<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/NCT03034850</url>
  </required_header>
  <id_info>
    <org_study_id>B37120154199</org_study_id>
    <nct_id>NCT03034850</nct_id>
  </id_info>
  <brief_title>Thrombin Generation and Platelet Activation in CRS/HIPEC</brief_title>
  <official_title>Thrombin Generation and Platelet Activation in Cytoreductive Surgery Combined With Hyperthermic Intraperitoneal Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ziekenhuis Oost-Limburg</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ziekenhuis Oost-Limburg</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cytoreductive surgery (CRS) with hyperthermic intraperitoneal peroperative chemotherapy&#xD;
      (HIPEC), indicated for patients with peritoneal metastases from digestive or gynecological&#xD;
      malignancies alike, demonstrates a considerable impact on hemostatic metabolism, both on&#xD;
      platelet and on coagulation level. The potential hemostatic interference in CRS and HIPEC is&#xD;
      phase dependent. This study demonstrates the combined use of ROTEM (rotational&#xD;
      thromboelastometry), PACT (platelet activation test) and CAT (thrombin generation test)&#xD;
      assays during CRS and HIPEC with a follow-up of 7 days postoperative.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study was to quantitatively assess the impact of CRS and HIPEC, on&#xD;
      various components of hemostasis. Routine laboratory assays such as activated clotting time,&#xD;
      activated partial thromboplastin time, prothrombin time, or platelet count might, as&#xD;
      demonstrated previously, insufficiently provide specificity and/or sensitivity to assess&#xD;
      coagulation and platelet disorders. Therefore, additionally thrombin generation (TG) was&#xD;
      analyzed by the calibrated automated thrombogram assay (CAT). Also, platelet function was&#xD;
      quantitatively assessed by the PAC-t-UB assay and rotational thromboelastometry (ROTEM) was&#xD;
      used to elucidate the contribution of platelets, intrinsic and extrinsic coagulation pathways&#xD;
      in peri-operative bleeding. The hypothesis of this study was that the procedure exposed an&#xD;
      increased thrombotic risk, resulting in a faster and increased TG and hyper platelet&#xD;
      function?&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2015</start_date>
  <completion_date type="Actual">July 2016</completion_date>
  <primary_completion_date type="Actual">July 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Blood loss</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Blood loss and administration of red blood cells, fresh frozen plasma and platelets. Blood loss is quantitatively assessed based on surgical drainage volume measurements, recorded every hour. Once the surgical drains are removed (average 7 days), blood loss is quantified by hemodynamic instability and abrupt, significant decrease of hemoglobin concentration. Blood loss is assessed from the date of CRS/HIPEC surgery until 7 days postoperative or date of death from any cause, whichever came first.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Red blood cell count</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>EDTA-anticoagulated blood was used for cytometric analysis using a whole blood counter Sysmex XE 2100® (Sysmex,Kobe, Japan) to obtain a whole blood count. (million cells/mcL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>White blood cell count</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>EDTA-anticoagulated blood was used for cytometric analysis using a whole blood counter Sysmex XE 2100® (Sysmex,Kobe, Japan) to obtain a whole blood count. (cells/mcL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet count</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>EDTA-anticoagulated blood was used for cytometric analysis using a whole blood counter Sysmex XE 2100® (Sysmex,Kobe, Japan) to obtain a whole blood count. (platelets/mcL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fibrinogen levels</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Fibrinogen levels were determined with an ACL-9000 (Diamond Diagnostics, Holliston, MA) coagulation analyser. (g/dL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prothrombin Time (PT)</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Prothrombin time was measured using an ACL-9000 coagulation analyser (sec).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Activated Partial Thromboplastin Time (aPTT)</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Activated Partial Thromboplastin Time was measured using an ACL-9000 coagulation analyser (sec).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endogenous Thrombin Potential (Thrombin generation assay (CAT))</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>TG in plasma, measured with the calibrated automated thrombogram (CAT) . Briefly, 80 μl platelet poor plasma (PPP) was mixed with 20 μl of a mixture containing tissue factor (Dade-Behring) at a final concentration of 1 pM and phospholipid vesicles (f.c. 4 μM 20 mol% phosphatidylserine, 60 mol% phosphatidylcholine and 20 mol% phosphatidyl-ethanolamine, Avanti). To calibrator wells, 20 μl of calibrator (α2macroglobulin- thrombin complex) was added instead of TF and PL. After 10 minutes of incubation at 37°C, thrombin generation was initiated by the addition of 20 μl of the thrombin specific substrate, Z- Gly-Gly-Arg-7-amino-4-methylcoumarin (f.c. 416 μM, Bachem) and CaCl2 (f.c. 16.7 mM). Fluorescence was measured with a Fluoroscan Ascent reader (Thermo Labsystems) and data were analyzed with dedicated software (Thrombinoscope, Stago) [20]. Endogenous thrombin potential (ETP) (nM*min)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lag Time (Thrombin generation assay (CAT))</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>TG in plasma, measured with the calibrated automated thrombogram (CAT) . Briefly, 80 μl platelet poor plasma (PPP) was mixed with 20 μl of a mixture containing tissue factor (Dade-Behring) at a final concentration of 1 pM and phospholipid vesicles (f.c. 4 μM 20 mol% phosphatidylserine, 60 mol% phosphatidylcholine and 20 mol% phosphatidyl-ethanolamine, Avanti). To calibrator wells, 20 μl of calibrator (α2macroglobulin- thrombin complex) was added instead of TF and PL. After 10 minutes of incubation at 37°C, thrombin generation was initiated by the addition of 20 μl of the thrombin specific substrate, Z- Gly-Gly-Arg-7-amino-4-methylcoumarin (f.c. 416 μM, Bachem) and CaCl2 (f.c. 16.7 mM). Fluorescence was measured with a Fluoroscan Ascent reader (Thermo Labsystems) and data were analyzed with dedicated software (Thrombinoscope, Stago) [20]. lagtime (LT)(min)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time-to-Thrombin Peak (Thrombin generation assay (CAT))</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>TG in plasma, measured with the calibrated automated thrombogram (CAT) . Briefly, 80 μl platelet poor plasma (PPP) was mixed with 20 μl of a mixture containing tissue factor (Dade-Behring) at a final concentration of 1 pM and phospholipid vesicles (f.c. 4 μM 20 mol% phosphatidylserine, 60 mol% phosphatidylcholine and 20 mol% phosphatidyl-ethanolamine, Avanti). To calibrator wells, 20 μl of calibrator (α2macroglobulin- thrombin complex) was added instead of TF and PL. After 10 minutes of incubation at 37°C, thrombin generation was initiated by the addition of 20 μl of the thrombin specific substrate, Z- Gly-Gly-Arg-7-amino-4-methylcoumarin (f.c. 416 μM, Bachem) and CaCl2 (f.c. 16.7 mM). Fluorescence was measured with a Fluoroscan Ascent reader (Thermo Labsystems) and data were analyzed with dedicated software (Thrombinoscope, Stago) [20]. Time-to-Thrombin Peak (TTP)(min)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Thrombin Peak (TP) (Thrombin generation assay (CAT))</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>TG in plasma, measured with the calibrated automated thrombogram (CAT) . Briefly, 80 μl platelet poor plasma (PPP) was mixed with 20 μl of a mixture containing tissue factor (Dade-Behring) at a final concentration of 1 pM and phospholipid vesicles (f.c. 4 μM 20 mol% phosphatidylserine, 60 mol% phosphatidylcholine and 20 mol% phosphatidyl-ethanolamine, Avanti). To calibrator wells, 20 μl of calibrator (α2macroglobulin- thrombin complex) was added instead of TF and PL. After 10 minutes of incubation at 37°C, thrombin generation was initiated by the addition of 20 μl of the thrombin specific substrate, Z- Gly-Gly-Arg-7-amino-4-methylcoumarin (f.c. 416 μM, Bachem) and CaCl2 (f.c. 16.7 mM). Fluorescence was measured with a Fluoroscan Ascent reader (Thermo Labsystems) and data were analyzed with dedicated software (Thrombinoscope, Stago) [20]. Thrombin Peak (TP)(nM)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>P-selectin expression (Platelet activation test (PACT))</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Platelet activation was quantitatively assessed in un-processed blood by the PACT (Platelet activation test). Addition of specific agonists to whole blood (granule release capacity and in the aggregation potential of platelets). (1) the protease activated receptor (PAR-1) agonist thrombin receptor activator peptide, (2) the glycoprotein VI (GPVI) agonist collagen-related peptide , and (3) the P2Y12 agonist ADP. The reaction mixtures also contain three antibodies directed against GPIb, activated αIIbβ3 and P-selectin. Flow cytometry was used to distinguish between platelets and other cells on forward and sideward scatter pattern and by gating on the CD42b positive cells. Fluorescent intensity in the FITC gate and PE gate was selected to determine activated αIIbβ3 and P-selectin density, respectively, and results are expressed as median fluorescent intensity (MFI). P-selectin expression(MFI, median fluorescent intensity)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>αIIbβ3 activation (Platelet activation test (PACT))</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Platelet activation was quantitatively assessed in un-processed blood by the PACT (Platelet activation test). Addition of specific agonists to whole blood (granule release capacity and in the aggregation potential of platelets). (1) the protease activated receptor (PAR-1) agonist thrombin receptor activator peptide, (2) the glycoprotein VI (GPVI) agonist collagen-related peptide , and (3) the P2Y12 agonist ADP. The reaction mixtures also contain three antibodies directed against GPIb, activated αIIbβ3 and P-selectin. Flow cytometry was used to distinguish between platelets and other cells on forward and sideward scatter pattern and by gating on the CD42b positive cells. Fluorescent intensity in the FITC gate and PE gate was selected to determine activated αIIbβ3 and P-selectin density, respectively, and results are expressed as median fluorescent intensity (MFI). αIIbβ3 activation (MFI, median fluorescent intensity)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A5 EXTEM (Rotational thromboelastometry (ROTEM))</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: EXTEM (ref.: 503-05, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands), A5: amplitude of clot firmness 5 min after CT (mm)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A5 FIBTEM (Rotational thromboelastometry (ROTEM))</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: FIBTEM (ref.: 503-06, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands), All samples were measured within 1 h after blood collection. A5: amplitude of clot firmness 5 min after CT (mm)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A5 HEPTEM (Rotational thromboelastometry (ROTEM))</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: HEPTEM (ref.: 503-09, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. A5: amplitude of clot firmness 5 min after CT (mm)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A30 EXTEM (Rotational thromboelastometry (ROTEM))</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: EXTEM (ref.: 503-05, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. A30: amplitude of clot firmness 30 min after CT (mm)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A30 FIBTEM (Rotational thromboelastometry (ROTEM))</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: FIBTEM (ref.: 503-06, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. A30: amplitude of clot firmness 30 min after CT (mm)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A30 HEPTEM (Rotational thromboelastometry (ROTEM))</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: HEPTEM (ref.: 503-09, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. A30: amplitude of clot firmness 30 min after CT (mm)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alpha EXTEM (Rotational thromboelastometry (ROTEM))</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: EXTEM (ref.: 503-05, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. Alpha (the angle between the baseline and a tangent to the clotting curve through the 2 mm point; degree)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alpha FIBTEM (Rotational thromboelastometry (ROTEM))</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: FIBTEM (ref.: 503-06, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. Alpha (the angle between the baseline and a tangent to the clotting curve through the 2 mm point; degree)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alpha HEPTEM (Rotational thromboelastometry (ROTEM))</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: HEPTEM (ref.: 503-09, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. Alpha (the angle between the baseline and a tangent to the clotting curve through the 2 mm point; degree)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulation Time CT EXTEM (Rotational thromboelastometry (ROTEM))</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: EXTEM (ref.: 503-05, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. Coagulation Time (CT): test start until a clot firmness amplitude of 2 mm is reached; sec.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulation Time CT FIBTEM (Rotational thromboelastometry (ROTEM))</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: FIBTEM (ref.: 503-06, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands), All samples were measured within 1 h after blood collection. Coagulation Time (CT): test start until a clot firmness amplitude of 2 mm is reached; sec.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulation Time CT HEPTEM (Rotational thromboelastometry (ROTEM))</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: HEPTEM (ref.: 503-09, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. Coagulation Time (CT): test start until a clot firmness amplitude of 2 mm is reached; sec.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clot Formation Time CFT EXTEM (Rotational thromboelastometry (ROTEM)</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: EXTEM (ref.: 503-05, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands), All samples were measured within 1 h after blood collection. CFT: in seconds indicates the time between 2 and 20 mm clot firmness amplitude is achieved (sec)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clot Formation Time CFT FIBTEM (Rotational thromboelastometry (ROTEM)</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: FIBTEM (ref.: 503-06, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. CFT: in seconds indicates the time between 2 and 20 mm clot firmness amplitude is achieved (sec)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clot Formation Time CFT HEPTEM (Rotational thromboelastometry (ROTEM)</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: HEPTEM (ref.: 503-09, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. CFT: in seconds indicates the time between 2 and 20 mm clot firmness amplitude is achieved (sec)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Lysis (ML) EXTEM Rotational thromboelastometry (ROTEM)</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: EXTEM (ref.: 503-05, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. Maximum Lysis (ML; %): maximum lysis during runtime</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Lysis (ML) FIBTEM Rotational thromboelastometry (ROTEM)</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: FIBTEM (ref.: 503-06, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. Maximum Lysis (ML; %): maximum lysis during runtime</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Lysis (ML) HEPTEM Rotational thromboelastometry (ROTEM)</measure>
    <time_frame>From surgical incision to 7 days postoperative</time_frame>
    <description>Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: HEPTEM (ref.: 503-09, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Maximum Lysis (ML; %): maximum lysis during runtime</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">27</enrollment>
  <condition>Mesothelioma; Peritoneum</condition>
  <condition>Pseudomyxoma Peritonei</condition>
  <condition>Peritoneal Carcinomatosis</condition>
  <arm_group>
    <arm_group_label>CRS/HIPEC</arm_group_label>
    <description>Patients with a confirmed histological diagnosis of peritoneal disease treated by cytoreductive surgery (CRS) with hyperthermic intraperitoneal peroperative chemotherapy (HIPEC).</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>CRS/HIPEC</intervention_name>
    <description>The generic surgical approach involved peritonectomy procedures and visceral resections called CRS as described by Sugarbaker (1995). Peritoneal disease burden was assessed using the perito- neal cancer index (PCI), which scores 13 intra-abdominal sites on a scale of 0 (no disease) to 3 (lesion size &gt; 5 cm), thus giving a range of possible scores from 0 to 39. The same team performed the surgical procedure of all included patients. Before connection to the patient, the circuit was filled with dextrose 5% (2 L/m2 body surface area) and warmed to 37°C.</description>
    <arm_group_label>CRS/HIPEC</arm_group_label>
    <other_name>oxaliplatinum</other_name>
    <other_name>5-fluorouracil</other_name>
    <other_name>folinic acid</other_name>
    <other_name>cisplatinum</other_name>
    <other_name>doxorubicin</other_name>
    <other_name>ifosfamide</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        This prospective observational pilot study, scheduled between April 2015 and July 2016,&#xD;
        included 27 patients from the Ziekenhuis Oost-Limburg, Genk, Belgium, after approval by the&#xD;
        local medical ethics committee (Eudract/B nr: B371201524199) and written informed consent.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  a confirmed histological diagnosis of peritoneal disease (e.g., mesothelioma;&#xD;
             pseudomyxoma peritonei; colorectal, ovarian, or gastric peritoneal carcinomatosis of&#xD;
             colorectal, ovarian, or gastric cancer origin; or abdominal sarcomatosis); and&#xD;
&#xD;
          -  age &lt;80 years; and&#xD;
&#xD;
          -  a cardiac, renal, hepatic, and bone marrow function compatible with surgery; and&#xD;
&#xD;
          -  informed written consent to participate in the study&#xD;
&#xD;
        Exclusion Criteria:(or)&#xD;
&#xD;
          -  inherited coagulation abnormalities,&#xD;
&#xD;
          -  active systemic infections,&#xD;
&#xD;
          -  interstitial lung disease,&#xD;
&#xD;
          -  serious cardiac dysrhythmia or condition, New York Heart Association classification of&#xD;
             III or IV, congestive cardiac failure, uncontrolled hypertension (diastolic blood&#xD;
             pressure constantly &gt;100 mm Hg, systolic blood pressure constantly &gt; 180 mm Hg).&#xD;
&#xD;
          -  inadequate bone marrow function at the beginning of the trial, defined as platelet&#xD;
             count less than &lt;150 GPT/L or neutrophil granulocyte count less than &lt;1.5 GPT/L.&#xD;
&#xD;
          -  inadequate renal function at the beginning of the trial, defined as GFR less than &lt;60&#xD;
             ml/min,&#xD;
&#xD;
          -  inadequate liver function at the beginning of the trial, defined as bilirubin &gt;1.5&#xD;
             times ULN (upper limit of normal), active hepatitis B or C infection,&#xD;
&#xD;
          -  female patients who are pregnant or breast feeding&#xD;
&#xD;
          -  participation in another therapeutic clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sven Van Poucke, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ziekenhuis Oost-Limburg</affiliation>
  </overall_official>
  <link>
    <url>http://www.cancercenter.com/treatments/hipec/</url>
    <description>Hyperthermic intraperitoneal chemotherapy</description>
  </link>
  <reference>
    <citation>Sugarbaker PH. Peritonectomy procedures. Ann Surg. 1995 Jan;221(1):29-42. doi: 10.1097/00000658-199501000-00004.</citation>
    <PMID>7826158</PMID>
  </reference>
  <reference>
    <citation>Elias DM, Ouellet JF. Intraperitoneal chemohyperthermia: rationale, technique, indications, and results. Surg Oncol Clin N Am. 2001 Oct;10(4):915-33, xi.</citation>
    <PMID>11641098</PMID>
  </reference>
  <reference>
    <citation>Van der Speeten K, Govaerts K, Stuart OA, Sugarbaker PH. Pharmacokinetics of the perioperative use of cancer chemotherapy in peritoneal surface malignancy patients. Gastroenterol Res Pract. 2012;2012:378064. doi: 10.1155/2012/378064. Epub 2012 Jun 13.</citation>
    <PMID>22778722</PMID>
  </reference>
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  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 12, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 27, 2017</study_first_posted>
  <last_update_submitted>January 24, 2017</last_update_submitted>
  <last_update_submitted_qc>January 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 27, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ziekenhuis Oost-Limburg</investigator_affiliation>
    <investigator_full_name>Sven Van Poucke</investigator_full_name>
    <investigator_title>Medical Doctor, Anesthesiologist, Emergency Physician</investigator_title>
  </responsible_party>
  <keyword>cytoreductive surgery</keyword>
  <keyword>hyperthermic intraperitoneal peroperative chemotherapy</keyword>
  <keyword>platelet function</keyword>
  <keyword>thrombin generation</keyword>
  <keyword>thromboelastometry</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mesothelioma</mesh_term>
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Peritoneal Neoplasms</mesh_term>
    <mesh_term>Pseudomyxoma Peritonei</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Ifosfamide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All de-identified data will be available 6 months after inclusion of the last patient by contacting the principle investigator (svanpoucke@gmail.com). Once the results of the study are available and published, all data will be part of the publication.</ipd_description>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_type>Study Protocol</doc_type>
      <doc_url>https://drive.google.com/open?id=0B0qo2hDQpXhncWZFZkNfZXhZMjVuUGcxc0IzZll5TEtjaXdn</doc_url>
    </study_doc>
    <study_doc>
      <doc_id>eudract/B-nr B37120154199</doc_id>
      <doc_type>Advice Ethical Committee</doc_type>
      <doc_url>https://drive.google.com/open?id=0B0qo2hDQpXhnU3AzRHY0d1NtVmlsSmx1cFhKOGtKLTVscno0</doc_url>
    </study_doc>
  </study_docs>
  <!-- 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/NCT03034850
org study id: B37120154199
nct id: NCT03034850
lead sponsor: 
has dmc: No
Cytoreductive surgery (CRS) with hyperthermic intraperitoneal peroperative chemotherapy
      (HIPEC), indicated for patients with peritoneal metastases from digestive or gynecological
      malignancies alike, demonstrates a considerable impact on hemostatic metabolism, both on
      platelet and on coagulation level. The potential hemostatic interference in CRS and HIPEC is
      phase dependent. This study demonstrates the combined use of ROTEM (rotational
      thromboelastometry), PACT (platelet activation test) and CAT (thrombin generation test)
      assays during CRS and HIPEC with a follow-up of 7 days postoperative.
The purpose of this study was to quantitatively assess the impact of CRS and HIPEC, on
      various components of hemostasis. Routine laboratory assays such as activated clotting time,
      activated partial thromboplastin time, prothrombin time, or platelet count might, as
      demonstrated previously, insufficiently provide specificity and/or sensitivity to assess
      coagulation and platelet disorders. Therefore, additionally thrombin generation (TG) was
      analyzed by the calibrated automated thrombogram assay (CAT). Also, platelet function was
      quantitatively assessed by the PAC-t-UB assay and rotational thromboelastometry (ROTEM) was
      used to elucidate the contribution of platelets, intrinsic and extrinsic coagulation pathways
      in peri-operative bleeding. The hypothesis of this study was that the procedure exposed an
      increased thrombotic risk, resulting in a faster and increased TG and hyper platelet
      function?
observational model: Cohort
time perspective: Prospective
measure: Blood loss
time frame: From surgical incision to 7 days postoperative
description: Blood loss and administration of red blood cells, fresh frozen plasma and platelets. Blood loss is quantitatively assessed based on surgical drainage volume measurements, recorded every hour. Once the surgical drains are removed (average 7 days), blood loss is quantified by hemodynamic instability and abrupt, significant decrease of hemoglobin concentration. Blood loss is assessed from the date of CRS/HIPEC surgery until 7 days postoperative or date of death from any cause, whichever came first.
measure: Red blood cell count
time frame: From surgical incision to 7 days postoperative
description: EDTA-anticoagulated blood was used for cytometric analysis using a whole blood counter Sysmex XE 2100® (Sysmex,Kobe, Japan) to obtain a whole blood count. (million cells/mcL)
measure: White blood cell count
time frame: From surgical incision to 7 days postoperative
description: EDTA-anticoagulated blood was used for cytometric analysis using a whole blood counter Sysmex XE 2100® (Sysmex,Kobe, Japan) to obtain a whole blood count. (cells/mcL)
measure: Platelet count
time frame: From surgical incision to 7 days postoperative
description: EDTA-anticoagulated blood was used for cytometric analysis using a whole blood counter Sysmex XE 2100® (Sysmex,Kobe, Japan) to obtain a whole blood count. (platelets/mcL)
measure: Fibrinogen levels
time frame: From surgical incision to 7 days postoperative
description: Fibrinogen levels were determined with an ACL-9000 (Diamond Diagnostics, Holliston, MA) coagulation analyser. (g/dL)
measure: Prothrombin Time (PT)
time frame: From surgical incision to 7 days postoperative
description: Prothrombin time was measured using an ACL-9000 coagulation analyser (sec).
measure: Activated Partial Thromboplastin Time (aPTT)
time frame: From surgical incision to 7 days postoperative
description: Activated Partial Thromboplastin Time was measured using an ACL-9000 coagulation analyser (sec).
measure: Endogenous Thrombin Potential (Thrombin generation assay (CAT))
time frame: From surgical incision to 7 days postoperative
description: TG in plasma, measured with the calibrated automated thrombogram (CAT) . Briefly, 80 μl platelet poor plasma (PPP) was mixed with 20 μl of a mixture containing tissue factor (Dade-Behring) at a final concentration of 1 pM and phospholipid vesicles (f.c. 4 μM 20 mol% phosphatidylserine, 60 mol% phosphatidylcholine and 20 mol% phosphatidyl-ethanolamine, Avanti). To calibrator wells, 20 μl of calibrator (α2macroglobulin- thrombin complex) was added instead of TF and PL. After 10 minutes of incubation at 37°C, thrombin generation was initiated by the addition of 20 μl of the thrombin specific substrate, Z- Gly-Gly-Arg-7-amino-4-methylcoumarin (f.c. 416 μM, Bachem) and CaCl2 (f.c. 16.7 mM). Fluorescence was measured with a Fluoroscan Ascent reader (Thermo Labsystems) and data were analyzed with dedicated software (Thrombinoscope, Stago) [20]. Endogenous thrombin potential (ETP) (nM*min)
measure: Lag Time (Thrombin generation assay (CAT))
time frame: From surgical incision to 7 days postoperative
description: TG in plasma, measured with the calibrated automated thrombogram (CAT) . Briefly, 80 μl platelet poor plasma (PPP) was mixed with 20 μl of a mixture containing tissue factor (Dade-Behring) at a final concentration of 1 pM and phospholipid vesicles (f.c. 4 μM 20 mol% phosphatidylserine, 60 mol% phosphatidylcholine and 20 mol% phosphatidyl-ethanolamine, Avanti). To calibrator wells, 20 μl of calibrator (α2macroglobulin- thrombin complex) was added instead of TF and PL. After 10 minutes of incubation at 37°C, thrombin generation was initiated by the addition of 20 μl of the thrombin specific substrate, Z- Gly-Gly-Arg-7-amino-4-methylcoumarin (f.c. 416 μM, Bachem) and CaCl2 (f.c. 16.7 mM). Fluorescence was measured with a Fluoroscan Ascent reader (Thermo Labsystems) and data were analyzed with dedicated software (Thrombinoscope, Stago) [20]. lagtime (LT)(min)
measure: Time-to-Thrombin Peak (Thrombin generation assay (CAT))
time frame: From surgical incision to 7 days postoperative
description: TG in plasma, measured with the calibrated automated thrombogram (CAT) . Briefly, 80 μl platelet poor plasma (PPP) was mixed with 20 μl of a mixture containing tissue factor (Dade-Behring) at a final concentration of 1 pM and phospholipid vesicles (f.c. 4 μM 20 mol% phosphatidylserine, 60 mol% phosphatidylcholine and 20 mol% phosphatidyl-ethanolamine, Avanti). To calibrator wells, 20 μl of calibrator (α2macroglobulin- thrombin complex) was added instead of TF and PL. After 10 minutes of incubation at 37°C, thrombin generation was initiated by the addition of 20 μl of the thrombin specific substrate, Z- Gly-Gly-Arg-7-amino-4-methylcoumarin (f.c. 416 μM, Bachem) and CaCl2 (f.c. 16.7 mM). Fluorescence was measured with a Fluoroscan Ascent reader (Thermo Labsystems) and data were analyzed with dedicated software (Thrombinoscope, Stago) [20]. Time-to-Thrombin Peak (TTP)(min)
measure: Thrombin Peak (TP) (Thrombin generation assay (CAT))
time frame: From surgical incision to 7 days postoperative
description: TG in plasma, measured with the calibrated automated thrombogram (CAT) . Briefly, 80 μl platelet poor plasma (PPP) was mixed with 20 μl of a mixture containing tissue factor (Dade-Behring) at a final concentration of 1 pM and phospholipid vesicles (f.c. 4 μM 20 mol% phosphatidylserine, 60 mol% phosphatidylcholine and 20 mol% phosphatidyl-ethanolamine, Avanti). To calibrator wells, 20 μl of calibrator (α2macroglobulin- thrombin complex) was added instead of TF and PL. After 10 minutes of incubation at 37°C, thrombin generation was initiated by the addition of 20 μl of the thrombin specific substrate, Z- Gly-Gly-Arg-7-amino-4-methylcoumarin (f.c. 416 μM, Bachem) and CaCl2 (f.c. 16.7 mM). Fluorescence was measured with a Fluoroscan Ascent reader (Thermo Labsystems) and data were analyzed with dedicated software (Thrombinoscope, Stago) [20]. Thrombin Peak (TP)(nM)
measure: P-selectin expression (Platelet activation test (PACT))
time frame: From surgical incision to 7 days postoperative
description: Platelet activation was quantitatively assessed in un-processed blood by the PACT (Platelet activation test). Addition of specific agonists to whole blood (granule release capacity and in the aggregation potential of platelets). (1) the protease activated receptor (PAR-1) agonist thrombin receptor activator peptide, (2) the glycoprotein VI (GPVI) agonist collagen-related peptide , and (3) the P2Y12 agonist ADP. The reaction mixtures also contain three antibodies directed against GPIb, activated αIIbβ3 and P-selectin. Flow cytometry was used to distinguish between platelets and other cells on forward and sideward scatter pattern and by gating on the CD42b positive cells. Fluorescent intensity in the FITC gate and PE gate was selected to determine activated αIIbβ3 and P-selectin density, respectively, and results are expressed as median fluorescent intensity (MFI). P-selectin expression(MFI, median fluorescent intensity)
measure: αIIbβ3 activation (Platelet activation test (PACT))
time frame: From surgical incision to 7 days postoperative
description: Platelet activation was quantitatively assessed in un-processed blood by the PACT (Platelet activation test). Addition of specific agonists to whole blood (granule release capacity and in the aggregation potential of platelets). (1) the protease activated receptor (PAR-1) agonist thrombin receptor activator peptide, (2) the glycoprotein VI (GPVI) agonist collagen-related peptide , and (3) the P2Y12 agonist ADP. The reaction mixtures also contain three antibodies directed against GPIb, activated αIIbβ3 and P-selectin. Flow cytometry was used to distinguish between platelets and other cells on forward and sideward scatter pattern and by gating on the CD42b positive cells. Fluorescent intensity in the FITC gate and PE gate was selected to determine activated αIIbβ3 and P-selectin density, respectively, and results are expressed as median fluorescent intensity (MFI). αIIbβ3 activation (MFI, median fluorescent intensity)
measure: A5 EXTEM (Rotational thromboelastometry (ROTEM))
time frame: From surgical incision to 7 days postoperative
description: Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: EXTEM (ref.: 503-05, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands), A5: amplitude of clot firmness 5 min after CT (mm)
measure: A5 FIBTEM (Rotational thromboelastometry (ROTEM))
time frame: From surgical incision to 7 days postoperative
description: Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: FIBTEM (ref.: 503-06, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands), All samples were measured within 1 h after blood collection. A5: amplitude of clot firmness 5 min after CT (mm)
measure: A5 HEPTEM (Rotational thromboelastometry (ROTEM))
time frame: From surgical incision to 7 days postoperative
description: Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: HEPTEM (ref.: 503-09, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. A5: amplitude of clot firmness 5 min after CT (mm)
measure: A30 EXTEM (Rotational thromboelastometry (ROTEM))
time frame: From surgical incision to 7 days postoperative
description: Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: EXTEM (ref.: 503-05, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. A30: amplitude of clot firmness 30 min after CT (mm)
measure: A30 FIBTEM (Rotational thromboelastometry (ROTEM))
time frame: From surgical incision to 7 days postoperative
description: Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: FIBTEM (ref.: 503-06, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. A30: amplitude of clot firmness 30 min after CT (mm)
measure: A30 HEPTEM (Rotational thromboelastometry (ROTEM))
time frame: From surgical incision to 7 days postoperative
description: Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: HEPTEM (ref.: 503-09, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. A30: amplitude of clot firmness 30 min after CT (mm)
measure: Alpha EXTEM (Rotational thromboelastometry (ROTEM))
time frame: From surgical incision to 7 days postoperative
description: Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: EXTEM (ref.: 503-05, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. Alpha (the angle between the baseline and a tangent to the clotting curve through the 2 mm point; degree)
measure: Alpha FIBTEM (Rotational thromboelastometry (ROTEM))
time frame: From surgical incision to 7 days postoperative
description: Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: FIBTEM (ref.: 503-06, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. Alpha (the angle between the baseline and a tangent to the clotting curve through the 2 mm point; degree)
measure: Alpha HEPTEM (Rotational thromboelastometry (ROTEM))
time frame: From surgical incision to 7 days postoperative
description: Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: HEPTEM (ref.: 503-09, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. Alpha (the angle between the baseline and a tangent to the clotting curve through the 2 mm point; degree)
measure: Coagulation Time CT EXTEM (Rotational thromboelastometry (ROTEM))
time frame: From surgical incision to 7 days postoperative
description: Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: EXTEM (ref.: 503-05, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. Coagulation Time (CT): test start until a clot firmness amplitude of 2 mm is reached; sec.
measure: Coagulation Time CT FIBTEM (Rotational thromboelastometry (ROTEM))
time frame: From surgical incision to 7 days postoperative
description: Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: FIBTEM (ref.: 503-06, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands), All samples were measured within 1 h after blood collection. Coagulation Time (CT): test start until a clot firmness amplitude of 2 mm is reached; sec.
measure: Coagulation Time CT HEPTEM (Rotational thromboelastometry (ROTEM))
time frame: From surgical incision to 7 days postoperative
description: Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: HEPTEM (ref.: 503-09, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. Coagulation Time (CT): test start until a clot firmness amplitude of 2 mm is reached; sec.
measure: Clot Formation Time CFT EXTEM (Rotational thromboelastometry (ROTEM)
time frame: From surgical incision to 7 days postoperative
description: Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: EXTEM (ref.: 503-05, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands), All samples were measured within 1 h after blood collection. CFT: in seconds indicates the time between 2 and 20 mm clot firmness amplitude is achieved (sec)
measure: Clot Formation Time CFT FIBTEM (Rotational thromboelastometry (ROTEM)
time frame: From surgical incision to 7 days postoperative
description: Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: FIBTEM (ref.: 503-06, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. CFT: in seconds indicates the time between 2 and 20 mm clot firmness amplitude is achieved (sec)
measure: Clot Formation Time CFT HEPTEM (Rotational thromboelastometry (ROTEM)
time frame: From surgical incision to 7 days postoperative
description: Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: HEPTEM (ref.: 503-09, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. CFT: in seconds indicates the time between 2 and 20 mm clot firmness amplitude is achieved (sec)
measure: Maximum Lysis (ML) EXTEM Rotational thromboelastometry (ROTEM)
time frame: From surgical incision to 7 days postoperative
description: Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: EXTEM (ref.: 503-05, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. Maximum Lysis (ML; %): maximum lysis during runtime
measure: Maximum Lysis (ML) FIBTEM Rotational thromboelastometry (ROTEM)
time frame: From surgical incision to 7 days postoperative
description: Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: FIBTEM (ref.: 503-06, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). All samples were measured within 1 h after blood collection. Maximum Lysis (ML; %): maximum lysis during runtime
measure: Maximum Lysis (ML) HEPTEM Rotational thromboelastometry (ROTEM)
time frame: From surgical incision to 7 days postoperative
description: Thrombus formation was measured by ROTEM (Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Standard assays were used according to the manufacturer's recommendations: HEPTEM (ref.: 503-09, Tem International GmbH c/o Dutch Affiliate, Tilburg, The Netherlands). Maximum Lysis (ML; %): maximum lysis during runtime
arm group label: CRS/HIPEC
description: Patients with a confirmed histological diagnosis of peritoneal disease treated by cytoreductive surgery (CRS) with hyperthermic intraperitoneal peroperative chemotherapy (HIPEC).
intervention type: Procedure
intervention name: CRS/HIPEC
description: The generic surgical approach involved peritonectomy procedures and visceral resections called CRS as described by Sugarbaker (1995). Peritoneal disease burden was assessed using the perito- neal cancer index (PCI), which scores 13 intra-abdominal sites on a scale of 0 (no disease) to 3 (lesion size > 5 cm), thus giving a range of possible scores from 0 to 39. The same team performed the surgical procedure of all included patients. Before connection to the patient, the circuit was filled with dextrose 5% (2 L/m2 body surface area) and warmed to 37°C.
arm group label: CRS/HIPEC
other name: oxaliplatinum
other name: 5-fluorouracil
other name: folinic acid
other name: cisplatinum
other name: doxorubicin
other name: ifosfamide
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 80 Years
healthy volunteers: No
last name: Sven Van Poucke, MD
role: Principal Investigator
affiliation: Ziekenhuis Oost-Limburg
url: http://www.cancercenter.com/treatments/hipec/
description: Hyperthermic intraperitoneal chemotherapy
citation: Sugarbaker PH. Peritonectomy procedures. Ann Surg. 1995 Jan;221(1):29-42. doi: 10.1097/00000658-199501000-00004.
PMID: 7826158
citation: Elias DM, Ouellet JF. Intraperitoneal chemohyperthermia: rationale, technique, indications, and results. Surg Oncol Clin N Am. 2001 Oct;10(4):915-33, xi.
PMID: 11641098
citation: Van der Speeten K, Govaerts K, Stuart OA, Sugarbaker PH. Pharmacokinetics of the perioperative use of cancer chemotherapy in peritoneal surface malignancy patients. Gastroenterol Res Pract. 2012;2012:378064. doi: 10.1155/2012/378064. Epub 2012 Jun 13.
PMID: 22778722
citation: Urano M, Ling CC. Thermal enhancement of melphalan and oxaliplatin cytotoxicity in vitro. Int J Hyperthermia. 2002 Jul-Aug;18(4):307-15. doi: 10.1080/02656730210123534.
PMID: 12079586
citation: Perez-Ruixo C, Valenzuela B, Peris JE, Bretcha-Boix P, Escudero-Ortiz V, Farre-Alegre J, Perez-Ruixo JJ. Population pharmacokinetics of hyperthermic intraperitoneal oxaliplatin in patients with peritoneal carcinomatosis after cytoreductive surgery. Cancer Chemother Pharmacol. 2013 Mar;71(3):693-704. doi: 10.1007/s00280-012-2060-2. Epub 2012 Dec 30.
PMID: 23274396
citation: Schmidt C, Creutzenberg M, Piso P, Hobbhahn J, Bucher M. Peri-operative anaesthetic management of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Anaesthesia. 2008 Apr;63(4):389-95. doi: 10.1111/j.1365-2044.2007.05380.x.
PMID: 18336490
citation: Desantis M, Bernard JL, Casanova V, Cegarra-Escolano M, Benizri E, Rahili AM, Benchimol D, Bereder JM. Morbidity, mortality, and oncological outcomes of 401 consecutive cytoreductive procedures with hyperthermic intraperitoneal chemotherapy (HIPEC). Langenbecks Arch Surg. 2015 Jan;400(1):37-48. doi: 10.1007/s00423-014-1253-z. Epub 2014 Oct 16.
PMID: 25319432
citation: Kajdi ME, Beck-Schimmer B, Held U, Kofmehl R, Lehmann K, Ganter MT. Anaesthesia in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: retrospective analysis of a single centre three-year experience. World J Surg Oncol. 2014 May 1;12:136. doi: 10.1186/1477-7819-12-136.
PMID: 24886171
citation: Bell JC, Rylah BG, Chambers RW, Peet H, Mohamed F, Moran BJ. Perioperative management of patients undergoing cytoreductive surgery combined with heated intraperitoneal chemotherapy for peritoneal surface malignancy: a multi-institutional experience. Ann Surg Oncol. 2012 Dec;19(13):4244-51. doi: 10.1245/s10434-012-2496-y. Epub 2012 Jul 18.
PMID: 22805865
citation: Cooksley TJ, Haji-Michael P. Post-operative critical care management of patients undergoing cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC). World J Surg Oncol. 2011 Dec 19;9:169. doi: 10.1186/1477-7819-9-169.
PMID: 22182345
citation: Korakianitis O, Daskalou T, Alevizos L, Stamou K, Mavroudis C, Iatrou C, Vogiatzaki T, Eleftheriadis S, Tentes AA. Lack of significant intraoperative coagulopathy in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) indicates that epidural anaesthesia is a safe option. Int J Hyperthermia. 2015;31(8):857-62. doi: 10.3109/02656736.2015.1075606. Epub 2015 Oct 8.
PMID: 26446799
citation: Falcon Arana L, Fuentes-Garcia D, Roca Calvo MJ, Hernandez-Palazon J, Gil Martinez J, Cascales Campos PA, Acosta Villegas FJ, Parrilla Paricio P. Alterations in hemostasis during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis. Cir Esp. 2015 Oct;93(8):496-501. doi: 10.1016/j.ciresp.2015.01.012. Epub 2015 Apr 14. English, Spanish.
PMID: 25882334
citation: Kusamura S, Moran BJ, Sugarbaker PH, Levine EA, Elias D, Baratti D, Morris DL, Sardi A, Glehen O, Deraco M; Peritoneal Surface Oncology Group International (PSOGI). Multicentre study of the learning curve and surgical performance of cytoreductive surgery with intraperitoneal chemotherapy for pseudomyxoma peritonei. Br J Surg. 2014 Dec;101(13):1758-65. doi: 10.1002/bjs.9674. Epub 2014 Oct 20.
PMID: 25329419
citation: Canda AE, Sokmen S, Terzi C, Arslan C, Oztop I, Karabulut B, Ozzeybek D, Sarioglu S, Fuzun M. Complications and toxicities after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2013 Apr;20(4):1082-7. doi: 10.1245/s10434-012-2853-x. Epub 2013 Mar 2.
PMID: 23456387
citation: Newton AD, Bartlett EK, Karakousis GC. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a review of factors contributing to morbidity and mortality. J Gastrointest Oncol. 2016 Feb;7(1):99-111. doi: 10.3978/j.issn.2078-6891.2015.100.
PMID: 26941988
citation: Hemker HC, Giesen P, AlDieri R, Regnault V, de Smed E, Wagenvoord R, Lecompte T, Beguin S. The calibrated automated thrombogram (CAT): a universal routine test for hyper- and hypocoagulability. Pathophysiol Haemost Thromb. 2002 Sep-Dec;32(5-6):249-53. doi: 10.1159/000073575.
PMID: 13679651
citation: Roest M, van Holten TC, Fleurke GJ, Remijn JA. Platelet Activation Test in Unprocessed Blood (Pac-t-UB) to Monitor Platelet Concentrates and Whole Blood of Thrombocytopenic Patients. Transfus Med Hemother. 2013 Apr;40(2):117-25. doi: 10.1159/000350688. Epub 2013 Mar 28.
PMID: 23652405
citation: Ninivaggi M, Feijge MA, Baaten CC, Kuiper GJ, Marcus MA, Ten Cate H, Lance MD, Heemskerk JW, van der Meijden PE. Additive roles of platelets and fibrinogen in whole-blood fibrin clot formation upon dilution as assessed by thromboelastometry. Thromb Haemost. 2014 Mar 3;111(3):447-57. doi: 10.1160/TH13-06-0493. Epub 2013 Nov 21.
PMID: 24258426
citation: Etulain J, Lapponi MJ, Patrucchi SJ, Romaniuk MA, Benzadon R, Klement GL, Negrotto S, Schattner M. Hyperthermia inhibits platelet hemostatic functions and selectively regulates the release of alpha-granule proteins. J Thromb Haemost. 2011 Aug;9(8):1562-71. doi: 10.1111/j.1538-7836.2011.04394.x.
PMID: 21649851
citation: Cardenas JC, Rahbar E, Pommerening MJ, Baer LA, Matijevic N, Cotton BA, Holcomb JB, Wade CE. Measuring thrombin generation as a tool for predicting hemostatic potential and transfusion requirements following trauma. J Trauma Acute Care Surg. 2014 Dec;77(6):839-45. doi: 10.1097/TA.0000000000000348.
PMID: 25099452
citation: Kuiper GJ, Henskens YM. Rapid and Correct Prediction of Thrombocytopenia and Hypofibrinogenemia with Rotational Thromboelastometry in Cardiac Surgery Reconsidered. J Cardiothorac Vasc Anesth. 2016 Dec;30(6):e55-e56. doi: 10.1053/j.jvca.2016.04.009. Epub 2016 Apr 12. No abstract available.
PMID: 27498262
citation: Perez-Ruixo C, Valenzuela B, Peris JE, Bretcha-Boix P, Escudero-Ortiz V, Farre-Alegre J, Perez-Ruixo JJ. Platelet Dynamics in Peritoneal Carcinomatosis Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Oxaliplatin. AAPS J. 2016 Jan;18(1):239-50. doi: 10.1208/s12248-015-9839-0. Epub 2015 Nov 17.
PMID: 26577587
citation: Votanopoulos K, Ihemelandu C, Shen P, Stewart J, Russell G, Levine EA. A comparison of hematologic toxicity profiles after heated intraperitoneal chemotherapy with oxaliplatin and mitomycin C. J Surg Res. 2013 Jan;179(1):e133-9. doi: 10.1016/j.jss.2012.01.015. Epub 2012 Mar 10.
PMID: 22480844
citation: McGovern KF, Lascola KM, Smith SA, Clark-Price SC, McMichael M, Wilkins PA. Assessment of acute moderate hyperglycemia on traditional and thromboelastometry coagulation parameters in healthy adult horses. J Vet Emerg Crit Care (San Antonio). 2012 Oct;22(5):550-7. doi: 10.1111/j.1476-4431.2012.00792.x. Epub 2012 Aug 29.
PMID: 22931303
citation: Gielen CL, Grimbergen J, Klautz RJ, Koopman J, Quax PH. Fibrinogen reduction and coagulation in cardiac surgery: an investigational study. Blood Coagul Fibrinolysis. 2015 Sep;26(6):613-20. doi: 10.1097/MBC.0000000000000307.
PMID: 26083991
responsible party type: Principal Investigator
investigator affiliation: Ziekenhuis Oost-Limburg
investigator full name: Sven Van Poucke
investigator title: Medical Doctor, Anesthesiologist, Emergency Physician
mesh term: Mesothelioma
mesh term: Carcinoma
mesh term: Peritoneal Neoplasms
mesh term: Pseudomyxoma Peritonei
mesh term: Doxorubicin
mesh term: Fluorouracil
mesh term: Ifosfamide
sharing ipd: Yes
ipd description: All de-identified data will be available 6 months after inclusion of the last patient by contacting the principle investigator (svanpoucke@gmail.com). Once the results of the study are available and published, all data will be part of the publication.
study doc: 
study doc: 