Effect of Vitamin K in Critically Ill Patients (VITAKOAG)

Effect of Vitamin K in Critically Ill Patients With Spontaneously Increased Pro-thrombin Time Measured With Routine Coagulation Tests and Advanced Coagulation- and Vitamin K-assays

Critically ill patients with spontaneously prolonged pro-thrombin time, where administration of intravenous administration of phytomenadione (vitamin K) has been ordered by the treating physician will be identified. After signed informed consent baseline samples will be collected. Phytomenadione will be given and 24 hours after administration new blood samples will be collected. Several different advanced coagulation and vitamin K-assays will be performed before and 24 hours after vitamin K administration.

Study Overview

• Status: Completed
• Conditions: Coagulopathy, Consumption; Coagulation Factor Deficiency; Vitamin K Deficiency
• Intervention / Treatment: Drug: Phytomenadione

Detailed Description

Vitamin K-deficiency is common in the peri-operative and intensive care setting. It is often seen in patients with prolonged prothrombin complex (PK-INR). A prolonged (PK-INR) is sometimes treated with intravenous vitamin K, even in non-warfarin treated or non-liver failure patients. Despite the development of this practice the knowledge about how intravenously given vitamin K affects routine coagulation status and other advanced laboratory coagulations assays is rare.

The aim of this study is to investigate the effects of intravenously administered vitamin K on routine coagulation status and on advanced coagulation and vitamin K-assays in post-operative- and critically ill patients with prolonged PK-INR.

Patients with spontaneously prolonged PK-INR are routinely given intravenous vitamin K but it is largely unknown how this procedure affects the included coagulation assays. This research project may contribute to increased knowledge concerning effects of intravenously given vitamin K in critical ill patients with spontaneous coagulopathies. Since spontaneous coagulopathy is frequently occurring in critically ill and postoperative patients due to various underlying conditions and current evidence for vitamin K administration is based on scarce evidence more research in this area is motivated.

• Study Type: Observational
• Enrollment (Actual): 52

Contacts and Locations

Study Locations

• Sweden
  • Skåne
    • Lund, Skåne, Sweden, 22185
      • Intensive and Perioperative Care. Skåne University Hospital. Lund
    • Lund, Skåne, Sweden, 22185
      • Skåne University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Critically ill patients at the postoperative care unit or at the intensive care unit with a prothrombin complex (PK-INR) > 1.2 during office hours who are ordered parenteral phytomenadione 10 mg will be eligible for inclusion

Description

Inclusion Criteria:

• Critically ill patients at the postoperative care unit or at the intensive care unit with a prothrombin complex (PK-INR) > 1.2 during office hours who are ordered parenteral phytomenadione 10 mg will be eligible for inclusion

Exclusion Criteria:

• Warfarin treatment
• Treatment with novel oral anticoagulants
• Hepatocellular carcinoma
• Liver resection within 6 months
• Known pre-existing coagulopathy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with increased PK-INR; Critically ill patients with spontaneously increased prothrombin complex (PK-INR) who are given phytomenadione intravenously at the discretion of the treating physician	Drug: Phytomenadione; Blood samples will be taken before and after intravenously prescribed phytomenadione is given. Phytomenadione will be given independently of this study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in prothrombin complex (PK-INR)	Prothrombin complex (PK-INR) with Owren and Quick reagents	Before and 24 hours after given phytomenadione

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in concentration of coagulation factors II, VII, IX and X in plasma		Before and 24 hours after given phytomenadione
Change in concentration of PIVKA-II in plasma	Protein Induced by Vitamin K Absence or antagonism for factor II (PIVKA-II)	Before and 24 hours after given phytomenadione
Change in concentration of protein C and S in plasma		Before and 24 hours after given phytomenadione
Change in concentration of dp-ucMGP in plasma	Dephospho-uncarboxylated Matrix Gla Protein (dp-ucMGP)	Before and 24 hours after given phytomenadione
Change in thrombin generation assay in plasma		Before and 24 hours after given phytomenadione
Change in thromboelastometry assay in whole blood	Thromboelastometry using ROTEM with tissue factor activation (EXTEM reagent)	Before and 24 hours after given phytomenadione

Collaborators and Investigators

• Sponsor: Region Skane

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 13, 2019
• Primary Completion (ACTUAL): March 20, 2020
• Study Completion (ACTUAL): March 20, 2020

Study Registration Dates

• First Submitted: December 18, 2018
• First Submitted That Met QC Criteria: December 19, 2018
• First Posted (ACTUAL): December 20, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 18, 2021
• Last Update Submitted That Met QC Criteria: March 16, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Nutrition Disorders; Hemorrhagic Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Blood Coagulation Disorders; Thrombophilia; Disseminated Intravascular Coagulation; Vitamin K Deficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Micronutrients; Vitamins; Antifibrinolytic Agents; Hemostatics; Coagulants; Vitamin K 1
• Other Study ID Numbers: VITAKOAG

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No