Management of Recurrent Venous Thromboembolism During Anticoagulant Treatment in Cancer Patients - a Prospective Cohort Study (REDUCE)

Objective: To prospectively evaluate clinical outcomes during guideline-recommended LMWH dose escalation for recurrent VTE during LMWH or DOAC treatment for cancer-associated thrombosis.

Study design: International, prospective, observational cohort study Study population: Adult cancer patients with symptomatic or incidental recurrent VTE while receiving LMWH or DOACs for acute VTE are eligible. Main exclusion criteria include anticoagulant treatment for the recurrent VTE for more than 72 hours, severe hepatic dysfunction, active bleeding, recent major surgery, uncontrolled hypertension, known bleeding diathesis, and a life expectancy of less than 1 month.

Study procedures: Patients will be managed at the discretion of the treating physician, who will be encouraged to follow guideline recommendations. These guidelines suggest supra-therapeutic dose LMWH for 4 weeks (+/- 5 days) followed by therapeutic dose LMWH or therapeutic dose DOAC, while it is suggested to treat patients with VTE recurrence during maintenance dose LMWH (i.e. 75 to 80% of full therapeutic weight adjusted dose) with therapeutic dose of LMWH or DOAC.

Main study parameters/endpoints: The co-primary outcomes are new symptomatic or incidental recurrent VTE during 3 months of follow-up and on-treatment major bleeding. Secondary outcomes include recurrent incidental VTE, recurrent symptomatic VTE, recurrent incidental or symptomatic proximal or distal DVT, recurrent incidental or symptomatic PE, clinically relevant non-major bleeding, all-cause mortality, and cancer-related mortality. VTE occurring at other sites such as cerebral DVT or splanchnic DVT will also be recorded.

Study Overview

• Status: Recruiting
• Conditions: Recurrence; Cancer; Venous Thromboembolism

• Study Type: Observational
• Enrollment (Estimated): 220

Contacts and Locations

• Study Contact: Name: Floris Bosch, Drs.; Phone Number: 0031 20 5668791; Email: f.t.bosch@amsterdamumc.nl
• Study Contact Backup: Name: Marcello Di Nisio, Dr.; Email: mdinisio@unich.it

Study Locations

• Italy
  • Chieti, Italy
    • Recruiting
    • Gabriele D'Annunzio University
    • Contact: Marcello Di Nisio
• Netherlands
  • Amersfoort, Netherlands
    • Recruiting
    • Meander Medisch Centrum
    • Contact: Hans-Martin Otten
  • Amsterdam, Netherlands
    • Recruiting
    • Amsterdam UMC, location AMC
    • Contact: Floris Bosch
  • Leiden, Netherlands
    • Recruiting
    • Leids Universitair Merisch Centrum
    • Contact: Erik Klok, Dr.
• Spain
  • Cadiz, Spain
    • Recruiting
    • Hospital Universitario Puerto Real
    • Contact: Juan Bosco López-Saez
  • Elche, Spain
    • Recruiting
    • Hospital General Universitario de Elche
    • Contact: Francisco J. Pelegrín Mateo
  • Madrid, Spain
    • Recruiting
    • Clínica Universidad Navarra en Madrid
    • Contact: Pedro Ruiz-Artacho
  • Pamplona, Spain
    • Recruiting
    • Clinica Universidad de Navarra
    • Contact: Sofia Huerga Domínguez
  • Sevilla, Spain
    • Recruiting
    • Hospital Universitario Virgen del Rocio
    • Contact: Luis Jara-Palomares

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Unselected adult cancer patients who develop symptomatic or incidental recurrent VTE while receiving appropriate doses of LMWH or DOACs for an acute VTE.

Description

Inclusion Criteria:

• Documented active cancer (i.e. diagnosis of cancer within the past 6 months; recurrent, regionally advanced, or metastatic disease; currently receiving treatment or received treatment within the past 6 months)
• Objectively confirmed symptomatic or incidental recurrent VTE while on anticoagulant therapy. The previous VTE and index recurrent VTE will include symptomatic or incidentally detected proximal deep vein thrombosis (DVT) of the lower extremities; symptomatic proximal upper extremity DVT (either related to a catheter or not); symptomatic distal DVT; symptomatic or incidentally detected multiple subsegmental, segmental or more proximal pulmonary embolism (PE).

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

• Use of thrombolysis
• Anticoagulant treatment for the recurrent VTE for longer than 72 hours
• Treatment with fondaparinux, unfractionated heparin, prophylactic doses of LMWH, or VKAs at time of recurrent VTE
• Acute hepatitis, chronic active hepatitis, or severe hepatic dysfunction (Child Pugh C or <MELD > 10)
• Active bleeding
• Recent major surgery (<2 weeks or longer, if still at high risk for bleeding)
• Uncontrolled hypertension (systolic arterial pressure >160 mmHg)
• Known bleeding diathesis
• Platelet count <50.000 mm3
• Creatinine clearance <30 mL/min (Cockcroft-Gault formula)
• Life expectancy of less than 1 month
• Dual antiplatelet therapy or aspirin at doses ≥165 mg daily
• Current diagnosis or history of heparin-induced thrombocytopenia
• Any condition, which in the opinion of the investigator, would put the subject at an unacceptable risk from participating in the study.
• Suspected non-compliance at the time of recurrent VTE

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent venous thromboembolism	objectively confirmed recurrent VTE	90 days
Major bleeding	Major bleeding per ISTH criteria	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically relevant non-major bleeding	CRNMB per ISTH criteria	90 days

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: G. d'Annunzio University

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2020
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: January 28, 2022
• First Submitted That Met QC Criteria: January 28, 2022
• First Posted (Actual): February 8, 2022

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Disease Attributes; Embolism and Thrombosis; Recurrence; Thromboembolism; Venous Thromboembolism
• Other Study ID Numbers: W19_237

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Researchers are open to discussing plans for data sharing on IPD analysis.

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