- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00000614
Prevention of Recurrent Venous Thromboembolism (PREVENT)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
BACKGROUND:
Venous thromboembolism is associated with more than 300,000 hospitalizations and results in thousands of deaths annually. Conventional therapy consists of intravenous heparin followed by oral anticoagulants usually given for three to six months. The recommended intensity of oral anticoagulants (warfarin) has been derived from clinical trials. Such therapy is usually quite effective. However, some patients develop recurrent disease after the oral anticoagulants are stopped. A recent randomized study evaluated the optimal duration of oral anticoagulant therapy. After acute treatment with heparin, subjects were treated with oral anticoagulants for either six weeks or six months with a target INR * of 2 to 2.85. There was no difference in mortality in the two groups. Recurrence was not seen while the patients were under treatment. When anticoagulants were stopped, recurrent thrombosis was documented in 18 percent of the patients treated for six weeks and in 9.5 percent of those treated for six months. The period of greatest risk of recurrence for the six weeks patients was immediately after therapy was stopped. There was a linear increase in cumulative risk of 5 to 6 percent per year for both treatment groups during the following 18 months.
For patients who have experienced idiopathic venous thrombosis, the risk of recurrence may continue even after several months of conventional therapy. Further prophylactic therapy might be beneficial for the patients who are at risk for late recurrence. But, because of the presumed risk of bleeding and inconvenience of monitoring standard warfarin therapy, most physicians usually limit treatment to three to six months.
In 1997, Simioni showed a cumulative recurrence rate of VTE of 39.7 percent among those with factor V Leiden mutation, with all recurrences occurring within three years, a rate 2.4 times higher than among individuals without the mutation. The factor V Leiden mutation is found in 4 to 6 percent of Caucasians and is the single most important cause of thromboembolism in a variety of conditions. Heterozygous carriers with the mutation have VTE at a younger age than do noncarriers. Among those with first VTE, the prevalence of the mutation is 15 to 40 percent and among those with a family history of VTE, as high as 50 percent. However, in a large study of men participating in the Physicians Health Study, those individuals with the mutation had an increased rate of VTE over time. These age-specific incidence rate differences ranged from 1.23 to 5.97 in those aged 70 or older. These data suggest that confounders other than genetic predisposition are important in the development of VTE.
* The INR or international normalized ratio is the ratio of patient prothrombin to control prothrombin multiplied by the international sensitivity index. The INR was introduced by the World Health Organization to standardize control of anticoagulant therapy internationally.
DESIGN NARRATIVE:
Multicenter, randomized, double-blind, placebo-controlled. A total of 253 patients were randomized to usual care plus placebo and a total of 255 patients to usual care plus a three-to-four year regimen of low-dose warfarin (target INR 1.5 to 2.0), which after initial titration required infrequent outpatient monitoring. Double-blind INR assessment and dose adjustment were performed every three months to ensure patient safety and to monitor compliance. Primary endpoints included recurrent venous thromboembolism, major bleeding episodes, and all-cause mortality. Separate analysis was performed of all-cause mortality in the total patient population and in those with factor V Leiden.
The study consisted of 52 clinical centers, a laboratory coordinating center, the clinical coordinating center, and the data coordinating center.
The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.
Study Type
Phase
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Masking: Double
Collaborators and Investigators
Investigators
- Robert Glynn, Brigham and Women's Hospital
Publications and helpful links
General Publications
- Ridker PM. Long-term, low-dose warfarin among venous thrombosis patients with and without factor V Leiden mutation: rationale and design for the Prevention of Recurrent Venous Thromboembolism (PREVENT) trial. Vasc Med. 1998;3(1):67-73. doi: 10.1177/1358836X9800300114.
- Ridker PM, Goldhaber SZ, Danielson E, Rosenberg Y, Eby CS, Deitcher SR, Cushman M, Moll S, Kessler CM, Elliott CG, Paulson R, Wong T, Bauer KA, Schwartz BA, Miletich JP, Bounameaux H, Glynn RJ; PREVENT Investigators. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med. 2003 Apr 10;348(15):1425-34. doi: 10.1056/NEJMoa035029. Epub 2003 Feb 24.
- Schafer AI. Warfarin for venous thromboembolism - walking the dosing tightrope. N Engl J Med. 2003 Apr 10;348(15):1478-80. doi: 10.1056/NEJMe030018. Epub 2003 Feb 24. No abstract available.
- Miles JS, Miletich JP, Goldhaber SZ, Hennekens CH, Ridker PM. G20210A mutation in the prothrombin gene and the risk of recurrent venous thromboembolism. J Am Coll Cardiol. 2001 Jan;37(1):215-8. doi: 10.1016/s0735-1097(00)01080-9.
- Sick PB, Brosteanu O, Ulrich M, Thiele H, Niebauer J, Busch I, Schuler G. Prospective randomized comparison of early and late results of a carbonized stent versus a high-grade stainless steel stent of identical design: the PREVENT Trial [corrected]. Am Heart J. 2005 Apr;149(4):681-8. doi: 10.1016/j.ahj.2004.07.011. Erratum In: Am Heart J. 2005 Jun;149(6):1136.
Study record dates
Study Major Dates
Study Start
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 117
- R01HL057951 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Heart Diseases
-
Baker Heart and Diabetes InstitutePrincess Alexandra Hospital, Brisbane, Australia; Royal Perth Hospital; Alice... and other collaboratorsRecruitingHeart Failure | Valve Heart DiseaseAustralia
-
Medical University of ViennaUnknownHeart Diseases | Heart Failure | Valvular Heart DiseaseAustria
-
Centre Chirurgical Marie LannelongueActive, not recruitingValvular Heart Disease | Valve Disease, Heart
-
Abiomed Inc.RecruitingHeart Diseases | Acute Decompensated Heart Failure | Congestive Heart Failure | Acute Heart FailureUnited States
-
Wuerzburg University HospitalRecruitingHeart Failure | Chronic Heart Failure | Chronic Heart DiseaseGermany
-
Aristotle University Of ThessalonikiRecruitingCardiovascular Diseases | Heart Failure | Valvular Heart Disease | Biochemical DysfunctionGreece
-
Kathirvel SubramaniamUniversity of Maryland, Baltimore; CSL BehringRecruitingHeart Failure,Congestive | Heart Disease End StageUnited States
-
University of MichiganTerminatedDiastolic Heart Failure | Hypertensive Heart DiseaseUnited States
-
Wake Forest UniversityNational Institute on Aging (NIA)CompletedHeart Failure, Congestive | Diastolic Heart FailureUnited States
-
University College, LondonBritish Heart Foundation; Horizon 2020 - European CommissionRecruitingValvular Heart DiseaseUnited Kingdom
Clinical Trials on warfarin
-
University Hospital, BrestCompleted
-
University Hospital, BrestCompletedRecurrent Venous Thromboembolism | Idiopathic Deep Vein ThrombosisFrance
-
University of PadovaCompleted
-
Federal University of São PauloFundação de Amparo à Pesquisa do Estado de São PauloCompletedAtrial FibrillationBrazil
-
Duke UniversityNational Heart, Lung, and Blood Institute (NHLBI); Duke Clinical Research InstituteTerminatedIdiopathic Pulmonary FibrosisUnited States
-
Azienda Ospedaliera Universitaria PoliclinicoCompletedDeep Vein ThrombosisItaly
-
National University Hospital, SingaporeUnknownIndications for Warfarin TherapySingapore, Malaysia
-
University of KarachiAdvanced Education & Research Center; Karachi Institute of Heart DiseasesRecruitingLeft Atrial Appendage Aneurysm | Mitral StenosisPakistan
-
Jonsson Comprehensive Cancer CenterNovartis PharmaceuticalsCompletedUnspecified Adult Solid Tumor, Protocol SpecificUnited States
-
Massachusetts General HospitalNational Heart, Lung, and Blood Institute (NHLBI)CompletedHeart Diseases | Cardiovascular Diseases | Cerebrovascular Disorders | Atrial Fibrillation | Arrhythmia | Cerebrovascular Accident | Thrombophlebitis | Cerebral Embolism and Thrombosis