<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/NCT01707810</url>
  </required_header>
  <id_info>
    <org_study_id>LIVER TRANSPLANT OUTFLOW</org_study_id>
    <nct_id>NCT01707810</nct_id>
  </id_info>
  <brief_title>Prospective Trial Comparing Conventional Versus Piggyback Method in Venous Drainage of the Transplanted Liver</brief_title>
  <acronym>LTx-outflow</acronym>
  <official_title>Prospective Randomized Trial Comparing the Clinical Efficiency of Conventional Versus Piggyback Method in Venous Drainage of the Transplanted Liver</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fundação de Amparo à Pesquisa do Estado de São Paulo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Sao Paulo</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      METHODS: Patients were submitted to conventional (n=15) or piggyback (n=17) liver&#xD;
      transplantation (LTx). Free hepatic vein pressure (FHVP) and the central venous pressure&#xD;
      (CVP) measurements were performed after graft reperfusion. Postoperative (PO) serum&#xD;
      creatinine (Cr) was measured, acute renal failure (ARF) was defined as Cr &gt; or = 2,0mg/dL and&#xD;
      PO renal function was analyzed by modificated RIFLE-AKIN. PO overall Cr was calculated by&#xD;
      area under the curve (AUC) of Cr vs. time. on the first week.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Thirty-two patients recruited among liver transplant recipients submitted to surgery at the&#xD;
      Liver Unit at the Hospital das Clínicas of the University of São Paulo Medical School between&#xD;
      8 th October, 1999 and 30 rd September, 2000 were studied. The patients were assigned by&#xD;
      randomization to two groups: transplant performed using the conventional or the piggyback&#xD;
      method. These patients are part of a larger clinical trial where pulmonary alterations are&#xD;
      compared between patients operated using the conventional method with venovenous bypass and&#xD;
      the piggyback method.(10) Inclusion criteria admitted of both genders, aged 18 years or&#xD;
      older, submitted to a first elective LTx, with no clinical or technical reasons justifying a&#xD;
      preferential option by conventional or piggyback method. For this reason, we excluded&#xD;
      patients submitted to living donor LTx, in whom IVC is routinely preserved and those with&#xD;
      familial amyloidotic polyneuropathy, whom, in our routine, are routinely submitted to&#xD;
      conventional LTx.&#xD;
&#xD;
      The randomization process was performed by a team of nurses not involved with the&#xD;
      intraoperative care of the patients. This was obtained by &quot;coin-tossing&quot;. In each case,&#xD;
      randomization was paired according to the Child-Pugh's Score, calculated immediately before&#xD;
      surgery. Stratification was performed by blocking randomization in each subset of patient&#xD;
      (scores A, B, or C), with blocks of size 2 with a one-to-one allocation ratio. Thus, while&#xD;
      the first patient of each Child-Pugh score was effectively randomized, the second was&#xD;
      automatically allocated to the opposite surgical method, completing a pair. However, the&#xD;
      investigators had no influence on the second recipient selection due to the characteristics&#xD;
      of the organ allocation system in Brazil, former MELD scale criteria was introduced. In that&#xD;
      time, the graft distribution was according to four distinct blood groups (A,B,AB,O) generated&#xD;
      a greater obstacle to predicting who would be the next patient as related to what would be&#xD;
      obtained if blocks of 4 size have been used.&#xD;
&#xD;
      Surgeries of donor and of recipient were performed with small adaptations in the usual&#xD;
      technique in order to evaluate the pressure gradient between the hepatic vein and the right&#xD;
      atrium in the two groups. In the conventional method IVC was clamped during the anhepatic&#xD;
      phase and venous return was maintained by a portal femoral axillary venovenous bypass with a&#xD;
      centrifugal pump. In these cases, IVC reconstruction was performed by end-to-end anastomosis&#xD;
      above and below the liver. In the piggyback method IVC was not clamped in any case.&#xD;
      Implantation method of the grafted IVC in recipient IVC was not standardized, being defined&#xD;
      by the responsible surgeon during the procedure. In the two groups, all patients were&#xD;
      submitted to simultaneous arterial and portal revascularization, according to the routine of&#xD;
      the service.&#xD;
&#xD;
      Free hepatic vein pressure (FHVP) was measured using an 8F polyethylene catheter with a&#xD;
      multiperforated distal end, which was positioned in the graft's right hepatic vein during ex&#xD;
      situ preparation on the back table. The proximal end of this catheter was exteriorized in the&#xD;
      infrahepatic portion of IVC. In the conventional group, exteriorization was performed through&#xD;
      the anastomosis suture. In the piggyback group, IVC was ligated around the catheter. Central&#xD;
      venous pressure (CVP) was obtained using a Swan-Ganz catheter (routine procedure).&#xD;
      Measurement of hepatic vein and right atrium pressure was made once, after concluding biliary&#xD;
      anastomosis.&#xD;
&#xD;
      All measurements were obtained with the same transducer, determining as zero reference level&#xD;
      the median axillary line. Pressure measurement was performed in apnea in order to avoid that&#xD;
      the patient's respiratory incursions would determine oscillations in the pressure curve. When&#xD;
      oscillations persisted in spite of this maneuver, the arithmetic mean of the observed maximum&#xD;
      and minimum values was recorded. &quot;hepatic venous block&quot; was considered when a pressure&#xD;
      gradient higher than 3 mm Hg was present.(4) Serum creatinine (Cr) was determined in the&#xD;
      preoperatory period (immediately before surgery), on postoperative days (PO) 1 to 7 and on&#xD;
      14, 21 and 28. Occurrence of acute renal failure (ARF) was defined as postoperative&#xD;
      creatinine peak &gt; or = 2.0. (8) For each case, the area under the curve (AUC) Cr vs. time,&#xD;
      calculated by the trapezoidal method (11) and divided by the postoperative observation time&#xD;
      (28 days), was used as a postoperative overall creatinine parameter. Each group, conventional&#xD;
      and piggyback, are also analyzed according to the RIFLE which classifies ARF in three grades&#xD;
      of increasing severity: risk (class R), injury (class I) and failure (class F) - and two&#xD;
      outcome classes - loss and end-stage kidney disease. RIFLE classification provides these&#xD;
      grades based on changes in either Cr or urine output from the baseline condition. The RIFLE&#xD;
      criteria is an important tool to help the international community compare data on ARF and was&#xD;
      validated elsewhere (12, 13), being modified in 2005 as RIFLE-AKIN (14). For statistical&#xD;
      analysis, in this study, the Class R are unified with the group of patients without renal&#xD;
      injuries (considered as nule alterations), and the patients with class I and F were unified.&#xD;
      The outcome classes are late consequences of the LTx and were not studied in the present&#xD;
      clinical trial.&#xD;
&#xD;
      Postoperative massive ascites was considered as abdominal fluid accumulation with a volume&#xD;
      over 500 ml/day for more than 30 days (6) evaluated through body weight, abdominal drain&#xD;
      output or paracentesis.&#xD;
&#xD;
      The patients were followed up until 30 rd June, 2006, recording the date of death of those&#xD;
      who died.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 1999</start_date>
  <completion_date type="Actual">October 2000</completion_date>
  <primary_completion_date type="Actual">September 2000</primary_completion_date>
  <phase>N/A</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>Hepatic vein and right atrium pressure measurements (observed FHPV-CVP gradient values)</measure>
    <time_frame>intraoperatory</time_frame>
    <description>Free hepatic vein pressure (FHVP) was measured using an 8F polyethylene catheter with a multiperforated distal end, which was positioned in the graft's right hepatic vein during ex situ preparation on the back table. The proximal end of this catheter was exteriorized in the infrahepatic portion of IVC. In the conventional group, exteriorization was performed through the anastomosis suture. In the piggyback group, IVC was ligated around the catheter. Central venous pressure (CVP) was obtained using a Swan-Ganz catheter (routine procedure). Measurement of hepatic vein and right atrium pressure was made once, after concluding biliary anastomosis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum Creatinine</measure>
    <time_frame>postoperative days (PO) 1 to 7 and on 14, 21 and 28</time_frame>
    <description>Serum creatinine (Cr) was determined in the preoperatory period (immediately before surgery), on postoperative days (PO) 1 to 7 and on 14, 21 and 28. Occurrence of acute renal failure (ARF) was defined as postoperative creatinine peak &gt; or = 2.0</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>End-stage Liver Disease</condition>
  <arm_group>
    <arm_group_label>Conventional method</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>In the conventional method IVC was clamped during the anhepatic phase and venous return was maintained by a portal femoral axillary venovenous bypass with a centrifugal pump. In these cases, IVC reconstruction was performed by end-to-end anastomosis above and below the liver.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Piggyback method</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In the piggyback method IVC was not clamped in any case. Implantation method of the grafted IVC in recipient IVC was not standardized, being defined by the responsible surgeon during the procedure. In the two groups, all patients were submitted to simultaneous arterial and portal revascularization, according to the routine of the service.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Piggyback method</intervention_name>
    <description>In the piggyback method IVC was not clamped in any case. Implantation method of the grafted IVC in recipient IVC was not standardized, being defined by the responsible surgeon during the procedure. In the two groups, all patients were submitted to simultaneous arterial and portal revascularization, according to the routine of the service.</description>
    <arm_group_label>Piggyback method</arm_group_label>
    <other_name>Liver transplantaton piggyback method</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>conventional method</intervention_name>
    <arm_group_label>Conventional method</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Inclusion criteria admitted of both genders, aged 18 years or older, submitted to a&#xD;
             first elective LTx, with no clinical or technical reasons justifying a preferential&#xD;
             option by conventional or piggyback method&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients submitted to living donor LTx, in whom IVC is routinely preserved and those&#xD;
             with familial amyloidotic polyneuropathy, whom, in our routine, are routinely&#xD;
             submitted to conventional LTx.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paulo CB Massarollo, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Faculdade de Medicina da Universidade de São Paulo</affiliation>
  </overall_official>
  <verification_date>October 2012</verification_date>
  <study_first_submitted>October 12, 2012</study_first_submitted>
  <study_first_submitted_qc>October 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 16, 2012</study_first_posted>
  <last_update_submitted>October 15, 2012</last_update_submitted>
  <last_update_submitted_qc>October 15, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 16, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Sao Paulo</investigator_affiliation>
    <investigator_full_name>Paulo Celso Bosco Massarollo</investigator_full_name>
    <investigator_title>PhD</investigator_title>
  </responsible_party>
  <keyword>Liver transplatation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>End Stage Liver Disease</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/NCT01707810
org study id: LIVER TRANSPLANT OUTFLOW
nct id: NCT01707810
lead sponsor: 
collaborator: 
has dmc: No
METHODS: Patients were submitted to conventional (n=15) or piggyback (n=17) liver
      transplantation (LTx). Free hepatic vein pressure (FHVP) and the central venous pressure
      (CVP) measurements were performed after graft reperfusion. Postoperative (PO) serum
      creatinine (Cr) was measured, acute renal failure (ARF) was defined as Cr > or = 2,0mg/dL and
      PO renal function was analyzed by modificated RIFLE-AKIN. PO overall Cr was calculated by
      area under the curve (AUC) of Cr vs. time. on the first week.
Thirty-two patients recruited among liver transplant recipients submitted to surgery at the
      Liver Unit at the Hospital das Clínicas of the University of São Paulo Medical School between
      8 th October, 1999 and 30 rd September, 2000 were studied. The patients were assigned by
      randomization to two groups: transplant performed using the conventional or the piggyback
      method. These patients are part of a larger clinical trial where pulmonary alterations are
      compared between patients operated using the conventional method with venovenous bypass and
      the piggyback method.(10) Inclusion criteria admitted of both genders, aged 18 years or
      older, submitted to a first elective LTx, with no clinical or technical reasons justifying a
      preferential option by conventional or piggyback method. For this reason, we excluded
      patients submitted to living donor LTx, in whom IVC is routinely preserved and those with
      familial amyloidotic polyneuropathy, whom, in our routine, are routinely submitted to
      conventional LTx.

      The randomization process was performed by a team of nurses not involved with the
      intraoperative care of the patients. This was obtained by "coin-tossing". In each case,
      randomization was paired according to the Child-Pugh's Score, calculated immediately before
      surgery. Stratification was performed by blocking randomization in each subset of patient
      (scores A, B, or C), with blocks of size 2 with a one-to-one allocation ratio. Thus, while
      the first patient of each Child-Pugh score was effectively randomized, the second was
      automatically allocated to the opposite surgical method, completing a pair. However, the
      investigators had no influence on the second recipient selection due to the characteristics
      of the organ allocation system in Brazil, former MELD scale criteria was introduced. In that
      time, the graft distribution was according to four distinct blood groups (A,B,AB,O) generated
      a greater obstacle to predicting who would be the next patient as related to what would be
      obtained if blocks of 4 size have been used.

      Surgeries of donor and of recipient were performed with small adaptations in the usual
      technique in order to evaluate the pressure gradient between the hepatic vein and the right
      atrium in the two groups. In the conventional method IVC was clamped during the anhepatic
      phase and venous return was maintained by a portal femoral axillary venovenous bypass with a
      centrifugal pump. In these cases, IVC reconstruction was performed by end-to-end anastomosis
      above and below the liver. In the piggyback method IVC was not clamped in any case.
      Implantation method of the grafted IVC in recipient IVC was not standardized, being defined
      by the responsible surgeon during the procedure. In the two groups, all patients were
      submitted to simultaneous arterial and portal revascularization, according to the routine of
      the service.

      Free hepatic vein pressure (FHVP) was measured using an 8F polyethylene catheter with a
      multiperforated distal end, which was positioned in the graft's right hepatic vein during ex
      situ preparation on the back table. The proximal end of this catheter was exteriorized in the
      infrahepatic portion of IVC. In the conventional group, exteriorization was performed through
      the anastomosis suture. In the piggyback group, IVC was ligated around the catheter. Central
      venous pressure (CVP) was obtained using a Swan-Ganz catheter (routine procedure).
      Measurement of hepatic vein and right atrium pressure was made once, after concluding biliary
      anastomosis.

      All measurements were obtained with the same transducer, determining as zero reference level
      the median axillary line. Pressure measurement was performed in apnea in order to avoid that
      the patient's respiratory incursions would determine oscillations in the pressure curve. When
      oscillations persisted in spite of this maneuver, the arithmetic mean of the observed maximum
      and minimum values was recorded. "hepatic venous block" was considered when a pressure
      gradient higher than 3 mm Hg was present.(4) Serum creatinine (Cr) was determined in the
      preoperatory period (immediately before surgery), on postoperative days (PO) 1 to 7 and on
      14, 21 and 28. Occurrence of acute renal failure (ARF) was defined as postoperative
      creatinine peak > or = 2.0. (8) For each case, the area under the curve (AUC) Cr vs. time,
      calculated by the trapezoidal method (11) and divided by the postoperative observation time
      (28 days), was used as a postoperative overall creatinine parameter. Each group, conventional
      and piggyback, are also analyzed according to the RIFLE which classifies ARF in three grades
      of increasing severity: risk (class R), injury (class I) and failure (class F) - and two
      outcome classes - loss and end-stage kidney disease. RIFLE classification provides these
      grades based on changes in either Cr or urine output from the baseline condition. The RIFLE
      criteria is an important tool to help the international community compare data on ARF and was
      validated elsewhere (12, 13), being modified in 2005 as RIFLE-AKIN (14). For statistical
      analysis, in this study, the Class R are unified with the group of patients without renal
      injuries (considered as nule alterations), and the patients with class I and F were unified.
      The outcome classes are late consequences of the LTx and were not studied in the present
      clinical trial.

      Postoperative massive ascites was considered as abdominal fluid accumulation with a volume
      over 500 ml/day for more than 30 days (6) evaluated through body weight, abdominal drain
      output or paracentesis.

      The patients were followed up until 30 rd June, 2006, recording the date of death of those
      who died.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Hepatic vein and right atrium pressure measurements (observed FHPV-CVP gradient values)
time frame: intraoperatory
description: Free hepatic vein pressure (FHVP) was measured using an 8F polyethylene catheter with a multiperforated distal end, which was positioned in the graft's right hepatic vein during ex situ preparation on the back table. The proximal end of this catheter was exteriorized in the infrahepatic portion of IVC. In the conventional group, exteriorization was performed through the anastomosis suture. In the piggyback group, IVC was ligated around the catheter. Central venous pressure (CVP) was obtained using a Swan-Ganz catheter (routine procedure). Measurement of hepatic vein and right atrium pressure was made once, after concluding biliary anastomosis.
measure: Serum Creatinine
time frame: postoperative days (PO) 1 to 7 and on 14, 21 and 28
description: Serum creatinine (Cr) was determined in the preoperatory period (immediately before surgery), on postoperative days (PO) 1 to 7 and on 14, 21 and 28. Occurrence of acute renal failure (ARF) was defined as postoperative creatinine peak > or = 2.0
arm group label: Conventional method
arm group type: Sham Comparator
description: In the conventional method IVC was clamped during the anhepatic phase and venous return was maintained by a portal femoral axillary venovenous bypass with a centrifugal pump. In these cases, IVC reconstruction was performed by end-to-end anastomosis above and below the liver.
arm group label: Piggyback method
arm group type: Experimental
description: In the piggyback method IVC was not clamped in any case. Implantation method of the grafted IVC in recipient IVC was not standardized, being defined by the responsible surgeon during the procedure. In the two groups, all patients were submitted to simultaneous arterial and portal revascularization, according to the routine of the service.
intervention type: Procedure
intervention name: Piggyback method
description: In the piggyback method IVC was not clamped in any case. Implantation method of the grafted IVC in recipient IVC was not standardized, being defined by the responsible surgeon during the procedure. In the two groups, all patients were submitted to simultaneous arterial and portal revascularization, according to the routine of the service.
arm group label: Piggyback method
other name: Liver transplantaton piggyback method
intervention type: Procedure
intervention name: conventional method
arm group label: Conventional method
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paulo CB Massarollo, PhD
role: Study Chair
affiliation: Faculdade de Medicina da Universidade de São Paulo
responsible party type: Principal Investigator
investigator affiliation: University of Sao Paulo
investigator full name: Paulo Celso Bosco Massarollo
investigator title: PhD
mesh term: Liver Diseases
mesh term: End Stage Liver Disease