search
Back to results

WAVe Study - Weight Adjusted Dalteparin for Patients Over 90 kg With Acute Cancer Associated Venous Thromboembolism (WAVe)

Primary Purpose

Cancer, Venous Thromboembolism, Obesity

Status
Recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Dalteparin
Sponsored by
Ottawa Hospital Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer focused on measuring Dalteparin, Fragmin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Known pathologically-confirmed cancer (other than basal-cell or squamous-cell carcinoma of the skin),
  2. Confirmed symptomatic or incidental deep vein thrombosis requiring treatment, or confirmed symptomatic or incidental pulmonary embolism of a segmental or larger pulmonary artery,
  3. Weight > 90 kg,
  4. Age ≥18 years,
  5. Hemoglobin ≥ 80 g/L,
  6. Able and willing to comply with study procedures and follow-up examinations contained within the written consent form.

Exclusion Criteria:

  1. Acute VTE managed with thrombectomy, insertion of an inferior vena cava filter or with the use of thrombolytic agents,
  2. More than 72 hours pre-treatment with therapeutic dosage of other LMWH, direct oral anticoagulants or vitamin K antagonists prior to enrolment to manage the current VTE event (unless the participant has been treated with weight-adjusted doses of commercial dalteparin in consistency with the dosing regime outlined in the protocol up to Day 7 visit [±2 days]),
  3. Contraindication to heparin therapy:

    1. history of heparin induced thrombocytopenia (HIT) as reported by patient,
    2. platelet count of less than 50 x 109/L,
    3. actively bleeding,
    4. reported history of severe uncontrolled hypertension,
    5. documented peptic ulcer within 6 weeks,
    6. reported history of severe hepatic failure,
    7. creatinine clearance of < 30 ml/min as calculated by the Cockcroft-Gault formula,
    8. heparin allergy,
    9. Other contraindication to anticoagulation.
  4. An Eastern Cooperative Oncology Group (ECOG) Performance Status of 3 or 4 at the time of study enrolment,
  5. Life expectancy < 1 month,
  6. Women of childbearing age without proper contraceptive measures and women who are pregnant or breast feeding,
  7. Participating in another interventional trial that may result in co-intervention or contamination (to be determined by sponsor),
  8. Unable/unwilling to provide informed consent.

Sites / Locations

  • Alberta Health ServicesRecruiting
  • Nova Scotia Health AuthorityRecruiting
  • Juravinski HospitalRecruiting
  • The Ottawa HospitalRecruiting
  • Toronto General HopsitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Weight adjusted dalteparin

Arm Description

Participants will receive a daily subcutaneous injection of weight-adjusted dalteparin (See Table below) at a dose of approx. 200 IU/kg beginning on the day of enrolment and for a one month. 91 to 95 kg: 18,000 IU daily ( or 1 prefilled syringe of 18,000 IU) 96 to 105 kg: 20,000 IU daily ( or 2 prefilled syringes of 10,000 IU) 106 to 120 kg: 22,500 IU daily ( or 2 pre-filled syringes (10,000 and 12,500 IU)) 121 to 130 kg: 25,000 IU daily ( or 2 prefilled syringes of 12,500 IU) 131 to 145 kg: 27,500 IU daily ( or 2 pre-filled syringes (12,500 and 15,000 IU)) 146 to 150 kg: 30,000 IU daily ( or 2 prefilled syringes of 15,000 IU) ≥ 151 kg: 33,000 IU daily ( or 2 prefilled syringes (15,000 and 18,000 IU))

Outcomes

Primary Outcome Measures

Major bleeding episode
Fatal bleeding, and/or, Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or, Bleeding causing a fall in hemoglobin level of ≥20 g/L, or leading to transfusion of ≥2 units of whole blood or red cells.

Secondary Outcome Measures

Clinically relevant non major bleeding events
As overt bleeding episodes not meeting the inclusion for major bleeding but associated with one of the following: Medical intervention, An unscheduled contact with a physician, Temporary cessation of anticoagulant treatment.
Minor bleeding events
Overt bleeding not meeting the major bleeding or clinically-relevant non-major bleeding definitions
Recurrent VTE events
Recurrent deep vein thrombosis Recurrent Pulmonary embolism
Overall mortality
Death
Bioaccumulation of study drug
Trough anti-Xa levels measured at Day 7 and Day 30 follow-up visits will be generated for the once and twice-daily dosing regimen

Full Information

First Posted
September 26, 2017
Last Updated
March 16, 2023
Sponsor
Ottawa Hospital Research Institute
Collaborators
Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network
search

1. Study Identification

Unique Protocol Identification Number
NCT03297359
Brief Title
WAVe Study - Weight Adjusted Dalteparin for Patients Over 90 kg With Acute Cancer Associated Venous Thromboembolism
Acronym
WAVe
Official Title
A Multicentre Prospective Cohort Study Assessing the Use of Weight-Adjusted Low-Molecular-Weight-Heparin in Patients Over 90 kg With Acute Cancer-Associated Venous Thromboembolism
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 21, 2018 (Actual)
Primary Completion Date
June 30, 2023 (Anticipated)
Study Completion Date
June 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Hospital Research Institute
Collaborators
Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Cancer patients that develop blood clots are treated with low molecular weight heparin injections (LMWH). One kind of these LMWHs, dalteparin, has its dose determined based on a patient's weight using a formula of 200 international units (IU) per kilogram (kg). The current dosing of dalteparin approved by Health Canada has a maximum daily dose of 18 000 IU/day which is weight-adjusted for patients up to 90 kg. Any patient weighing more than 90 kg would take the same dosage regardless of their weight. The aim of this study is to assess the safety of using weight-adjusted dalteparin in cancer-associated venous thromboembolism patients that weigh more than 90 kg.
Detailed Description
The study is designed as a multicentre prospective cohort study with multiple Canadian sites. It will be initiated at The Ottawa Hospital prior to being offered externally. After obtaining informed consent, and confirming eligibility, participants weighing more than 90 kg with acute cancer-associated thrombosis will be treated with therapeutic weight-adjusted dalteparin (subcutaneous once daily injection, or twice daily, if the conditions of the participant do not allow once daily injection as per clinical judgement) beginning at enrolment (within 12 hours) and continuing until Day 30 visit. Subjects will receive therapeutic doses of dalteparin at a dose of approximately 200 IU/kg SC daily (up to 33,000 IU) for one month. Following this study period of 30 days (± 4 days), patients will be followed for 5 months. During the follow-up period, each patient will pursue his/her treatment as per usual standard treatment protocols provided at each institution. Treatment used and clinical outcomes will be collected at the end of the follow-up period. The majority of Canadian Thrombosis specialists use weight adjusted dosing of dalteparin in patients weighing more than 90 kg with cancer-associated VTE. No expert recommends capping the dose of dalteparin to 18,000 IU in patients weighing over 90 kg as suggested by the product monograph. However, the risk of major bleeding episodes in patients over 90 kg receiving weight-adjusted LMWH remains unclear. The estimated rate of major bleeding episodes of patients with cancer associated VTE (Mean weight 79.1 kg) managed with therapeutic dose of dalteparin is 3.6% (95% CI: 1.9 to 6.2). We hypothesize that the rate of major bleeding events will be similar in patients (> 90 kg) with cancer-associated VTE treated with dalteparin 200 IU/kg daily (up to 33,000 IU). We plan to recruit 150 patients in this cohort study. We expect 6 major bleeding events. This would provide us with an overall bleeding event of 4% with an upper bound of the confidence interval of 8.5%). An informal survey of Canadian thrombosis expert has demonstrated that clinicians would feel reassured and continue to use weight-adjusted dalteparin in cancer patients weighing more than 90kg if the upper bound of the 95% confidence interval is less than 9% (i.e. < 3% possible absolute rate difference).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer, Venous Thromboembolism, Obesity
Keywords
Dalteparin, Fragmin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Weight adjusted dalteparin
Arm Type
Experimental
Arm Description
Participants will receive a daily subcutaneous injection of weight-adjusted dalteparin (See Table below) at a dose of approx. 200 IU/kg beginning on the day of enrolment and for a one month. 91 to 95 kg: 18,000 IU daily ( or 1 prefilled syringe of 18,000 IU) 96 to 105 kg: 20,000 IU daily ( or 2 prefilled syringes of 10,000 IU) 106 to 120 kg: 22,500 IU daily ( or 2 pre-filled syringes (10,000 and 12,500 IU)) 121 to 130 kg: 25,000 IU daily ( or 2 prefilled syringes of 12,500 IU) 131 to 145 kg: 27,500 IU daily ( or 2 pre-filled syringes (12,500 and 15,000 IU)) 146 to 150 kg: 30,000 IU daily ( or 2 prefilled syringes of 15,000 IU) ≥ 151 kg: 33,000 IU daily ( or 2 prefilled syringes (15,000 and 18,000 IU))
Intervention Type
Biological
Intervention Name(s)
Dalteparin
Intervention Description
daily subcutaneous injection of weight-adjusted dalteparin
Primary Outcome Measure Information:
Title
Major bleeding episode
Description
Fatal bleeding, and/or, Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or, Bleeding causing a fall in hemoglobin level of ≥20 g/L, or leading to transfusion of ≥2 units of whole blood or red cells.
Time Frame
up to day 30
Secondary Outcome Measure Information:
Title
Clinically relevant non major bleeding events
Description
As overt bleeding episodes not meeting the inclusion for major bleeding but associated with one of the following: Medical intervention, An unscheduled contact with a physician, Temporary cessation of anticoagulant treatment.
Time Frame
up to day 30
Title
Minor bleeding events
Description
Overt bleeding not meeting the major bleeding or clinically-relevant non-major bleeding definitions
Time Frame
up to day 30
Title
Recurrent VTE events
Description
Recurrent deep vein thrombosis Recurrent Pulmonary embolism
Time Frame
Up to day 180
Title
Overall mortality
Description
Death
Time Frame
Up to day 180
Title
Bioaccumulation of study drug
Description
Trough anti-Xa levels measured at Day 7 and Day 30 follow-up visits will be generated for the once and twice-daily dosing regimen
Time Frame
Up to day 30

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Known pathologically-confirmed cancer (other than basal-cell or squamous-cell carcinoma of the skin), Confirmed symptomatic or incidental deep vein thrombosis requiring treatment, or confirmed symptomatic or incidental pulmonary embolism of a segmental or larger pulmonary artery, Weight > 90 kg, Age ≥18 years, Hemoglobin ≥ 80 g/L, Able and willing to comply with study procedures and follow-up examinations contained within the written consent form. Exclusion Criteria: Acute VTE managed with thrombectomy, insertion of an inferior vena cava filter or with the use of thrombolytic agents, More than 72 hours pre-treatment with therapeutic dosage of other LMWH, direct oral anticoagulants or vitamin K antagonists prior to enrolment to manage the current VTE event (unless the participant has been treated with weight-adjusted doses of commercial dalteparin in consistency with the dosing regime outlined in the protocol up to Day 7 visit [±2 days]), Contraindication to heparin therapy: history of heparin induced thrombocytopenia (HIT) as reported by patient, platelet count of less than 50 x 109/L, actively bleeding, reported history of severe uncontrolled hypertension, documented peptic ulcer within 6 weeks, reported history of severe hepatic failure, creatinine clearance of < 30 ml/min as calculated by the Cockcroft-Gault formula, heparin allergy, Other contraindication to anticoagulation. An Eastern Cooperative Oncology Group (ECOG) Performance Status of 3 or 4 at the time of study enrolment, Life expectancy < 1 month, Women of childbearing age without proper contraceptive measures and women who are pregnant or breast feeding, Participating in another interventional trial that may result in co-intervention or contamination (to be determined by sponsor), Unable/unwilling to provide informed consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Limmy Lobo, MSc
Phone
613-737-8899
Ext
72103
Email
llobo@ohri.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Carrier, MD
Organizational Affiliation
Ottawa Hospital Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Alberta Health Services
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2V2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cynthia Wu, MD, FRCPC
Facility Name
Nova Scotia Health Authority
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 1V7
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sudeep Shivakumar, MD, FRCPC
Facility Name
Juravinski Hospital
City
Hamilton
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Gross, MD, FRCPC
Facility Name
The Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yan He, MSc
First Name & Middle Initial & Last Name & Degree
Marc Carrier, MD, FRCPC
Facility Name
Toronto General Hopsital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1J6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Erik Yeo, MD, FRCPC

12. IPD Sharing Statement

Learn more about this trial

WAVe Study - Weight Adjusted Dalteparin for Patients Over 90 kg With Acute Cancer Associated Venous Thromboembolism

We'll reach out to this number within 24 hrs