Fondaparinux as Monotherapy for DVT and/or Pulmonary Embolism

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00413504
First received: December 7, 2006
Last updated: February 2, 2009
Last verified: February 2009
  Purpose

To determine whether fondaparinux as monotherapy without warfarin is effective and safe for long-term (90 days) treatment of DVT and/or PE, thus gaining new long-term experience and data using fondaparinux.


Condition Intervention
Deep Vein Thrombosis
Pulmonary Embolism
Drug: Fondaparinux

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Fondaparinux as Monotherapy for Deep Vein Thrombosis and/or Pulmonary Embolism (Pilot Study)

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • Recurrent acute symptomatic DVT confirmed by venous ultrasound and/or CT scan [ Time Frame: 90 Days ]
  • Recurrent acute symptomatic PE confirmed by chest CT scan [ Time Frame: 90 Days ]
  • Major hemorrhage defined as spinal, retroperitoneal or intracranial bleeding, drop in hemoglobin ≥2g/dl or transfusion ≥2U or surgical or medical intervention, death related to bleeding [ Time Frame: 90 Days ]

Secondary Outcome Measures:
  • Comparison of Day Zero, 6 week, and Day 90 platelet counts, renal function, hematocrit and transaminase level [ Time Frame: 90 Days ]

Enrollment: 30
Study Start Date: April 2006
Study Completion Date: July 2007
  Hide Detailed Description

Detailed Description:

Background and Significance:

Warfarin is usually prescribed to manage long-term anticoagulation of deep vein thrombosis (DVT) and pulmonary embolism (PE). However about 5% of patients are unable to tolerate warfarin or to be safely or effectively anticoagulated. Some of the reasons for discontinuing warfarin anticoagulation and switching patients to parenteral anticoagulation are as follows:

  1. Recurrent venous thromboembolism despite anticoagulation with warfarin
  2. Clinically important bleeding complications due to warfarin
  3. Inability to achieve target International Normalized Ratio (INR) on warfarin
  4. Nonbleeding side effects of warfarin, such as hair loss or rash.

These patients who cannot tolerate or respond adequately to warfarin are usually managed with "off-label" twice-daily enoxaparin injections as monotherapy. The approved duration of treatment of DVT and PE with fondaparinux is 5 to 9 days as a "bridge" to warfarin. Until now, no studies have investigated the use of fondaparinux for more than 26 days for the treatment of PE and more than 10 days for the treatment of DVT.

Treatment doses of twice-daily enoxaparin are only Food and Drug Administration (FDA) approved for 5 to 14 days for "bridging" for the treatment of acute DVT and/or PE patients to warfarin.

Fondaparinux is a synthetic antithrombotic agent with specific anti-factor Xa activity. Its pharmacokinetic properties allow for a simple, fixed-dose, once daily regimen of subcutaneous injection, without the need for dose adjustment based on laboratory monitoring.

Fondaparinux is available only in 3 treatment doses and is prescribed once every 24 hours based on patient's weight: 5 mg for patients weighing less than 50 kg, 7.5 mg for patients weighing between 50 to 100 kg, and 10 mg for patients weighing more than 100 kg and is available in prefilled syringes. Also, fondaparinux does not cross react with heparin-induced platelet antibodies, and heparin-induced thrombocytopenia has never been documented with fondaparinux.

The MATISSE Investigators showed that once-daily, subcutaneous administration of fondaparinux for at least 5 days and until 2 consecutive INRs were greater than 2.0 as a "bridge" to warfarin is at least as effective and safe as adjusted-dose, intravenous administration of unfractionated heparin as a "bridge" to warfarin in the initial treatment of hemodynamically stable patients with pulmonary embolism. During the 3-month follow up, 42 of the 1103 patients randomly assigned to receive fondaparinux (3.8 percent) had recurrent thromboembolic events, as compared with 56 of the 1110 patients randomly assigned to receive unfractionated heparin (5.0 percent). Major bleeding occurred in 1.3 percent of the patients treated with fondaparinux and 1.1 percent of those treated with unfractionated heparin. Mortality rates at three months were similar in the two groups.

In another randomized double-blinded trial by the MATISSE Investigators, patients were randomized to fondaparinux once daily versus enoxaparin twice daily for at least 5 days and until 2 consecutive INRs were greater than 2.0 as a "bridge" to warfarin for initial treatment of acute symptomatic DVT. Fondaparinux was found to be as effective and safe as twice-daily enoxaparin during the 3-month follow up period. 43 (3.9%) of 1098 patients randomly assigned to fondaparinux had recurrent thromboembolic events compared with 45 (4.1%) of 1107 patients randomly assigned to enoxaparin. Major bleeding occurred in 1.1% of patients receiving fondaparinux and 1.2% of patients receiving enoxaparin. Mortality rates were 3.8% and 3.0%, respectively.

These two MATISSE trial totaled 4418 patients and led to the FDA approval of fondaparinux in the treatment of acute symptomatic DVT and PE as a "bridge" to warfarin.

In this investigator-initiated trial, we will conduct a cohort study with once daily fondaparinux as monotherapy without warfarin for 90-day management of DVT and/or PE in patients who are unable to tolerate or respond adequately to warfarin.

Research Design and Methods:

This is a cohort study with a sample size of 30 patients at Brigham and Women's Hospital with history of DVT and/or PE who are intolerant to warfarin or not responding to warfarin.

During the study there will be 3 visits at day zero, week 6, and at day 90. Patients will be monitored closely for any bleeding complications.

During these visits, blood will be drawn for platelet counts, renal function, hematocrit, and transaminase level.

Primary endpoints

  1. Recurrent acute symptomatic DVT confirmed by venous ultrasound and/or CT scan
  2. Recurrent acute symptomatic PE confirmed by chest CT scan
  3. Major hemorrhage defined as spinal, retroperitoneal or intracranial bleeding, drop in hemoglobin ≥2g/dl or transfusion ≥2U or surgical or medical intervention, death related to bleeding

Secondary endpoints

Comparison of Day Zero, 6 week, and Day 90 platelet counts, renal function, hematocrit and transaminase level

Drug Dose:

Patients enrolled in the study will receive a weight-based dose of fondaparinux as monotherapy for 90 days for the treatment of DVT and/or PE.

Weight < 50 kg - 5 mg daily Weight 50 - 100 kg - 7.5 mg daily Weight > 100 kg - 10 mg daily

Biostatistical Analysis:

Descriptive statistics will be performed using age, gender, and indication for long-term anticoagulation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Recurrent venous thromboembolism despite anticoagulation with warfarin(Or)
  2. Clinically important bleeding complications due to warfarin(Or)
  3. Inability to achieve the target INR on warfarin(Or)
  4. Nonbleeding side effects of warfarin, such as hair loss, rash, purple toe syndrome(Or)
  5. Patient with cancer on monotherapy with parenteral anticoagulation for DVT and/ or PE

    and

  6. Require at least 90 days of anticoagulation
  7. Require anticoagulation for objectively confirmed DVT and/or PE
  8. Age greater than 18 years
  9. Written informed consent

Exclusion Criteria:

  1. Patients with renal insufficiency, defined as creatinine > 1.5 mg/dl
  2. Patients in whom anticoagulation with any agent is deemed unsafe due to bleeding risk.
  3. Pregnancy
  4. Known hypersensitivity to fondaparinux
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00413504

Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
GlaxoSmithKline
Investigators
Principal Investigator: Samuel Z. Goldhaber, MD Brigham and Women's Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Brigham and Women's Hospital, Venous Thromboembolism Research Group
ClinicalTrials.gov Identifier: NCT00413504     History of Changes
Other Study ID Numbers: 2006-P-000599
Study First Received: December 7, 2006
Last Updated: February 2, 2009
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Brigham and Women's Hospital:
Fondaparinux
Monotherapy
Deep Vein thrombosis
Pulmonary Embolism
Anticoagulation

Additional relevant MeSH terms:
Embolism
Pulmonary Embolism
Thrombosis
Venous Thrombosis
Cardiovascular Diseases
Embolism and Thrombosis
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Fondaparinux
PENTA
Anticoagulants
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014