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Fondaparinux as Monotherapy for DVT and/or Pulmonary Embolism
Fondaparinux as Monotherapy for Deep Vein Thrombosis and/or Pulmonary Embolism (Pilot Study)
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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:
- Recurrent venous thromboembolism despite anticoagulation with warfarin
- Clinically important bleeding complications due to warfarin
- Inability to achieve target International Normalized Ratio (INR) on warfarin
- 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
- Recurrent acute symptomatic DVT confirmed by venous ultrasound and/or CT scan
- Recurrent acute symptomatic PE confirmed by chest CT scan
- 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.
Studietype
Inschrijving (Werkelijk)
Fase
- Niet toepasbaar
Contacten en locaties
Studie Locaties
-
-
Massachusetts
-
Boston, Massachusetts, Verenigde Staten, 02115
- Brigham and Women's Hospital
-
-
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- Recurrent venous thromboembolism despite anticoagulation with warfarin(Or)
- Clinically important bleeding complications due to warfarin(Or)
- Inability to achieve the target INR on warfarin(Or)
- Nonbleeding side effects of warfarin, such as hair loss, rash, purple toe syndrome(Or)
Patient with cancer on monotherapy with parenteral anticoagulation for DVT and/ or PE
and
- Require at least 90 days of anticoagulation
- Require anticoagulation for objectively confirmed DVT and/or PE
- Age greater than 18 years
- Written informed consent
Exclusion Criteria:
- Patients with renal insufficiency, defined as creatinine > 1.5 mg/dl
- Patients in whom anticoagulation with any agent is deemed unsafe due to bleeding risk.
- Pregnancy
- Known hypersensitivity to fondaparinux
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
---|---|
Recurrent acute symptomatic DVT confirmed by venous ultrasound and/or CT scan
Tijdsspanne: 90 Days
|
90 Days
|
Recurrent acute symptomatic PE confirmed by chest CT scan
Tijdsspanne: 90 Days
|
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
Tijdsspanne: 90 Days
|
90 Days
|
Secundaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
---|---|
Comparison of Day Zero, 6 week, and Day 90 platelet counts, renal function, hematocrit and transaminase level
Tijdsspanne: 90 Days
|
90 Days
|
Medewerkers en onderzoekers
Sponsor
Medewerkers
Onderzoekers
- Hoofdonderzoeker: Samuel Z. Goldhaber, MD, Brigham and Women's Hospital
Publicaties en nuttige links
Algemene publicaties
- Buller HR, Davidson BL, Decousus H, Gallus A, Gent M, Piovella F, Prins MH, Raskob G, van den Berg-Segers AE, Cariou R, Leeuwenkamp O, Lensing AW; Matisse Investigators. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med. 2003 Oct 30;349(18):1695-702. doi: 10.1056/NEJMoa035451. Erratum In: N Engl J Med. 2004 Jan 22;350(4):423.
- Petitou M, Duchaussoy P, Herbert JM, Duc G, El Hajji M, Branellec JF, Donat F, Necciari J, Cariou R, Bouthier J, Garrigou E. The synthetic pentasaccharide fondaparinux: first in the class of antithrombotic agents that selectively inhibit coagulation factor Xa. Semin Thromb Hemost. 2002 Aug;28(4):393-402. doi: 10.1055/s-2002-34309.
- Buller HR, Davidson BL, Decousus H, Gallus A, Gent M, Piovella F, Prins MH, Raskob G, Segers AE, Cariou R, Leeuwenkamp O, Lensing AW; Matisse Investigators. Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial. Ann Intern Med. 2004 Jun 1;140(11):867-73. doi: 10.7326/0003-4819-140-11-200406010-00007.
Nuttige links
Studie record data
Bestudeer belangrijke data
Studie start
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Hart-en vaatziekten
- Vaatziekten
- Ziekten van de luchtwegen
- Longziekten
- Embolie en trombose
- Embolie
- Trombose
- Veneuze trombose
- Longembolie
- Moleculaire mechanismen van farmacologische werking
- Enzymremmers
- Fibrinolytische middelen
- Fibrine modulerende middelen
- Proteaseremmers
- Factor Xa-remmers
- Antithrombinen
- Serineproteïnaseremmers
- Anticoagulantia
- Fondaparinux
- PENTA
Andere studie-ID-nummers
- 2006-P-000599
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .
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