Thromboprophylaxis in Oesophageal Cancer Patients (TOP-RCT)

Thromboprophylaxis in Oesophageal Cancer Patients - A Randomized, Controlled Trial

The purpose of the study is to examine the efficacy and safety of prolonged thromboprophylactic treatment with Fragmin® in oesophageal cancer patients undergoing intended curative surgery.

Study Overview

• Status: Recruiting
• Conditions: Thrombosis; Esophageal Neoplasms; Thromboembolism
• Intervention / Treatment: Drug: Fragmin 5000 UNT in 0.2 ML Prefilled Syringe

Detailed Description

Hypotheses

1. The intervention group of oesophageal cancer patients, who receive prolonged thromboprophylaxis with Fragmin® has a lower VTE risk, expressed by a lower prothrombin fragment F1+2, 30 days after surgery than the control group, who receive Fragmin® for 10 days.
2. The intervention group does not demonstrate an increased bleeding tendency compared with the control group.

Primary endpoint The primary endpoint is the difference in prothrombin fragment F1+2 30 days after surgery between the intervention and the control group.

Secondary and safety endpoints The secondary endpoints are incidence of bleeding, VTE and mortality 30 days and one year after surgery.

Study design

The study is comprised of three specific objectives, presented in three work packages (WP):

• WP1: Randomization of 100 oesophageal cancer patients undergoing intended curative surgery to either a 10 or 30-day prophylactic LMWH-regime.
• WP2: Investigation of the coagulation in the WP1 population. The aim is to substantially improve understanding of the coagulation pathophysiology and the mechanisms behind the increased thromboembolic risk in oesophageal cancer patients.
• WP3: The lectin pathway complement proteins are suspected to play a role in the increased risk of thrombosis in cancer. We aim to examine this further by measuring complement protein levels in the WP1 population and investigate if there is a correlation between complement levels and changes in the coagulation.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Anne-Mette Hvas, MD; Phone Number: 004578455252; Email: annehvas@rm.dk
• Study Contact Backup: Name: Tua Gyldenholm, MD; Phone Number: 004525136781; Email: tuagyl@clin.au.dk

Study Locations

• Denmark
  • Aarhus N, Denmark, 8000
    • Recruiting
    • Thrombosis and Haemostasis Research Unit, Department for Clinical Biochemistry, Aarhus University Hospital
    • Contact: Anne-Mette Hvas, MD, Ph.D.; Phone Number: +45 2334 8252; Email: annehvas@rm.dk
    • Principal Investigator: Anne-Mette Hvas, MD, Ph.D.
    • Sub-Investigator: Tua Gyldenholm, MD
    • Sub-Investigator: Thomas Decker Christensen, MD, PhD, DMSci
    • Sub-Investigator: Niels Katballe, MD, PhD
    • Sub-Investigator: Daniel W Kjær, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Cancer located in oesophagus and/or cardia.
2. Candidate for intended curative surgery.
3. Age > 18 years.

Exclusion Criteria:

1. Known inherited bleeding disorder.
2. Unable to provide informed consent.
3. Arterial or venous thromboembolic events within the last three months.
4. On-going anticoagulant treatment (Vitamin K antagonists or direct oral anticoagulants).
5. Pregnant or has given birth within the last three months.
6. Known allergy to the trial drug Dalteparin (Fragmin®).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Intervention group (n=50, anticipated) receives 30 days postoperative treatment with 5000 IE LMWH daily.	Drug: Fragmin 5000 UNT in 0.2 ML Prefilled Syringe; 30 days postoperative prophylactic treatment.; Other Names: Low Molecular Weight Heparin
Active Comparator: Control; Control group (n=50, anticipated) receives standard 10 days postoperative treatment with 5000 IE LMWH daily.	Drug: Fragmin 5000 UNT in 0.2 ML Prefilled Syringe; 30 days postoperative prophylactic treatment.; Other Names: Low Molecular Weight Heparin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prothrombin fragment F1+2	Difference in prothrombin fragment F1+2 between the intervention and the control group.	30 days after surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding	Incidence of bleeding	30 days after surgery.
Venous thromboembolic events	Incidence of venous thromboembolic events	30 days and one year after surgery
Mortality	Mortality	30 days and one year after surgery

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital
• Investigators: Principal Investigator: Anne-Mette Hvas, MD, University of Aarhus

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2021
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: September 23, 2021
• First Submitted That Met QC Criteria: September 23, 2021
• First Posted (Actual): October 5, 2021

Study Record Updates

• Last Update Posted (Actual): October 5, 2021
• Last Update Submitted That Met QC Criteria: September 23, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Esophageal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Embolism and Thrombosis; Esophageal Diseases; Thrombosis; Thromboembolism; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin
• Other Study ID Numbers: 2021-001335-24

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
• product manufactured in and exported from the U.S.: No