<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/NCT01666366</url>
  </required_header>
  <id_info>
    <org_study_id>BITA Y vs In Situ</org_study_id>
    <nct_id>NCT01666366</nct_id>
  </id_info>
  <brief_title>Comparison Between 2 Bilateral Internal Thoracic Artery Coronary Artery Bypass Grafting Configurations</brief_title>
  <official_title>Comparison of Bilateral Internal Thoracic Artery Revascularization Using in Situ or Y Graft Configurations: a Prospective Randomized Clinical, Functional and Angiographic Evaluation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cliniques universitaires Saint-Luc- Université Catholique de Louvain</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cliniques universitaires Saint-Luc- Université Catholique de Louvain</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Bilateral internal thoracic arteries (BITA) demonstrated superiority over other grafts to the&#xD;
      left coronary system in terms of patency and survival benefit. Several BITA configurations&#xD;
      are proposed for left-sided myocardial revascularization, but the ideal BITA assemblage is&#xD;
      still unidentified.&#xD;
&#xD;
      From 03/2003 to 08/2006, 1297 consecutive patients underwent isolated bypass surgery in our&#xD;
      institution. 481 patients met the inclusion criteria for randomization and 304 (64%) were&#xD;
      randomized. Patients were allocated to BITA in situ grafting (n=147) or Y configuration&#xD;
      (n=152) then evaluated for clinical, functional, and angiographic outcome after 6 months, 3&#xD;
      and 7 years . Patient telephone interviews were conducted every 3 months and a stress test&#xD;
      performed twice yearly under the referring cardiologist's supervision. Angiographic follow-up&#xD;
      was performed 6 months after surgery. The primary and secondary end points were,&#xD;
      respectively, major adverse cerebro-cardiovascular events (MACCE) and the proportion of ITA&#xD;
      grafts that were completely occluded at follow-up angiography.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study design All patients referred for isolated surgical coronary revascularization from&#xD;
      April 2003 to July 2006 were screened according to the inclusion criteria (Table 1). Patients&#xD;
      were randomly assigned to undergo one of two alternative surgical strategies: BITA in situ&#xD;
      (LITA to the LAD and RITA to the marginal branches into the transverse sinus) or BITA Y (LITA&#xD;
      to the LAD and RITA to the marginal branches but anastomozed proximally to the LITA in a Y&#xD;
      configuration as described by Barra JA et al 3). Randomization was performed the day before&#xD;
      the operation after the patient's record was reviewed without knowledge of the preoperative&#xD;
      angiogram. Complementary grafting was performed with either a saphenous vein graft or a&#xD;
      pedicled right gastroepiloic artery depending on the location and quality of the targeted&#xD;
      coronary vessel, but also depending on the surgeon's choice. All patients were scheduled for&#xD;
      a systematic angiography at 6 and 36 months following surgery. All patients gave written&#xD;
      informed consent at the time of bypass surgery and before the angiographic investigation. The&#xD;
      study protocol was approved by the Ethics Committee at our institution.&#xD;
&#xD;
      Patients From 2003 to 2006, 1297 consecutive patients underwent isolated bypass surgery at&#xD;
      our institution. Of these, 481 patients (37%) met the inclusion criteria for enrolment in the&#xD;
      study (Figure 1). Three hundred four of 481 patients (63%) were actually randomized. The&#xD;
      remaining 177 patients were not randomized because of a) refusal of systematic angiographic&#xD;
      control (85%) and b) logistic incapacity to randomize patients (15%). BITA grafting was&#xD;
      performed with a in situ configuration in 147 patients and with a Y configuration in 152.&#xD;
      Five patients initially allocated to the BITA in situ group were excluded for protocol&#xD;
      violations. In these cases, the surgeon decided to deviate from the assigned&#xD;
      revascularisation strategy in favor of a BITA Y configuration. Patient's demographics and&#xD;
      clinical characteristics are shown in Table 2. The BITA were harvested and grafted as&#xD;
      previously described 4-5. Operative characteristics are detailed in Table 3.&#xD;
&#xD;
      Postoperative management and follow-up Patients received prophylactic low dose fractionated&#xD;
      heparin postoperatively, and 160 mg of aspirin daily starting on postoperative day 2.&#xD;
      Patients were interviewed by telephone at 3 and 6 months and then twice yearly thereafter. If&#xD;
      the patient had been hospitalized between interviews, in-patient records were obtained.&#xD;
      Patients had a systematic stress test on a cycloergometer twice a year performed under the&#xD;
      supervision of their referring cardiologist.&#xD;
&#xD;
      Follow-up angiography was scheduled at both 6 months and 3 years after surgery. Nitroglycerin&#xD;
      (2 mg) was injected into each graft before filming. At least two orthogonal views of each ITA&#xD;
      graft were obtained, with continued exposure as required to visualize distal runoff and the&#xD;
      size of the target coronary bed.&#xD;
&#xD;
      Data analysis The clinical end point was occurrence of MACCE defined as a combined end-point&#xD;
      including: death from any cause; perioperative myocardial infarction (occurring between 0 and&#xD;
      30 days); late myocardial infarction (occurring between 31 days and 6 years); additional&#xD;
      cardiac surgery; coronary angioplasty; and stroke. Myocardial infarction was defined as the&#xD;
      apparition of a new Q wave, a rise of more than 10 ng / ml of troponin in the early post&#xD;
      operative period or any episode of chest pain with typical rise and fall of cardiac enzymes&#xD;
      thereafter.&#xD;
&#xD;
      The angiographic end point was the proportion of ITA grafts that were completely occluded at&#xD;
      follow-up angiography. Complete occlusion was defined as the absence of visible opacification&#xD;
      of the target coronary vessel (TIMI flow grade 0).&#xD;
&#xD;
      All postoperative angiograms were independently reviewed by 2 investigators; discrepancies in&#xD;
      patency definition were reviewed by a third investigator and resolved by consensus.&#xD;
&#xD;
      Statistical analysis We calculated that the enrolment of at least 152 patients per group&#xD;
      would provide the study with 80% power to detect a relative reduction of 8 % in the rate of&#xD;
      graft occlusion, from an estimated 10% with BITA Y grafting 6 to 2% with BITA in situ 7&#xD;
      grafting, assuming a 20% within-patient correlation for graft occlusion, a two-tailed test,&#xD;
      and an alpha value of 0.05. Data are expressed as the mean ± 1 SD. In bivariate analyses, the&#xD;
      association of independent variables with each outcome variable was tested with Chi square&#xD;
      test for independent samples (binary variables).&#xD;
&#xD;
      All p-values are two-tailed. The Statistical Analysis Software (SAS, 9.1 releases, SAS&#xD;
      Institute Inc., SAS Campus Drive, Cary, NC USA) was used in the statistical analysis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2003</start_date>
  <completion_date type="Actual">March 2012</completion_date>
  <primary_completion_date type="Actual">August 2006</primary_completion_date>
  <phase>Phase 4</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>major adverse cerebro-cardiovascular events (MACCE)</measure>
    <time_frame>3 years</time_frame>
    <description>Data analysis The clinical end point was occurrence of MACCE defined as a combined end-point including: death from any cause; perioperative myocardial infarction (occurring between 0 and 30 days); late myocardial infarction (occurring between 31 days and 6 years); additional cardiac surgery; coronary angioplasty; and stroke. Myocardial infarction was defined as the apparition of a new Q wave, a rise of more than 10 ng / ml of troponin in the early post operative period or any episode of chest pain with typical rise and fall of cardiac enzymes thereafter.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>graft patency</measure>
    <time_frame>3 years</time_frame>
    <description>The angiographic end point was the proportion of ITA grafts that were completely occluded at follow-up angiography. Complete occlusion was defined as the absence of visible opacification of the target coronary vessel (TIMI flow grade 0).&#xD;
All postoperative angiograms were independently reviewed by 2 investigators; discrepancies in patency definition were reviewed by a third investigator and resolved by consensus.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">304</enrollment>
  <condition>Coronary Disease</condition>
  <arm_group>
    <arm_group_label>In Situ Bilateral mammary grafting</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Coronary artery bypass grafting: BITA in situ (LITA to the LAD and RITA to the marginal branches into the transverse sinus)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Y composite Bilateral mammary grafting</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Coronary artery bypass grafting: BITA Y (LITA to the LAD and RITA to the marginal branches but anastomozed proximally to the LITA in a Y configuration</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Coronary artery bypass grafting</intervention_name>
    <arm_group_label>In Situ Bilateral mammary grafting</arm_group_label>
    <arm_group_label>Y composite Bilateral mammary grafting</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Angiographic evidence of severe (&gt;70% by visual estimate) 3 vessels coronary&#xD;
             obstruction&#xD;
&#xD;
          -  Elective procedure&#xD;
&#xD;
          -  Isolated CABG&#xD;
&#xD;
          -  Age &lt;75 years and life expectancy &gt;5 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diabetes with a HbA1c &gt;7.5&#xD;
&#xD;
          -  FEV1 &lt; 60 % predicted value&#xD;
&#xD;
          -  Body mass index &gt;35&#xD;
&#xD;
          -  Reoperation&#xD;
&#xD;
          -  Other configuration then LIMA -&gt; LAD territory. RIMA -&gt; LCX territory.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Glineur, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cliniques Universitaire St Luc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cliniques Universitaire St Luc</name>
      <address>
        <city>Brussels</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <results_reference>
    <citation>Glineur D, Hanet C, Poncelet A, D'hoore W, Funken JC, Rubay J, Kefer J, Astarci P, Lacroix V, Verhelst R, Etienne PY, Noirhomme P, El Khoury G. Comparison of bilateral internal thoracic artery revascularization using in situ or Y graft configurations: a prospective randomized clinical, functional, and angiographic midterm evaluation. Circulation. 2008 Sep 30;118(14 Suppl):S216-21. doi: 10.1161/CIRCULATIONAHA.107.751933.</citation>
    <PMID>18824757</PMID>
  </results_reference>
  <verification_date>August 2012</verification_date>
  <study_first_submitted>August 1, 2012</study_first_submitted>
  <study_first_submitted_qc>August 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 16, 2012</study_first_posted>
  <last_update_submitted>August 10, 2012</last_update_submitted>
  <last_update_submitted_qc>August 10, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 16, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cliniques universitaires Saint-Luc- Université Catholique de Louvain</investigator_affiliation>
    <investigator_full_name>Glineur</investigator_full_name>
    <investigator_title>Professor David Glineur MD PhD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary 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/NCT01666366
org study id: BITA Y vs In Situ
nct id: NCT01666366
lead sponsor: 
has dmc: No
Bilateral internal thoracic arteries (BITA) demonstrated superiority over other grafts to the
      left coronary system in terms of patency and survival benefit. Several BITA configurations
      are proposed for left-sided myocardial revascularization, but the ideal BITA assemblage is
      still unidentified.

      From 03/2003 to 08/2006, 1297 consecutive patients underwent isolated bypass surgery in our
      institution. 481 patients met the inclusion criteria for randomization and 304 (64%) were
      randomized. Patients were allocated to BITA in situ grafting (n=147) or Y configuration
      (n=152) then evaluated for clinical, functional, and angiographic outcome after 6 months, 3
      and 7 years . Patient telephone interviews were conducted every 3 months and a stress test
      performed twice yearly under the referring cardiologist's supervision. Angiographic follow-up
      was performed 6 months after surgery. The primary and secondary end points were,
      respectively, major adverse cerebro-cardiovascular events (MACCE) and the proportion of ITA
      grafts that were completely occluded at follow-up angiography.
Study design All patients referred for isolated surgical coronary revascularization from
      April 2003 to July 2006 were screened according to the inclusion criteria (Table 1). Patients
      were randomly assigned to undergo one of two alternative surgical strategies: BITA in situ
      (LITA to the LAD and RITA to the marginal branches into the transverse sinus) or BITA Y (LITA
      to the LAD and RITA to the marginal branches but anastomozed proximally to the LITA in a Y
      configuration as described by Barra JA et al 3). Randomization was performed the day before
      the operation after the patient's record was reviewed without knowledge of the preoperative
      angiogram. Complementary grafting was performed with either a saphenous vein graft or a
      pedicled right gastroepiloic artery depending on the location and quality of the targeted
      coronary vessel, but also depending on the surgeon's choice. All patients were scheduled for
      a systematic angiography at 6 and 36 months following surgery. All patients gave written
      informed consent at the time of bypass surgery and before the angiographic investigation. The
      study protocol was approved by the Ethics Committee at our institution.

      Patients From 2003 to 2006, 1297 consecutive patients underwent isolated bypass surgery at
      our institution. Of these, 481 patients (37%) met the inclusion criteria for enrolment in the
      study (Figure 1). Three hundred four of 481 patients (63%) were actually randomized. The
      remaining 177 patients were not randomized because of a) refusal of systematic angiographic
      control (85%) and b) logistic incapacity to randomize patients (15%). BITA grafting was
      performed with a in situ configuration in 147 patients and with a Y configuration in 152.
      Five patients initially allocated to the BITA in situ group were excluded for protocol
      violations. In these cases, the surgeon decided to deviate from the assigned
      revascularisation strategy in favor of a BITA Y configuration. Patient's demographics and
      clinical characteristics are shown in Table 2. The BITA were harvested and grafted as
      previously described 4-5. Operative characteristics are detailed in Table 3.

      Postoperative management and follow-up Patients received prophylactic low dose fractionated
      heparin postoperatively, and 160 mg of aspirin daily starting on postoperative day 2.
      Patients were interviewed by telephone at 3 and 6 months and then twice yearly thereafter. If
      the patient had been hospitalized between interviews, in-patient records were obtained.
      Patients had a systematic stress test on a cycloergometer twice a year performed under the
      supervision of their referring cardiologist.

      Follow-up angiography was scheduled at both 6 months and 3 years after surgery. Nitroglycerin
      (2 mg) was injected into each graft before filming. At least two orthogonal views of each ITA
      graft were obtained, with continued exposure as required to visualize distal runoff and the
      size of the target coronary bed.

      Data analysis The clinical end point was occurrence of MACCE defined as a combined end-point
      including: death from any cause; perioperative myocardial infarction (occurring between 0 and
      30 days); late myocardial infarction (occurring between 31 days and 6 years); additional
      cardiac surgery; coronary angioplasty; and stroke. Myocardial infarction was defined as the
      apparition of a new Q wave, a rise of more than 10 ng / ml of troponin in the early post
      operative period or any episode of chest pain with typical rise and fall of cardiac enzymes
      thereafter.

      The angiographic end point was the proportion of ITA grafts that were completely occluded at
      follow-up angiography. Complete occlusion was defined as the absence of visible opacification
      of the target coronary vessel (TIMI flow grade 0).

      All postoperative angiograms were independently reviewed by 2 investigators; discrepancies in
      patency definition were reviewed by a third investigator and resolved by consensus.

      Statistical analysis We calculated that the enrolment of at least 152 patients per group
      would provide the study with 80% power to detect a relative reduction of 8 % in the rate of
      graft occlusion, from an estimated 10% with BITA Y grafting 6 to 2% with BITA in situ 7
      grafting, assuming a 20% within-patient correlation for graft occlusion, a two-tailed test,
      and an alpha value of 0.05. Data are expressed as the mean ± 1 SD. In bivariate analyses, the
      association of independent variables with each outcome variable was tested with Chi square
      test for independent samples (binary variables).

      All p-values are two-tailed. The Statistical Analysis Software (SAS, 9.1 releases, SAS
      Institute Inc., SAS Campus Drive, Cary, NC USA) was used in the statistical analysis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: major adverse cerebro-cardiovascular events (MACCE)
time frame: 3 years
description: Data analysis The clinical end point was occurrence of MACCE defined as a combined end-point including: death from any cause; perioperative myocardial infarction (occurring between 0 and 30 days); late myocardial infarction (occurring between 31 days and 6 years); additional cardiac surgery; coronary angioplasty; and stroke. Myocardial infarction was defined as the apparition of a new Q wave, a rise of more than 10 ng / ml of troponin in the early post operative period or any episode of chest pain with typical rise and fall of cardiac enzymes thereafter.
measure: graft patency
time frame: 3 years
description: The angiographic end point was the proportion of ITA grafts that were completely occluded at follow-up angiography. Complete occlusion was defined as the absence of visible opacification of the target coronary vessel (TIMI flow grade 0).
All postoperative angiograms were independently reviewed by 2 investigators; discrepancies in patency definition were reviewed by a third investigator and resolved by consensus.
arm group label: In Situ Bilateral mammary grafting
arm group type: Active Comparator
description: Coronary artery bypass grafting: BITA in situ (LITA to the LAD and RITA to the marginal branches into the transverse sinus)
arm group label: Y composite Bilateral mammary grafting
arm group type: Active Comparator
description: Coronary artery bypass grafting: BITA Y (LITA to the LAD and RITA to the marginal branches but anastomozed proximally to the LITA in a Y configuration
intervention type: Procedure
intervention name: Coronary artery bypass grafting
arm group label: In Situ Bilateral mammary grafting
arm group label: Y composite Bilateral mammary grafting
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: David Glineur, MD PhD
role: Principal Investigator
affiliation: Cliniques Universitaire St Luc
facility: 
country: Belgium
citation: Glineur D, Hanet C, Poncelet A, D'hoore W, Funken JC, Rubay J, Kefer J, Astarci P, Lacroix V, Verhelst R, Etienne PY, Noirhomme P, El Khoury G. Comparison of bilateral internal thoracic artery revascularization using in situ or Y graft configurations: a prospective randomized clinical, functional, and angiographic midterm evaluation. Circulation. 2008 Sep 30;118(14 Suppl):S216-21. doi: 10.1161/CIRCULATIONAHA.107.751933.
PMID: 18824757
responsible party type: Principal Investigator
investigator affiliation: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
investigator full name: Glineur
investigator title: Professor David Glineur MD PhD
mesh term: Coronary Disease