Study Of Weight-Based Versus Standard Dose Enoxaparin Thromboprophylaxis In High-Risk Hospitalized Cancer Patients

A Randomized, Phase II Study Of Weight-Based Versus Standard Dose Enoxaparin Thromboprophylaxis In High-Risk Hospitalized Cancer Patients

Hospitalized patients with histologically or cytologically confirmed diagnosis of solid tumor malignancy, lymphoma, or multiple myeloma and who are at high risk for a venous thromboembolism will be randomized to standard dose versus intermediate dose enoxaparin.

Study Overview

• Status: Completed
• Conditions: Venous Thormboembolism
• Intervention / Treatment: Drug: Enoxaparin

Detailed Description

In a phase II trial, high risk hospitalized cancer patients will be enrolled and randomized to standard dose enoxaparin versus intermediate dose (weight adjusted) enoxaparin thromboprophylaxis. Study subjects will be administered enoxaparin during hospitalization in a double-blinded manner. Following completion of 14 days, the study arms will be unblinded and lower extremity ultrasound performed on the standard dose enoxaparin arm in order to more accurately determine the overall cumulative incidence of thrombosis in this group.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation

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:

• Participants must have histologically or cytologically confirmed diagnosis of solid tumor malignancy, lymphoma or multiple myeloma.
• Cancer diagnosis or received treatment (chemotherapy or radiotherapy) for malignancy within the previous 6 months

• One or more Padua-based risk factor:

  • History of previous venous thromboembolic event (excluding superficial vein thrombosis)
  • Reduced mobility (ECOG performance status 3 or 4, see Appendix A)
  • Established hereditary thrombophilia (e.g. Factor V Leiden, G20210 prothrombin mutation, protein C or S deficiency, antithrombin deficiency).
  • Recent surgery within the last 30 days
  • Age ≥ 70 years
  • Congestive heart failure (NYHA class III or IV)
  • Complicated respiratory insufficiency (defined as an increased requirement for supplementary oxygen of at least 2L)
  • Acute myocardial infarction or ischemic stroke
  • Obesity (BMI ≥ 30)
  • Receiving hormonal agents (e.g. tamoxifen, estrogen, testosterone)
  • Acute infection (i.e. requiring antimicrobial therapy)
• Age ≥ 18 years
• Life expectancy of greater than 30 days
• Platelet count ≥ 100,000/mcL
• Creatinine < 1.5 mg/dL or estimated creatinine clearance ≥ 50 mL/min/1.73 m2
• Ability to understand and the willingness to sign a written informed consent document
• Weight between 50kg to 130 kg.

Exclusion Criteria:

• History of allergic reactions attributed to heparin or low molecular weight heparin
• Active bleeding or otherwise considered high risk for hemorrhage (e.g. known acute gastrointestinal ulcer)
• Any history of significant hemorrhage (requiring hospitalization or transfusion) within the last 6 months (excluding hemorrhage during operative procedure).
• History of heparin induced Thrombocytopenia
• Presence of coagulopathy (PT or PTT> 1.2 x upper limit of normal)
• Known diagnosis of disseminated intravascular coagulation
• Currently receiving therapeutic anticoagulant therapy or dual antiplatelet therapy (eg. aspirin and clopidogrel)
• Uncontrolled arterial hypertension (systolic blood pressure > 200mmHg, diastolic >110mmHg)
• Active peptic ulcer disease
• Bacterial Endocardititis
• Received any type of Pharmacologic Thromboprophylaxis (e.g. low molecular weight heparin or heparin) for >48 hours during current hospitalization
• Known brain metastases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A: Standard Dose Enoxaparin; Participants will receive Enoxaparin 40 mg subcutaneously once daily. On study Enoxaparin will be administered for up 14 days during hospitalization. After the day 14 assessment, treatment arms will be un-blinded in order to appropriately schedule a bilateral lower extremity ultrasound for participants enrolled onto Arm A at day 17.	Drug: Enoxaparin; Other Names: Lovenox
Active Comparator: B: Weight Adjusted Enoxaparin; Participants will receive Enoxaparin at 1mg/kg subcutaneously once daily with maximum dose of 100 mg daily. Participants who weigh more than 100kg will be capped at 100mg. On study Enoxaparin will be administered for up 14 days during hospitalization.	Drug: Enoxaparin; Other Names: Lovenox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Number of Venous Thromboembolic Events (VTE) in Standard Dose Enoxaparin Arm at 17 Days	To investigate the numbers of VTE in hospitalized cancer patients receiving standard dose	17 days only measured in Arm A (Standard dose enoxaparin)
Number Participants With Major Hemorrhage	Number of major hemorrhage in weight-adjusted enoxaparin arm and standard-dose enoxaparin arm	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Symptomatic Venous Thromboembolic Events (VTE)	Comparing number of symptomatic VTE (data collected prior to unblinding) for the standard dose (Arm A) versus intermediate dose enoxaparin (Arm B).	14 days

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Jeffrey Zwicker, MD, Beth Israel Deaconess Medical Center

Publications and helpful links

General Publications

• Zwicker JI, Roopkumar J, Puligandla M, Schlechter BL, Sharda AV, Peereboom D, Joyce R, Bockorny B, Neuberg D, Bauer KA, Khorana AA. Dose-adjusted enoxaparin thromboprophylaxis in hospitalized cancer patients: a randomized, double-blinded multicenter phase 2 trial. Blood Adv. 2020 May 26;4(10):2254-2260. doi: 10.1182/bloodadvances.2020001804.

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): December 7, 2020
• Study Completion (Actual): June 7, 2021

Study Registration Dates

• First Submitted: March 3, 2016
• First Submitted That Met QC Criteria: March 7, 2016
• First Posted (Estimate): March 11, 2016

Study Record Updates

• Last Update Posted (Actual): July 8, 2021
• Last Update Submitted That Met QC Criteria: July 6, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Enoxaparin
• Other Study ID Numbers: 15-547

Plan for Individual participant data (IPD)

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