Coagulation & Vitamin K in Head & Neck Microvascular Free NCT04517461

Clinical Trial Details — Status: Completed

Administrative data
NCT number	NCT04517461
Other study ID #	2020-00718
Secondary ID
Status	Completed
Phase
First received
Last updated
Start date	September 15, 2020
Est. completion date	October 1, 2021

Study information
Verified date	April 2022
Source	Region Skane
Contact	n/a
Is FDA regulated	No
Health authority
Study type	Observational

Clinical Trial Summary

For patients with large head and neck tumors the recommended treatment, in many cases, is a combination of extensive surgery and postoperative radiotherapy. The surgical procedure involves resection of the tumor and reconstruction with a so called microvascular free flap, i.e. tissue transferred from for instance the arm or leg to the resection site. Complications of this complex procedure include, but are not limited to, bleeding and blood cloths (thrombosis) in the transferred tissue (free flap), which can cause very serious complications including need for further surgery and loss of the flap. Routine blood tests can measure parts of the system that regulates bleeding and the forming of blood clots, the so called coagulation system, but these tests don't cover the whole system. There are however more advanced instruments, such as ROTEM, rotational thromboelastometry, which provide a more global view of the hemostatic potential of whole blood. ROTEM is one of few more advanced assays that can be analyzed in emergency situations in major hospitals. Other more advanced coagulation assays are thrombin generation and measurements of specific coagulation factors, several of which are vitamin K dependent. Vitamin K is essential in the coagulation system and also involved in many other physiological processes. Deficiency of this vitamin is common, but not well studied in patients undergoing head an neck free flap surgery. The investigators plan to study ROTEM and other above mentioned coagulation parameters in patients undergoing major head and neck surgery including microvascular free flap reconstruction to assess if these parameters can help predict patients at risk for bleeding or flap thrombosis. Further on this could hopefully enable prevention of complications and improve treatment of coagulation complications that still occur.

Description:

Microvascular reconstructive free flap surgery is an important part of the recommended treatment for extensive head and neck tumors. However, the procedure includes risks of perioperative coagulation related complications, such as bleeding, but also thrombosis in the flap blood vessels. In about 10% of cases this requires reoperation, but, in spite of intense efforts, about 5% of all patients suffer from flap failure, i.e. necrosis of the free flap. This results in significant suffering for the patients who must undergo further surgery and oftentimes considerable prolonged hospital stay etc. This in turn leads to increased health care costs. There are several indications that tendency towards thrombosis can increase the risk of flap failure. Previous studies have indicated that increased levels of fibrinogen and inherited thrombophilia, such as APC resistance, are associated with thrombotic free flap complications, but more conventional coagulation parameters, such as PK/INR and aPTT have not shown the same connection. Low fibrinogen levels have also been associated with bleeding complications. Most patients undergoing the above mentioned surgery receive anticoagulant therapy. However, there is no international consensus on any specific pharmacological regime. Many different prophylactic therapies are used, including low molecular weight heparin, dextran and acetylsalicylic acid. Still coagulation-related complications are difficult to prevent. Defective coagulation apparently seems to be associated with bleeding and thrombotic perioperative complications. It would therefore be desirable to increase the knowledge about factors influencing the development of these complications, and the patients at risk for them. ROTEM, rotational thromboelastometry, is a viscoelastic essay that provides a more global view of the hemostatic potential in whole blood, and it is also one of few more advanced assays that can be analyzed around the clock in many Swedish hospitals. The aim of this project is to study perioperative coagulation and vitamin K status, and thereby further on hopefully be able to prevent, and improve the treatment of, bleeding and thrombosis related complications in patients undergoing head and neck microvascular free flap surgery.

Recruitment information / eligibility
Status	Completed
Enrollment	40
Est. completion date	October 1, 2021
Est. primary completion date	September 15, 2021
Accepts healthy volunteers	No
Gender	All
Age group	18 Years and older
Eligibility	Inclusion Criteria: - Patients undergoing head and neck surgery including resection and reconstruction with a microvascular free flap at Skåne University Hospital in Lund, Sweden, who accept participation in the study. Exclusion Criteria: - Age under 18 years. - Inability to understand information or make an informed choice about participation. - Hospitalization > 24 h prior to primary surgery.

Study Design

Related Conditions & MeSH terms

Locations
Country	Name	City	State
Sweden	Region Skåne	Lund	Skåne

Sponsors *(1)*
Lead Sponsor	Collaborator
Region Skane

Country where clinical trial is conducted

Sweden,

References & Publications (7)

Cervenka B, Bewley AF. Free flap monitoring: a review of the recent literature. Curr Opin Otolaryngol Head Neck Surg. 2015 Oct;23(5):393-8. doi: 10.1097/MOO.0000000000000189. — View Citation

Copelli C, Tewfik K, Cassano L, Pederneschi N, Catanzaro S, Manfuso A, Cocchi R. Management of free flap failure in head and neck surgery. Acta Otorhinolaryngol Ital. 2017 Oct;37(5):387-392. doi: 10.14639/0392-100X-1376. — View Citation

Handschel J, Burghardt S, Naujoks C, Kubler NR, Giers G. Parameters predicting complications in flap surgery. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 May;115(5):589-94. doi: 10.1016/j.oooo.2012.09.007. Epub 2012 Dec 12. — View Citation

Kolbenschlag J, Daigeler A, Lauer S, Wittenberg G, Fischer S, Kapalschinski N, Lehnhardt M, Goertz O. Can rotational thromboelastometry predict thrombotic complications in reconstructive microsurgery? Microsurgery. 2014 May;34(4):253-60. doi: 10.1002/micr.22199. Epub 2013 Oct 21. — View Citation

Kolbenschlag J, Diehm Y, Daigeler A, Kampa D, Fischer S, Kapalschinski N, Goertz O, Lehnhardt M. Insufficient fibrinogen response following free flap surgery is associated with bleeding complications. GMS Interdiscip Plast Reconstr Surg DGPW. 2016 Nov 22;5:Doc22. doi: 10.3205/iprs000101. eCollection 2016. — View Citation

Lison S, Weiss G, Spannagl M, Heindl B. Postoperative changes in procoagulant factors after major surgery. Blood Coagul Fibrinolysis. 2011 Apr;22(3):190-6. doi: 10.1097/MBC.0b013e328343f7be. — View Citation

Zhou W, Zhang WB, Yu Y, Wang Y, Mao C, Guo CB, Yu GY, Peng X. Are antithrombotic agents necessary for head and neck microvascular surgery? Int J Oral Maxillofac Surg. 2019 Jul;48(7):869-874. doi: 10.1016/j.ijom.2018.10.022. Epub 2018 Nov 26. — View Citation

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Coagulation and Vitamin K in Head and Neck Microvascular Free Flap Surgery

Clinical Trial Details — Status: Completed

Administrative data

Study information

Clinical Trial Summary

Description:

Recruitment information / eligibility

Study Design

Related Conditions & MeSH terms

Locations

Sponsors (1)

Country where clinical trial is conducted

References & Publications (7)

Outcome

Type	Measure	Description	Time frame
Primary	Perioperative changes in ROTEM MCF EXTEM	Perioperative changes in ROTEM MCF (EXTEM). Baseline values measured at start of surgery (day 0), thereafter repeated measurements are made until day 6. Power calculation is based on an expected change in ROTEM MCF (EXTEM) from day 0 to postoperative day 2 (based on Lison et al, Blood Coagul Fibrinolysis. 2011.).	Day 0 to day 6
Secondary	Perioperative changes in ROTEM Clotting time	Perioperative changes in ROTEM Clotting Time (CT, s). Baseline values measured at start of surgery (day 0), thereafter repeated measurements are made until day 6.	Day 0 to day 6
Secondary	Perioperative changes in ROTEM Clot Formation Time	Perioperative changes in ROTEM Clot Formation Time (CFT, s).	Day 0 to day 6
Secondary	Perioperative changes in ROTEM alpha angle	Perioperative changes in ROTEM alpha angle (°).	Day 0 to day 6
Secondary	Perioperative changes in ROTEM Lysis Index 60	Perioperative changes in ROTEM Lysis Index 60 (LI60, %).	Day 0 to day 6
Secondary	Perioperative changes in ROTEM Maximum Clot Firmness	Perioperative changes in ROTEM Maximum Clot Firmness (mm).	Day 0 to day 6
Secondary	Perioperative changes in prothrombin time	Perioperative changes in prothrombin time (INR).	Day 0 to day 6
Secondary	Perioperative changes in activated partial thromboplastin time	Perioperative changes in activated partial thromboplastin time (APTT, s).	Day 0 to day 6
Secondary	Perioperative changes in thrombocyte levels	Perioperative changes in thrombocyte levels (number/L).	Day 0 to day 6
Secondary	Perioperative changes in thrombin generation; lag time	Perioperative changes in thrombin generation; lag time (s).	Day 0 to day 6
Secondary	Perioperative changes in thrombin generation; peak thrombin	Perioperative changes in thrombin generation; peak thrombin (nM).	Day 0 to day 6
Secondary	Perioperative changes in thrombin generation; area under the curve	Perioperative changes in thrombin generation; area under the curve (AUC).	Day 0 to day 6
Secondary	Perioperative changes in specific coagulation factors; protein C (kIU/L)	Perioperative changes in protein C (kIU/L).	Day 0 to day 6
Secondary	Perioperative changes in specific coagulation factors; protein S	Perioperative changes in protein S (kIU/L).	Day 0 to day 6
Secondary	Perioperative changes in specific coagulation factors; fibrinogen	Perioperative changes in fibrinogen (g/L).	Day 0 to day 6
Secondary	Perioperative changes in specific coagulation factors; antithrombin	Perioperative changes in antithrombin (kIU/L).	Day 0 to day 6
Secondary	Perioperative changes in fibrinolytic activation	Perioperative changes in plasmin-antiplasmin complex, PAP (µg/L).	Day 0 to day 6
Secondary	Perioperative changes in the vitamin K-dependent protein Gas6	Perioperative changes in the vitamin K-dependent protein Gas6 (ng/mL).	Day 0 to day 6
Secondary	Perioperative changes in the vitamin K-dependent protein dp-uc-MGP	Perioperative changes in the vitamin K-dependent protein dp-uc-MGP (pM/L).	Day 0 to day 6
Secondary	Perioperative changes in the vitamin K-dependent protein Axl-receptor	Perioperative changes in the vitamin K-dependent protein Axl-receptor (pg/mL).	Day 0 to day 6
Secondary	Perioperative changes in the vitamin K-dependent protein PIVKA-II	Perioperative changes in the vitamin K-dependent protein PIVKA-II (mAU/mL).	Day 0 to day 6
Secondary	Coagulation related complications	Connection between perioperative complications (thrombotic [arterial/venous] or bleeding) in the surgical site and abnormal levels of coagulation parameters mentioned above.	Day 0 until end of hospital stay or a at the latest day 30 days after the primary operation.
Secondary	Perioperative changes in ROTEM FIBTEM Maximum Clot Firmness	Perioperative changes in ROTEM INTEM Maximum Clot Firmness (MCF, mm).	Day 0 to day 6
Secondary	Perioperative changes in ROTEM INTEM Clotting Time	Perioperative changes in ROTEM INTEM Clotting Time (CT, s).	Day 0 to day 6