of patients.&#xD;
      The purpose of this study is to determine whether the new anastomosis called &quot;nonstented&#xD;
      stump-closed&quot; pancreaticojejunostomy can reduce the POPF rate and downgrade compared with the&#xD;
      common accepted duct-to-mucosa pancreaticojejunostomy after pancreaticoduodenectomy. This&#xD;
      single-centre, open, randomized controlled trail is conducted following International Study&#xD;
      Group on Pancreatic Fistula (ISGPF) criteria for pancreatic fistula (PF). The primary&#xD;
      endpoint is the POPF rate, and others include overall postoperative complication rate and&#xD;
      their severity reoperation rate and hospital stay.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      Through the comparison with classic pancreatic duct-to-mucosa anastomosis, to evaluate&#xD;
      whether &quot;nonstented stump closed&quot; pancreaticojejunal anastomosis can reduce the pancreatic&#xD;
      fistula and other complications incidence; to evaluated the safety and maneuverability.&#xD;
&#xD;
      Patients and methods :all patients diagnosed with periampullar occupations which should be&#xD;
      resected through pancreaticoduodenectomy will be evaluated before surgery, including&#xD;
      CT,Magnetic Resonance(MR), Ultrasound B ,blood biochemical checks and cardiac and thoracical&#xD;
      evaluations. Before the surgery, the patients are divided into two groups by randomization.&#xD;
      After the pancreaticoduodenectomy, the randomization number decided the procedure of the&#xD;
      pancreaticojejunostomy.&#xD;
&#xD;
      Staging investigations will be standard and will include:&#xD;
&#xD;
      pancreatic enhanced CT; magnetic resonance cholangiopancreatography(MRCP); PET-CT if&#xD;
      necessary;&#xD;
&#xD;
      Randomization:&#xD;
&#xD;
      Block randomization will be done using a computer generated sheet. Randomization will be&#xD;
      performed 1 day before the operation.&#xD;
&#xD;
      All surgeries will be performed under general anesthesia with epidural analgesia. The surgery&#xD;
      will be either performed by or under the direct supervision of pancreatic surgeons with&#xD;
      experience in pancreaticojejunostomy surgery. Operative time, blood loss, blood product&#xD;
      replacement and all intraoperative details will be recorded in the proforma. Patients will be&#xD;
      shifted postoperatively to the anesthesia care unit (PCU) for observation and subsequently to&#xD;
      the recovery or high dependency ward once stabilized. Postoperative details including period&#xD;
      of postoperative pancreatic fistula,biliary leakage,postoperative haemorrhage,postoperative&#xD;
      pancreatitis , hospital stay and other complications will be recorded. Postoperative&#xD;
      mortality will be defined as 30-day mortality plus death before discharge after surgery.&#xD;
&#xD;
      Data management: All collected data will be entered into a statistical software package for&#xD;
      subsequent analysis&#xD;
&#xD;
      Main research variables:&#xD;
&#xD;
      Primary Outcome :&#xD;
&#xD;
      The primary endpoint will be the postoperative pancreatic fistula(POPF) rate.&#xD;
&#xD;
      Secondary Outcome Measures:&#xD;
&#xD;
      postoperative hospital stay time; anastomosis time; reoperation rate; morbidity&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">October 2014</completion_date>
  <primary_completion_date type="Actual">June 2014</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>the postoperative pancreatic fistula(POPF) rate</measure>
    <time_frame>30 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>postoperative hospital stay time;</measure>
    <time_frame>90 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>anastomosis time;</measure>
    <time_frame>1 hour</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>reoperation rate;</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>morbidity and mortality</measure>
    <time_frame>90 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">308</enrollment>
  <condition>Pancreatic Neoplasms</condition>
  <condition>Biliary Tract Neoplasms</condition>
  <condition>Pancreatitis, Chronic</condition>
  <condition>Duodenal Neoplasms</condition>
  <arm_group>
    <arm_group_label>Nonstented stump-closed anastomosis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nonstented stump-closed anastomosis is used for pancreaticojejunostomy after pancreaticoduodenectomy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Duct-to-mucosa anastomosis</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Duct-to-mucosa technique is used for pancreaticojejunostomy after pancreaticoduodenectomy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>pancreaticojejunostomy</intervention_name>
    <description>Nonstented stump closed pancreaticojejunostomy:&#xD;
Close the pancreatic stump with interrupted inverting sutures around the &quot;papillary-like&quot; pancreatic duct.&#xD;
A small full-thickness enterotomy was penetrated on the jejunal wall for connecting to the &quot;papillary-like&quot; pancreatic duct by placing 4-6 sutures from the &quot;periductal&quot; parenchyma to the whole-layer jejunum hole. After that, interrupted sutures between the front wall of pancreatic stump and the seromuscular jejunum were performed by 4-0 absorbable sutures to complete the anastomosis.&#xD;
Duct-to-mucosa pancreaticojejunostomy:Two layer anatomosis with &quot;Duct-to-Mucosa&quot; pancreaticojejunostomy is performed by suturing the pancreatic parenchyma to the jejunal seromuscular layer and no stenting tube was used.</description>
    <arm_group_label>Duct-to-mucosa anastomosis</arm_group_label>
    <arm_group_label>Nonstented stump-closed anastomosis</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
          -  18-80 years old;&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group(ECOG) 0-2&#xD;
&#xD;
          -  Patients must have undergone pancreaticoduodenectomy.&#xD;
&#xD;
          -  Preoperative enhanced CT scan shows respectable or borderline resectable neoplasm&#xD;
&#xD;
          -  Without distal metastasis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have had previous pancreatic body tail resection rese&#xD;
&#xD;
          -  immunodeficiency, people infected with HIV&#xD;
&#xD;
          -  patients with severe cardiopulmonary function, liver and renal function&#xD;
&#xD;
          -  infection without control or active infections&#xD;
&#xD;
          -  Pregnant patients.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xian-Jun Yu, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Pancreatic &amp; Hepatobiliary Surgery</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fudan University Shanghai Cancer Center</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2014</verification_date>
  <study_first_submitted>November 10, 2012</study_first_submitted>
  <study_first_submitted_qc>November 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2012</study_first_posted>
  <last_update_submitted>December 2, 2014</last_update_submitted>
  <last_update_submitted_qc>December 2, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 4, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fudan University</investigator_affiliation>
    <investigator_full_name>Xian-Jun Yu</investigator_full_name>
    <investigator_title>Professor and Chair,Department of Pancreatic &amp; Hepatobiliary Surgery</investigator_title>
  </responsible_party>
  <keyword>Pancreaticoduodenectomy</keyword>
  <keyword>Pancreaticojejunostomy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Pancreatic Neoplasms</mesh_term>
    <mesh_term>Biliary Tract Neoplasms</mesh_term>
    <mesh_term>Duodenal Neoplasms</mesh_term>
    <mesh_term>Pancreatitis</mesh_term>
    <mesh_term>Pancreatitis, Chronic</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01731821
org study id: PCI001
nct id: NCT01731821
lead sponsor: 
has dmc: No
Pancreaticojejunostomy is the key procedure of pancreaticoduodenectomy. The aim of our study
      is to investigate a new pancreaticojejunal (PJ) anastomosis procedure named "nonstented
      stump-closed pancreaticojejunostomy" in pancreatoduodenectomy, which could provide a feasible
      option to pancreatic surgeons for patients with pancreaticoduodenectomy.
Pancreaticoduodenectomy is a standard surgical approach for resectable pancreatic tumors and
      periampullary tumors. It is considered a safe procedure resulting from the continuous
      improvement in surgical techniques over the years. Although postoperative mortality has
      obviously decreased, pancreatic fistula is still a major challenge in pancreatic surgery and
      remains the major cause of postoperative morbidity and mortality after
      pancreaticoduodenectomy(PD), ranging from 5% to 30%.

      Many risks factors have been shown to cause pancreatic fistula(PF) after the operation,
      including advanced age, prolonged operation time, intraoperative hemorrhage, BMI, soft
      pancreas, size of the main pancreatic duct and texture of the remnant pancreas. Among them,
      soft pancreatic texture without a dilated main pancreatic duct is regarded as the most
      important risk factor in predicting pancreatic fistula.

      The serious consequences of pancreatic fistula result from the pancreatic juice becoming
      activated by the bile and intestinal fluid, which will eventually corrupt the PJ anastomosis
      and the surrounding normal tissues. The corrosion of the vasculature will lead to lethal
      hemorrhage, which is the main cause of mortality after pancreaticoduodenectomy. Furthermore,
      pancreatin, together with the bacteria in the alimentary tract, will lead to intra-abdominal
      infection and abscess. To reduce the pancreatic fistula rate, several techniques have been
      described as alternatives to the conventional PJ anastomosis. Duct-to-mucosa sutures, binding
      pancreaticojejunostomy and end-to-side invaginated fashion are widely used in the current
      clinical setting. Some non-randomized studies showed that the duct-to-mucosa method was a
      relatively safe approach. However, the prospective clinical study found that in comparison
      with the conventional end-to-side anastomosis, duct-to-mucosa did not obviously decrease the
      incidence of pancreatic fistula as well as other operative complications. The Peng's binding
      anastomosis technique might be relatively simple to operate and have shorter operative time,
      but as the raw pancreatic surface is exposed to the jejunal lumen directly after the
      reconstruction, the activated pancreatic juice might lead to hemorrhage through vascular
      corrosion. Moreover, a wide or large pancreatic stump will not fit the size of the jejunal
      lumen, which could lead to anastomosis ischemia and leakage. The duct-to-mucosa method is not
      affected by the size of pancreatic remnant and the jejunal lumen. The seromuscular layer of
      the jejunum covers the pancreatic stump completely and will lower the incidence of
      postoperative hemorrhage. It was proved to be superior to invagination anastomosis in terms
      of anastomotic patency and function. Unfortunately, in the cases of small main pancreatic
      duct or normal soft pancreas, the duct-to-mucosa approach is difficult to operate and takes
      more surgery time, while simultaneously increasing the incidence of postoperative pancreatic
      fistula(POPF). Therefore, it is difficult to find a single superior strategy that applies to
      every case. Selecting an optimal pancreaticojejunal anastomotic method should be based on the
      different textures of pancreas and the various sizes of the main pancreatic duct.

      The postoperative pancreatic fistula (POPF), which determines postoperative mortality, length
      of hospital stay， is dependent of its definition, and is reported in up to 16% of patients.
      The purpose of this study is to determine whether the new anastomosis called "nonstented
      stump-closed" pancreaticojejunostomy can reduce the POPF rate and downgrade compared with the
      common accepted duct-to-mucosa pancreaticojejunostomy after pancreaticoduodenectomy. This
      single-centre, open, randomized controlled trail is conducted following International Study
      Group on Pancreatic Fistula (ISGPF) criteria for pancreatic fistula (PF). The primary
      endpoint is the POPF rate, and others include overall postoperative complication rate and
      their severity reoperation rate and hospital stay.

      Objectives:

      Through the comparison with classic pancreatic duct-to-mucosa anastomosis, to evaluate
      whether "nonstented stump closed" pancreaticojejunal anastomosis can reduce the pancreatic
      fistula and other complications incidence; to evaluated the safety and maneuverability.

      Patients and methods :all patients diagnosed with periampullar occupations which should be
      resected through pancreaticoduodenectomy will be evaluated before surgery, including
      CT,Magnetic Resonance(MR), Ultrasound B ,blood biochemical checks and cardiac and thoracical
      evaluations. Before the surgery, the patients are divided into two groups by randomization.
      After the pancreaticoduodenectomy, the randomization number decided the procedure of the
      pancreaticojejunostomy.

      Staging investigations will be standard and will include:

      pancreatic enhanced CT; magnetic resonance cholangiopancreatography(MRCP); PET-CT if
      necessary;

      Randomization:

      Block randomization will be done using a computer generated sheet. Randomization will be
      performed 1 day before the operation.

      All surgeries will be performed under general anesthesia with epidural analgesia. The surgery
      will be either performed by or under the direct supervision of pancreatic surgeons with
      experience in pancreaticojejunostomy surgery. Operative time, blood loss, blood product
      replacement and all intraoperative details will be recorded in the proforma. Patients will be
      shifted postoperatively to the anesthesia care unit (PCU) for observation and subsequently to
      the recovery or high dependency ward once stabilized. Postoperative details including period
      of postoperative pancreatic fistula,biliary leakage,postoperative haemorrhage,postoperative
      pancreatitis , hospital stay and other complications will be recorded. Postoperative
      mortality will be defined as 30-day mortality plus death before discharge after surgery.

      Data management: All collected data will be entered into a statistical software package for
      subsequent analysis

      Main research variables:

      Primary Outcome :

      The primary endpoint will be the postoperative pancreatic fistula(POPF) rate.

      Secondary Outcome Measures:

      postoperative hospital stay time; anastomosis time; reoperation rate; morbidity
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: the postoperative pancreatic fistula(POPF) rate
time frame: 30 days
measure: postoperative hospital stay time;
time frame: 90 days
measure: anastomosis time;
time frame: 1 hour
measure: reoperation rate;
time frame: 30 days
measure: morbidity and mortality
time frame: 90 days
arm group label: Nonstented stump-closed anastomosis
arm group type: Experimental
description: Nonstented stump-closed anastomosis is used for pancreaticojejunostomy after pancreaticoduodenectomy.
arm group label: Duct-to-mucosa anastomosis
arm group type: Active Comparator
description: Duct-to-mucosa technique is used for pancreaticojejunostomy after pancreaticoduodenectomy.
intervention type: Procedure
intervention name: pancreaticojejunostomy
description: Nonstented stump closed pancreaticojejunostomy:
Close the pancreatic stump with interrupted inverting sutures around the "papillary-like" pancreatic duct.
A small full-thickness enterotomy was penetrated on the jejunal wall for connecting to the "papillary-like" pancreatic duct by placing 4-6 sutures from the "periductal" parenchyma to the whole-layer jejunum hole. After that, interrupted sutures between the front wall of pancreatic stump and the seromuscular jejunum were performed by 4-0 absorbable sutures to complete the anastomosis.
Duct-to-mucosa pancreaticojejunostomy:Two layer anatomosis with "Duct-to-Mucosa" pancreaticojejunostomy is performed by suturing the pancreatic parenchyma to the jejunal seromuscular layer and no stenting tube was used.
arm group label: Duct-to-mucosa anastomosis
arm group label: Nonstented stump-closed anastomosis
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Xian-Jun Yu, M.D.
role: Principal Investigator
affiliation: Department of Pancreatic & Hepatobiliary Surgery
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Fudan University
investigator full name: Xian-Jun Yu
investigator title: Professor and Chair,Department of Pancreatic & Hepatobiliary Surgery
mesh term: Neoplasms
mesh term: Pancreatic Neoplasms
mesh term: Biliary Tract Neoplasms
mesh term: Duodenal Neoplasms
mesh term: Pancreatitis
mesh term: Pancreatitis, Chronic