scholarly journals Efficacy and safety of new oral anticoagulants in prophylaxis and treatment of venous thromboembolism

2010 ◽  
Vol 1 (1) ◽  
pp. 7
Author(s):  
Luca Masotti
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Oral Anticoagulants ◽  
Clinical Development ◽  
Ease Of Use ◽  
New Oral Anticoagulants ◽  
Phase Iii ◽  
Thrombin Inhibitors ◽  
Phase Iii Clinical Trials ◽  
Phase Iii Trials

One of the main innovation emerged in recent years in the field of venous thromboembolism (VTE) has been represented by the clinical development and marketing of new oral anticoagulant agents used for prophylaxis and acute treatment. These drugs are represented by direct thrombin inhibitors (anti-factor IIa) and the direct inhibitors of activated factor X (anti-Xa). The main achievementof these new agents is represented by their ease of use without laboratory monitoring or dose adjustment. Dabigatran (anti-factor IIa), rivaroxaban, and apixaban (anti-Xa) are in advanced phase of clinical development with concluded phase III trials. Up to now the results of efficacy and safetyof phase III clinical trials are available, while phase IV studies are currently ongoing. Overall, the phase III clinical trials showed the non inferiority of new oral anticoagulants in VTE prophylaxis of patients undergone to major orthopedic surgery, such as hip and knee arthroplasty, compared toconventional prophylaxis represented by subcutaneous low molecular weight heparin with similar safety. Moreover dabigatran has shown to be not inferior when compared to warfarin for the prevention of six months VTE recurrences, with a significative lower incidence of bleedings. Awaitingthe results of many other ongoing phase III trials, since now it is possible to think that, in the next future, new oral anticoagulants will be widely diffused in clinical practice for their ease of use and feasibility. In this review the Authors analyse the available results of phase III clinical trials for dabigatran, rivaroxaban and apixaban, focusing on the antithrombotic endpoints for prevention andtreatment of VTE and the bleeding risk. Moreover synthesis of ongoing trials will be displayed.

scholarly journals Efficacy and safety of new oral anticoagulants in prophylaxis and treatment of venous thromboembolism

2010 ◽  
Vol 1 (1) ◽  
pp. 7-26 ◽  
Author(s):  
Luca Masotti ◽  
Cecilia Becattini ◽  
Roberto Cappelli ◽  
Giancarlo Landini ◽  
Alessandro Pampana ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Oral Anticoagulants ◽  
Clinical Development ◽  
Ease Of Use ◽  
New Oral Anticoagulants ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Phase Iii Clinical Trials ◽  
Phase Iii Trials

One of the main innovation emerged in recent years in the field of venous thromboembolism (VTE) has been represented by the clinical development and marketing of new oral anticoagulant agents used for prophylaxis and acute treatment. These drugs are represented by direct thrombin inhibitors (anti-factor IIa) and the direct inhibitors of activated factor X (anti-Xa). The main achievement of these new agents is represented by their ease of use without laboratory monitoring or dose adjustment. Dabigatran (anti-factor IIa), rivaroxaban, and apixaban (anti-Xa) are in advanced phase of clinical development with concluded phase III trials. Up to now the results of efficacy and safety of phase III clinical trials are available, while phase IV studies are currently ongoing. Overall, the phase III clinical trials showed the non inferiority of new oral anticoagulants in VTE prophylaxis of patients undergone to major orthopedic surgery, such as hip and knee arthroplasty, compared to conventional prophylaxis represented by subcutaneous low molecular weight heparin with similar safety. Moreover dabigatran has shown to be not inferior when compared to warfarin for the prevention of six months VTE recurrences, with a significative lower incidence of bleedings. Awaiting the results of many other ongoing phase III trials, since now it is possible to think that, in the next future, new oral anticoagulants will be widely diffused in clinical practice for their ease of use and feasibility. In this review the Authors analyse the available results of phase III clinical trials for dabigatran, rivaroxaban and apixaban, focusing on the antithrombotic endpoints for prevention and treatment of VTE and the bleeding risk. Moreover synthesis of ongoing trials will be displayed.

Treatment and secondary prevention of venous thromboembolism in cancer patients

2012 ◽  
Vol 03 (03) ◽  
pp. 121-125
Author(s):  
I. Pabinger ◽  
C. Ay
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Phase Iii ◽  
Patients With Cancer ◽  
Potential Use

SummaryCancer is a major and independent risk factor of venous thromboembolism (VTE). In clinical practice, a high number of VTE events occurs in patients with cancer, and treatment of cancerassociated VTE differs in several aspects from treatment of VTE in the general population. However, treatment in cancer patients remains a major challenge, as the risk of recurrence of VTE as well as the risk of major bleeding during anticoagulation is substantially higher in patients with cancer than in those without cancer. In several clinical trials, different anticoagulants and regimens have been investigated for treatment of acute VTE and secondary prophylaxis in cancer patients to prevent recurrence. Based on the results of these trials, anticoagulant therapy with low-molecular-weight heparins (LMWH) has become the treatment of choice in cancer patients with acute VTE in the initial period and for extended and long-term anticoagulation for 3-6 months. New oral anticoagulants directly inhibiting thrombin or factor Xa, have been developed in the past decade and studied in large phase III clinical trials. Results from currently completed trials are promising and indicate their potential use for treatment of VTE. However, the role of the new oral thrombin and factor Xa inhibitors for VTE treatment in cancer patients still has to be clarified in further studies specifically focusing on cancer-associated VTE. This brief review will summarize the current strategies of initial and long-term VTE treatment in patients with cancer and discuss the potential use of the new oral anticoagulants.

Abstract 301: Evaluation Of Net Clinical Benefits Of New Oral Anticoagulants Used For Acute Venous Thromboembolism Treatment vs. Standard Therapy

2014 ◽  
Vol 7 (suppl_1) ◽  
Author(s):  
Alpesh Amin ◽  
Yonghua Jing ◽  
Jeffrey Trocio ◽  
Jay Lin ◽  
Melissa Lingohr-Smith ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Standard Therapy ◽  
Oral Anticoagulants ◽  
New Oral Anticoagulants ◽  
Phase Iii ◽  
Primary Efficacy ◽  
Clinical Benefits ◽  
Recurrent Vte ◽  
Event Rates

Background: Venous thromboembolism (VTE) is a significant healthcare burden, but is a preventable and treatable condition. The new oral anticoagulants (NOACs), apixaban, rivaroxaban, dabigatran, and edoxaban have all been shown in phase III trials to be noninferior in efficacy to standard therapies for acute VTE treatment, although there may be some differences in the bleeding rates among the NOACs. This study evaluated the net clinical benefits (NCB) of NOACs vs. standard therapies based on the AMPLIFY, EINSTEIN-Pooled analysis, RECOVER-1, RE-COVER II, and Hokusai-VTE trial results. Methods: Event rates of the primary efficacy and safety outcomes, as defined in each original trial, among VTE patients during trial periods were obtained from the published clinical trial data. Data from RECOVER-I and -II trials were combined to represent the findings for dabigatran since the two trials were of similar design. EINSTEIN-pooled (DVT and PE combined) data were used to represent findings for rivaroxaban. The combinations of rates for the primary efficacy endpoint, representing recurrent VTE or death and major bleedings (MB) were evaluated and defined as the NCB of each NOAC. Additionally, the number of VTE patients needed to treat (NNT) to avoid one event (e.g. VTE or MB) with each NOAC was also determined. Results: For patients treated in the VTE clinical trials, the differences in event rates of recurrent VTE or death for apixaban, rivaroxaban, dabigatran, and edoxaban vs. standard therapy were -0.43%, -0.23%, 0.20%, and -0.34%, respectively. The differences in event rates of MB for apixaban, rivaroxaban, dabigatran, and edoxaban vs. standard therapy were -1.26%, -0.78%, -0.43%, and -0.24%, respectively. The NCB improved for all NOAC treated patients, with those treated with apixaban (-1.69%) vs. standard therapy having the greatest NCB, followed by those treated with rivaroxaban (-1.01%), edoxaban (-0.58%), and dabigatran ( -0.23%) (Table 1). Conclusions: All NOACs were shown to be non-inferior to standard VTE treatments in clinical trials; however, apixaban may provide the optimal NCB with the lowest NNT. How these results translate into real-world outcomes or medical cost reductions will require further evaluation.

scholarly journals A Review of Phase III Clinical Trials of Prostate Cancer Chemoprevention

2007 ◽  
Vol 89 (3) ◽  
pp. 207-211 ◽  
Author(s):  
JF Thorpe ◽  
S Jain ◽  
TH Marczylo ◽  
AJ Gescher ◽  
WP Steward ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Cancer Prevention ◽  
Age Of Onset ◽  
Cancer Chemoprevention ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Prostate Cancer Prevention ◽  
Phase Iii Trials

INTRODUCTION Prostate cancer is an excellent target for chemoprevention strategies; given its late age of onset, any delay in carcinogenesis would lead to a reduction in its incidence. This article reviews all the completed and on-going phase III trials in prostate cancer chemoprevention. PATIENTS AND METHODS All phase III trials of prostate cancer chemoprevention were identified within a Medline search using the keywords ‘clinical trial, prostate cancer, chemoprevention’. RESULTS In 2003, the Prostate Cancer Prevention Trial (PCPT) became the first phase III clinical trial of prostate cancer prevention. This landmark study was terminated early due to the 24.8% reduction of prostate cancer prevalence over a 7-year period in those men taking the 5α-reductase inhibitor, finasteride. This article reviews the PCPT and the interpretation of the excess high-grade prostate cancer (HGPC) cases in the finasteride group. The lack of relationship between cumulative dose and the HGPC cases, and the possible sampling error of biopsies due to gland volume reduction in the finasteride group refutes the suggestion that this is a genuine increase in HGPC cases. The other on-going phase III clinical trials of prostate cancer chemoprevention – the REDUCE study using dutasteride, and the SELECT study using vitamin E and selenium – are also reviewed. CONCLUSIONS At present, finasteride remains the only intervention shown in long-term prospective phase III clinical trials to reduce the incidence of prostate cancer. Until we have the results of trials using alternative agents including the on-going REDUCE and SELECT trials, the advice given to men interested in prostate cancer prevention must include discussion of the results of the PCPT. The increased rate of HGPC in the finasteride group continues to generate debate; however, finasteride may still be suitable for prostate cancer prevention, particularly in men with lower urinary tract symptoms.

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