Clinical trial NCT00119457: Factor IX Inhibition in Thrombosis Prevention (The FIXIT Trial)
Official title: A Multi-Center, Placebo-Controlled Evaluation of the Safety and Efficacy of Three Weeks Extended VTE Prophylaxis With Daily Oral Doses of TTP889 After One Week of Standard Prophylactic Treatment Following Hip Fracture Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Venous Thromboembolism
Embolism and Thrombosis
Hip Fractures
Keywords: antithrombotic agents
anticoagulants
prophylaxis
embolism
deep vein thrombosis
hip fracture
Lead sponsor: vTv Therapeutics
Sponsor class: INDUSTRY
First posted: 2005-07-13
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine whether TTP889 prevents venous thromboembolism following surgery to repair hip fracture.

Detailed description: FIXIT is the first Phase 2 study of TTP889. The trial is a proof-of-concept study to determine the safety and antithrombotic efficacy of TTP889 in patients at risk for venous thromboembolism (VTE). The study is a multi-center, randomized, double-blind, parallel-group evaluation of 300 mg TTP889 or placebo, administered orally once daily for three weeks, in patients who have undergone surgery to repair unilateral fracture of the upper third of either femur and who have completed 5 to 9 days of postoperative prophylactic treatment for VTE.

Eligibility criteria: Inclusion Criteria:

* Must have undergone reparative surgery within 72 hours after unilateral hip fracture, defined as fracture of the upper third of either femur
* Must have started standard prophylactic treatment for VTE with low molecular weight heparin (LMWH) or heparin before surgery or within 24 hours after hip fracture surgery, and continued treatment with LMWH or heparin for at least five days, but not more than nine days, after surgery
* Last dose of LMWH or heparin must have been administered at least 12 hours, but not more than 48 hours, before dosing with study drug
* Females must have a negative serum pregnancy test
* Must weigh at least 45 kg
* Must demonstrate the mental and physical ability and willingness to follow all study-specific instructions
* Must be able to read, comprehend and sign the Ethics Committee-approved informed consent form

Exclusion Criteria:

* Evidence of active bleeding
* Clinical signs of VTE
* Any medical requirement for (or intention to use) continued anticoagulation after randomization through the end of study
* History of intracranial bleeding, hemorrhagic stroke, or gastrointestinal bleeding within 3 months of study start
* Presence of active malignant disease
* Hip fracture associated with multiple trauma, that places patient at excessive risk for hemorrhage or organ system failure, or that may make it difficult or impossible to perform bilateral lower limb venography
* Intention to take aspirin at doses greater than 325 mg/day
* Hemoglobin \< 5.45 mmol/L (9 g/dL), hematocrit \< 29%, or a platelet count \< 100,000/mL at the screening visit
* Elevated ALT or AST level \> 3.0 times the ULN, or an elevated total bilirubin \> 1.5 the ULN at the screening visit
* Creatinine \> 180 mmol/L (2.0 mg/dL) at the screening visit
* Any other laboratory value at screening that the Investigator considers to be clinically significant and warrants exclusion from the study
* Patient is currently breast feeding a child and wishes to continue breast feeding
* Previous allergy to contrast material or any other contraindications to perform bilateral lower limb venography
* The use of another investigational drug within 28 days of study entry

Primary outcomes:
measure: To evaluate the antithrombotic efficacy of TTP889, administered once daily for three weeks, in patients who have completed standard prophylactic treatment for deep vein thrombosis after hip fracture surgery.
measure: Evaluation of safety of once daily oral administration of TTP889 for three weeks
Secondary outcomes:
measure: To assess the correlation between peak and trough plasma concentrations of TTP889 and clinical safety and efficacy outcomes.
Other outcomes:
Locations:
city: Ceske Budejovice
country: Czech Republic
facility: Nemocnice Ceske Budejovice, Urazove oddeleni
city: Ostrava-Poruba
country: Czech Republic
facility: FN s Poliklinikou Ostrava, Traumatologicke Centrum
city: Praha 5
country: Czech Republic
facility: FN Motol, Ortopedicka Klinicka UK 2.LF a FN Notol
city: Praha 8
country: Czech Republic
facility: FN Na Bulovce, Ortopedicka Klinika IPVZ a 1.LF UK ORT, Budinova 2
city: Praha-2
country: Czech Republic
facility: VFN, I. Chirurgicka klinika
city: Aalborg
country: Denmark
facility: AAlborg Hospital
city: Farso
country: Denmark
facility: Ortopaedkirurgisk Klinik, Farso
city: Hellerup
country: Denmark
facility: Amtsygehuset i Gentofte
city: Herlev
country: Denmark
facility: KAS Herlev
city: Horsholm
country: Denmark
facility: Horsholm Hospital
city: Kobenhavn
country: Denmark
facility: H:S Bispebjerg Hospital
city: Silkeborg
country: Denmark
facility: Silkeborg Hospital
city: Alesund
country: Norway
facility: Orthopedics, Alesund Sykehus
city: Gjovik
country: Norway
facility: Skyehuset Innlandet HF
city: Lillehammer
country: Norway
facility: Skyehuset Innlandet HF
city: Tonsberg
country: Norway
facility: Halfdan Wilhelmsens Alle 17
city: Goteborg
country: Sweden
facility: Ortoped Kliniken, Sahlgrenska Universitetssjukhus, Ostra
city: Kungalv
country: Sweden
facility: Ortopedsektionen, Kirurgkliniken, Kungalvs Sjukhus
city: Molndal
country: Sweden
facility: Ortoped kliniken, Sahlgrenska Universitetssjukhus
city: Udevalla
country: Sweden
facility: Ortoped kliniken, NU-sjukvarden, Udevalla Sjukhus
city: Varberg
country: Sweden
facility: Ortoped kliniken, Sjukhuset i Varberg
Study officials:
affiliation: Dept of Orthopaedics, Goteborg University
name: Bengt I Eriksson, MD
role: STUDY_CHAIR
affiliation: vTv Therapeutics
name: David P Ward, MD
role: STUDY_DIRECTOR
References:
citation: Eriksson BI, Dahl OE, Lassen MR, Ward DP, Rothlein R, Davis G, Turpie AG; Fixit Study Group. Partial factor IXa inhibition with TTP889 for prevention of venous thromboembolism: an exploratory study. J Thromb Haemost. 2008 Mar;6(3):457-63. doi: 10.1111/j.1538-7836.2007.02872.x. Epub 2007 Dec 12.