Thrombin Generation and Platelet Activation in CRS/HIPEC

NCT03034850 | Completed

• 1 other identifier: B37120154199
• Study Type: observational
• Target: 27
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Mesothelioma; Peritoneum; Pseudomyxoma Peritonei; Peritoneal Carcinomatosis

Keywords

cytoreductive surgery; hyperthermic intraperitoneal peroperative chemotherapy; platelet function; thrombin generation; thromboelastometry

Outcome Measures

Primary Outcomes (1)

• Blood loss

  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.

  From surgical incision to 7 days postoperative

Secondary Outcomes (30)

• Red blood cell count

  From surgical incision to 7 days postoperative

• White blood cell count

  From surgical incision to 7 days postoperative

• Platelet count

  From surgical incision to 7 days postoperative

• Fibrinogen levels

  From surgical incision to 7 days postoperative

• Prothrombin Time (PT)

  From surgical incision to 7 days postoperative

Study Arms (1)

CRS/HIPEC

Patients with a confirmed histological diagnosis of peritoneal disease treated by cytoreductive surgery (CRS) with hyperthermic intraperitoneal peroperative chemotherapy (HIPEC).

Procedure: CRS/HIPEC

Interventions

CRS/HIPEC PROCEDURE

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.

Also known as: oxaliplatinum, 5-fluorouracil, folinic acid, cisplatinum, doxorubicin, ifosfamide

CRS/HIPEC

Eligibility Criteria

• Age: Up to 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This prospective observational pilot study, scheduled between April 2015 and July 2016, included 27 patients from the Ziekenhuis Oost-Limburg, Genk, Belgium, after approval by the local medical ethics committee (Eudract/B nr: B371201524199) and written informed consent.

You may qualify if:

• a confirmed histological diagnosis of peritoneal disease (e.g., mesothelioma; pseudomyxoma peritonei; colorectal, ovarian, or gastric peritoneal carcinomatosis of colorectal, ovarian, or gastric cancer origin; or abdominal sarcomatosis); and
• age \<80 years; and
• a cardiac, renal, hepatic, and bone marrow function compatible with surgery; and
• informed written consent to participate in the study

You may not qualify if:

• inherited coagulation abnormalities,
• active systemic infections,
• interstitial lung disease,
• serious cardiac dysrhythmia or condition, New York Heart Association classification of III or IV, congestive cardiac failure, uncontrolled hypertension (diastolic blood pressure constantly \>100 mm Hg, systolic blood pressure constantly \> 180 mm Hg).
• inadequate bone marrow function at the beginning of the trial, defined as platelet count less than \<150 GPT/L or neutrophil granulocyte count less than \<1.5 GPT/L.
• inadequate renal function at the beginning of the trial, defined as GFR less than \<60 ml/min,
• inadequate liver function at the beginning of the trial, defined as bilirubin \>1.5 times ULN (upper limit of normal), active hepatitis B or C infection,
• female patients who are pregnant or breast feeding
• participation in another therapeutic clinical trial.

Sponsors & Collaborators

• Ziekenhuis Oost-Limburg: lead

Related Publications (25)

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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 BACKGROUND

• 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 BACKGROUND

• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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Related Links

• Hyperthermic intraperitoneal chemotherapy

MeSH Terms

Conditions

Mesothelioma; Pseudomyxoma Peritonei; Peritoneal Neoplasms

Interventions

Oxaliplatin; Fluorouracil; Leucovorin; Cisplatin; Doxorubicin; Ifosfamide

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Adenocarcinoma, Mucinous; Adenocarcinoma; Carcinoma; Neoplasms, Cystic, Mucinous, and Serous; Abdominal Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines

Study Officials

• Sven Van Poucke, MD

  Ziekenhuis Oost-Limburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor, Anesthesiologist, Emergency Physician

Study Record Dates

• First Submitted: January 12, 2017
• First Posted: January 27, 2017
• Study Start: April 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: January 27, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will share