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History of Changes for Study: NCT02295475
Apixaban for the Secondary Prevention of Thromboembolism Among Patients With the AntiphosPholipid Syndrome (ASTRO-APS)
Latest version (submitted June 13, 2019) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 November 19, 2014 None (earliest Version on record)
2 March 4, 2015 Recruitment Status, Study Status, Contacts/Locations and Oversight
3 August 25, 2015 Study Status and Study Description
4 October 29, 2015 Contacts/Locations, Study Status, Eligibility, Arms and Interventions, Study Description and Oversight
5 August 26, 2016 Study Status, IPDSharing and Eligibility
6 December 29, 2016 Study Status and Study Description
7 January 3, 2017 Study Status and Study Design
8 June 21, 2017 Study Status
9 September 10, 2018 Oversight and Study Status
10 February 25, 2019 Contacts/Locations and Study Status
11 June 13, 2019 Recruitment Status, Study Status, Sponsor/Collaborators, Contacts/Locations, Outcome Measures, Arms and Interventions, Study Description, Study Identification, Eligibility and Conditions
Comparison Format:

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Changes (Side-by-Side) for Study: NCT02295475
November 19, 2014 (v1) -- June 21, 2017 (v8)

Changes in: Study Status, Contacts/Locations, Study Description, Oversight, IPDSharing, Eligibility, Arms and Interventions and Study Design

Study Identification
Unique Protocol ID: CV185-357 CV185-357
Brief Title: Apixaban for the Secondary Prevention of Thromboembolism Among Patients With the AntiphosPholipid Syndrome (ASTRO-APS)Apixaban for the Secondary Prevention of Thromboembolism Among Patients With the AntiphosPholipid Syndrome (ASTRO-APS)
Official Title: Apixaban for the Secondary Prevention of Thromboembolism: a Prospective Randomized Outcome Pilot Study Among Patients With the AntiphosPholipid Syndrome Apixaban for the Secondary Prevention of Thromboembolism: a Prospective Randomized Outcome Pilot Study Among Patients With the AntiphosPholipid Syndrome
Secondary IDs:
Study Status
Record Verification: November 2014 June 2017
Overall Status: Not yet recruiting Recruiting
Study Start: January 2015 February 2015
Primary Completion: December 2017 [Anticipated ] December 2019 [Anticipated ]
Study Completion: December 2017 [Anticipated ] December 2019 [Anticipated ]
First Submitted: November 18, 2014 November 18, 2014
First Submitted that
Met QC Criteria:
November 19, 2014 November 19, 2014
First Posted: November 20, 2014 [Estimate ] November 20, 2014 [Estimate ]
Last Update Submitted that
Met QC Criteria:
November 19, 2014 June 21, 2017
Last Update Posted: November 20, 2014 [Estimate ] June 23, 2017 [Actual ]
Sponsor/Collaborators
Sponsor: Intermountain Health Care, Inc. Intermountain Health Care, Inc.
Responsible Party: Sponsor Sponsor
Collaborators: Bristol-Myers Squibb Bristol-Myers Squibb
Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes Yes
Study Description
Brief Summary: ASTRO-APS is a prospective, randomized, open-label blinded endpoint pilot study among patients with a clinical diagnosis of the AntiPhospholipid Syndrome and are already taking an anticoagulant for the secondary prevention of thrombosis (blood clots). Subjects will be randomized to receive either warfarin (target INR range 2-3) or apixaban 2.5mg twice daily. Patients will follow up with the study team for 13 months. 2 in-clinic follow-up visits will be performed as well as 4 telephone follow-up visits. ASTRO-APS is a prospective, randomized, open-label blinded endpoint pilot study among patients with a clinical diagnosis of the AntiPhospholipid Syndrome and are already taking an anticoagulant for the secondary prevention of thrombosis (blood clots). Subjects will be randomized to receive either warfarin (target INR range 2-3) or apixaban 5 mg twice daily. Patients will follow up with the study team for 13 months. 2 in-clinic follow-up visits will be performed as well as 4 telephone follow-up visits. Study participants will be asked to consent to follow up telephone calls and questionnaires at 3 month intervals following the completion of the study procedures for the main portion of the study.
Detailed Description:

This pilot study has two primary aims. The first is to identify patients with a clinical diagnosis of APS and then describe their recruitment, enrollment, screening failure rate, adherence to therapy, clinical characteristics, and APS diagnostic criteria in terms of broadly accepted published standards. Essential in this aim is capture of ability to identify, recruit, randomize, and retain patients with APS receiving a direct oral anticoagulant. We will also report compliance and patient satisfaction; central to durable anticoagulation management.

The second aim is to report rates of thrombosis (arterial or venous) and death caused by thrombosis, as well as major bleeding plus clinically relevant non-major bleeding over one year among APS patients randomized to either warfarin or apixaban. As such, we will report the rate of Thrombosis (arterial and/or venous) [ Time Frame: Up to 13 months after enrollment ] [ Designated as safety issue: No ] and Major and non-major bleeding [ Time Frame: Up to 13 months after enrollment ] [ Designated as safety issue: Yes ]

Conditions
Conditions: Antiphospholipid Syndrome
Thrombosis
Antiphospholipid Syndrome
Thrombosis
Keywords:
Study Design
Study Type: InterventionalInterventional
Primary Purpose: PreventionPrevention
Study Phase: Phase 2/Phase 3Phase 4
Interventional Study Model: Parallel Assignment Parallel Assignment
Number of Arms: 22
Masking: None (Open Label)None (Open Label)
Allocation: RandomizedRandomized
Enrollment: 200 [Anticipated ] 200 [Anticipated ]
Arms and Interventions
Arms Assigned Interventions
Experimental: Apixaban
Subjects will receive apixaban 2.5 5 mg tablets taken twice daily for the duration of the study.
Drug: Apixaban
Study subjects will be randomized to receive Apixaban.
Active Comparator: Warfarin
Subjects will receive warfarin for the duration of the study. The dose and how frequently warfarin is taken depends on the results of the patient's INR blood test(s). The target INR range for this study is 2-3.
Drug: Warfarin
Study subjects will be randomized to receive Warfarin.
Outcome Measures
Primary Outcome Measures:
1. Rate of Thrombosis (arterial and/or venous)
Up to 13 months after enrollment
Rate of Thrombosis (arterial and/or venous)
Up to 13 months after enrollment
2. Major and non-major bleeding
Up to 13 months after enrollment
Major and non-major bleeding
Up to 13 months after enrollment
Eligibility
Minimum Age: 18 Years 18 Years
Maximum Age:
Sex: All All
Gender Based:
Accepts Healthy Volunteers: NoNo
Criteria:

Inclusion Criteria:

  1. Be ≥ 18 years of age
  2. Have a clinical diagnosis of the APS for which the patient is receiving anticoagulation therapy for the secondary prevention of thrombosis

2.a. Anticoagulation is defined as warfarin sodium titrated at the discretion of the clinician to a target INR 2.5 (range 2-3), 3.0 (range 2.5-3.5), or 3.5 (range 3-4).

2. b. Should the patient be receiving some other form of anticoagulation (apixaban, rivaroxaban, edoxaban, dabigatran etexilate, low-molecular weight heparin) and are willing to be randomized to warfarin with a target INR 2.5 or apixaban 2.5mg PO BID and they meet all other inclusion criteria

3. Have completed at least 6months of anticoagulation for the indication of thrombosis

4. Be willing to provide informed consent to contact the subjects anticoagulation provider for INRs and dosing as well as details regarding any adverse events

5. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.

6. Women must not be breastfeeding

7. WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug apixaban plus 5 half-lives of study drug apixaban (3 days) plus 30 days (duration of ovulatory cycle) for a total of 33 days post-treatment completion.

8. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug apixaban plus 5 half-lives of the study drug apixaban (3 days) plus 90 days (duration of sperm turnover) for a total of 93 days post-treatment completion.

9. Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However they must still undergo pregnancy testing.

Exclusion Criteria:

  1. Another indication for long-term anticoagulation for which no FDA approval of apixaban exists (e.g. mechanical heart valve)
  2. Another indication for long-term anticoagulation with apixaban that requires apixaban be taken at a dose that differs from the study dose
  3. A life expectancy of less than 1 year
  4. Is unable to attend follow-up appointments
  5. Is participating in a conflicting clinical trial or has participated in a trial within the last 30 days
  6. Is receiving concomitant dual antiplatelet therapy
  7. Requires aspirin dose of greater than 165mg daily
  8. A hemoglobin level of less than 8 mg per deciliter
  9. A platelet count of less than 50,000 per cubic millimeter
  10. Serum creatinine level of more than 2.5 mg per deciliter (221 μmol per liter) or a calculated creatinine clearance of less than 25 ml per minute
  11. Alanine aminotransferase or aspartate aminotransferase level greater than 2 times the upper limit of the normal range
  12. A total bilirubin more than 1.5 times the upper limit of the normal range.
  13. Have active cancer for which treatment (chemotherapy/radiation therapy) is being delivered or has been delivered within the last 3 months
  14. Are actively receiving a strong dual inhibitor of CYP3A4 and P-gp, such as:

14.a Ketoconazole 14.b Itraconazole 14.c Ritonavir 14.d clarithromycin

15. Are actively taking a strong dual inducer of CYP3A4 and P-gp, such as: 15.a rifampin 15.b carbamazepine 15.c phenytoin 15.d St. John's wort

16. Intend pregnancy or breastfeeding within the next year

17. Have a known allergy to apixaban, rivaroxaban, or edoxaban

18. Have experienced thrombosis while receiving warfarin at a target INR of 2-3 and have been assigned a higher target INR at the discretion of their clinician.

Inclusion Criteria:

  1. Be ≥ 18 years of age
  2. Have a clinical diagnosis of the APS for which the patient is receiving anticoagulation therapy for the secondary prevention of thrombosis

2.a. Anticoagulation is defined as warfarin sodium titrated at the discretion of the clinician to a target INR 2.5 (range 2-3), 3.0 (range 2.5-3.5), or 3.5 (range 3-4).

2. b. Should the patient be receiving some other form of anticoagulation (apixaban, rivaroxaban, edoxaban, dabigatran etexilate, low-molecular weight heparin) and are willing to be randomized to warfarin with a target INR 2.5 or apixaban 5 mg PO BID and they meet all other inclusion criteria

3. Have completed at least 6months of anticoagulation for the indication of thrombosis and are without acute neurologic symptoms consistent with thrombosis, CVA, or TIA for a minimum of six months.

4. Be willing to provide informed consent to contact the subjects anticoagulation provider for INRs and dosing as well as details regarding any adverse events

5. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.

6. Women must not be breastfeeding

7. Women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug apixaban plus 5 half-lives of study drug apixaban (3 days) plus 30 days (duration of ovulatory cycle) for a total of 33 days post-treatment completion.

8. Males who are sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug apixaban plus 5 half-lives of the study drug apixaban (3 days) plus 90 days (duration of sperm turnover) for a total of 93 days post-treatment completion.

9. Azoospermic males and women of childbearing potential who are continuously not heterosexually active are exempt from contraceptive requirements. However they must still undergo pregnancy testing.

10. Be willing to undergo magnetic resonance imaging (MRI) of the brain

Exclusion Criteria:

  1. Another indication for long-term anticoagulation for which no FDA approval of apixaban exists (e.g. mechanical heart valve)
  2. A life expectancy of less than 1 year
  3. Is unable to attend follow-up appointments
  4. Is participating in a conflicting clinical trial or has participated in a trial within the last 30 days
  5. Is receiving concomitant dual antiplatelet therapy
  6. Requires aspirin dose of greater than 165mg daily
  7. A hemoglobin level of less than 8 mg per deciliter
  8. A platelet count of less than 50,000 per cubic millimeter
  9. Serum creatinine level of more than 2.5 mg per deciliter (221 μmol per liter) or a calculated creatinine clearance of less than 25 ml per minute
  10. Alanine aminotransferase or aspartate aminotransferase level greater than 2 times the upper limit of the normal range
  11. A total bilirubin more than 1.5 times the upper limit of the normal range.
  12. Have active cancer for which treatment (chemotherapy/radiation therapy) is being delivered or has been delivered within the last 3 months
  13. Are actively receiving a strong dual inhibitor of CYP3A4 and P-gp, such as:

13.a Ketoconazole 13.b Itraconazole 13.c Ritonavir 13.d clarithromycin

14. Are actively taking a strong dual inducer of CYP3A4 and P-gp, such as: 14.a rifampin 14.b carbamazepine 14.c phenytoin 14.d St. John's wort

15. Intend pregnancy or breastfeeding within the next year

16. Have a known allergy to apixaban, rivaroxaban, or edoxaban

17. Have experienced thrombosis while receiving warfarin at a target INR of 2-3 and have been assigned a higher target INR at the discretion of their clinician.

18. Patients with active pathological bleeding.

19. A history of arterial thromboembolism (e.g., stroke, myocardial infarction or other arterial thrombosis)

20. Requires clopidogrel, tigacrolor, prasugrel, or another P2Y12 inhibitor

21. Have a history of catastrophic APS (CAPS) as defined by clinical routine

22. Have radiographic evidence of prior arterial thrombosis on MRI as defined per clinical routine upon screening MRI

23. At the discretion of the investigator are considered to not be candidates secondary to s a safety concern.

Contacts/Locations
Central Contact: Scott C Woller, MD
Telephone: 8015073376
Email: Scott.Woller@imail.org
Scott C Woller, MD
Telephone: 801-507-3376
Email: Scott.Woller@imail.org
Central Contact Backup: Eric Johnson, BS
Telephone: 8015074791
Email: Eric.Johnson@imail.org
Valerie Aston, BS
Telephone: 801-507-4606
Email: Valerie.Aston@imail.org
Study Officials: Scott C Woller, MD
Principal Investigator
Intermountain Health Care, Inc.
Scott C Woller, MD
Principal Investigator
Intermountain Health Care, Inc.
Locations: United States, Utah
Intermountain Medical Center
[Recruiting]
Murray, Utah, United States, 84157
Contact: Shauna Bruun 801-408-2137 Shauna.Bruun@imail.org
IPDSharing
Plan to Share IPD: No
References
Citations: Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 Feb;4(2):295-306. PubMed 16420554Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 Feb;4(2):295-306. PubMed 16420554
Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Porcari A, Raskob GE, Weitz JI; AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):699-708. doi: 10.1056/NEJMoa1207541. Epub 2012 Dec 8. PubMed 23216615Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Porcari A, Raskob GE, Weitz JI; AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):699-708. doi: 10.1056/NEJMoa1207541. Epub 2012 Dec 8. PubMed 23216615
Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29;369(9):799-808. doi: 10.1056/NEJMoa1302507. Epub 2013 Jul 1. PubMed 23808982Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29;369(9):799-808. doi: 10.1056/NEJMoa1302507. Epub 2013 Jul 1. PubMed 23808982
Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S, Flaker G, Avezum A, Hohnloser SH, Diaz R, Talajic M, Zhu J, Pais P, Budaj A, Parkhomenko A, Jansky P, Commerford P, Tan RS, Sim KH, Lewis BS, Van Mieghem W, Lip GY, Kim JH, Lanas-Zanetti F, Gonzalez-Hermosillo A, Dans AL, Munawar M, O'Donnell M, Lawrence J, Lewis G, Afzal R, Yusuf S; AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011 Mar 3;364(9):806-17. doi: 10.1056/NEJMoa1007432. Epub 2011 Feb 10. PubMed 21309657Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S, Flaker G, Avezum A, Hohnloser SH, Diaz R, Talajic M, Zhu J, Pais P, Budaj A, Parkhomenko A, Jansky P, Commerford P, Tan RS, Sim KH, Lewis BS, Van Mieghem W, Lip GY, Kim JH, Lanas-Zanetti F, Gonzalez-Hermosillo A, Dans AL, Munawar M, O'Donnell M, Lawrence J, Lewis G, Afzal R, Yusuf S; AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011 Mar 3;364(9):806-17. doi: 10.1056/NEJMoa1007432. Epub 2011 Feb 10. PubMed 21309657
Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981-92. doi: 10.1056/NEJMoa1107039. Epub 2011 Aug 27. PubMed 21870978Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981-92. doi: 10.1056/NEJMoa1107039. Epub 2011 Aug 27. PubMed 21870978
Cano SJ, Lamping DL, Bamber L, Smith S. The Anti-Clot Treatment Scale (ACTS) in clinical trials: cross-cultural validation in venous thromboembolism patients. Health Qual Life Outcomes. 2012 Sep 26;10:120. doi: 10.1186/1477-7525-10-120. PubMed 23013426Cano SJ, Lamping DL, Bamber L, Smith S. The Anti-Clot Treatment Scale (ACTS) in clinical trials: cross-cultural validation in venous thromboembolism patients. Health Qual Life Outcomes. 2012 Sep 26;10:120. doi: 10.1186/1477-7525-10-120. PubMed 23013426
Bamber L, Wang MY, Prins MH, Ciniglio C, Bauersachs R, Lensing AW, Cano SJ. Patient-reported treatment satisfaction with oral rivaroxaban versus standard therapy in the treatment of acute symptomatic deep-vein thrombosis. Thromb Haemost. 2013 Oct;110(4):732-41. doi: 10.1160/TH13-03-0243. Epub 2013 Jul 11. PubMed 23846019Bamber L, Wang MY, Prins MH, Ciniglio C, Bauersachs R, Lensing AW, Cano SJ. Patient-reported treatment satisfaction with oral rivaroxaban versus standard therapy in the treatment of acute symptomatic deep-vein thrombosis. Thromb Haemost. 2013 Oct;110(4):732-41. doi: 10.1160/TH13-03-0243. Epub 2013 Jul 11. PubMed 23846019
Cohen H, Machin SJ. Antithrombotic treatment failures in antiphospholipid syndrome: the new anticoagulants? Lupus. 2010 Apr;19(4):486-91. doi: 10.1177/0961203310361355. Review. PubMed 20353992Cohen H, Machin SJ. Antithrombotic treatment failures in antiphospholipid syndrome: the new anticoagulants? Lupus. 2010 Apr;19(4):486-91. doi: 10.1177/0961203310361355. Review. PubMed 20353992
Alarcón-Segovia D, Pérez-Vázquez ME, Villa AR, Drenkard C, Cabiedes J. Preliminary classification criteria for the antiphospholipid syndrome within systemic lupus erythematosus. Semin Arthritis Rheum. 1992 Apr;21(5):275-86. PubMed 1604324Alarcón-Segovia D, Pérez-Vázquez ME, Villa AR, Drenkard C, Cabiedes J. Preliminary classification criteria for the antiphospholipid syndrome within systemic lupus erythematosus. Semin Arthritis Rheum. 1992 Apr;21(5):275-86. PubMed 1604324
Asherson RA, Khamashta MA, Ordi-Ros J, Derksen RH, Machin SJ, Barquinero J, Outt HH, Harris EN, Vilardell-Torres M, Hughes GR. The "primary" antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore). 1989 Nov;68(6):366-74. PubMed 2509856Asherson RA, Khamashta MA, Ordi-Ros J, Derksen RH, Machin SJ, Barquinero J, Outt HH, Harris EN, Vilardell-Torres M, Hughes GR. The "primary" antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore). 1989 Nov;68(6):366-74. PubMed 2509856
Vianna JL, Khamashta MA, Ordi-Ros J, Font J, Cervera R, Lopez-Soto A, Tolosa C, Franz J, Selva A, Ingelmo M, et al. Comparison of the primary and secondary antiphospholipid syndrome: a European Multicenter Study of 114 patients. Am J Med. 1994 Jan;96(1):3-9. PubMed 8304360Vianna JL, Khamashta MA, Ordi-Ros J, Font J, Cervera R, Lopez-Soto A, Tolosa C, Franz J, Selva A, Ingelmo M, et al. Comparison of the primary and secondary antiphospholipid syndrome: a European Multicenter Study of 114 patients. Am J Med. 1994 Jan;96(1):3-9. PubMed 8304360
Cervera R, Serrano R, Pons-Estel GJ, Ceberio-Hualde L, Shoenfeld Y, de Ramón E, Buonaiuto V, Jacobsen S, Zeher MM, Tarr T, Tincani A, Taglietti M, Theodossiades G, Nomikou E, Galeazzi M, Bellisai F, Meroni PL, Derksen RH, de Groot PG, Baleva M, Mosca M, Bombardieri S, Houssiau F, Gris JC, Quéré I, Hachulla E, Vasconcelos C, Fernández-Nebro A, Haro M, Amoura Z, Miyara M, Tektonidou M, Espinosa G, Bertolaccini ML, Khamashta MA; Euro-Phospholipid Project Group (European Forum on Antiphospholipid Antibodies). Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis. 2015 Jun;74(6):1011-8. doi: 10.1136/annrheumdis-2013-204838. Epub 2014 Jan 24. PubMed 24464962Cervera R, Serrano R, Pons-Estel GJ, Ceberio-Hualde L, Shoenfeld Y, de Ramón E, Buonaiuto V, Jacobsen S, Zeher MM, Tarr T, Tincani A, Taglietti M, Theodossiades G, Nomikou E, Galeazzi M, Bellisai F, Meroni PL, Derksen RH, de Groot PG, Baleva M, Mosca M, Bombardieri S, Houssiau F, Gris JC, Quéré I, Hachulla E, Vasconcelos C, Fernández-Nebro A, Haro M, Amoura Z, Miyara M, Tektonidou M, Espinosa G, Bertolaccini ML, Khamashta MA; Euro-Phospholipid Project Group (European Forum on Antiphospholipid Antibodies). Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis. 2015 Jun;74(6):1011-8. doi: 10.1136/annrheumdis-2013-204838. Epub 2014 Jan 24. PubMed 24464962
Galli M, Luciani D, Bertolini G, Barbui T. Anti-beta 2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome. Blood. 2003 Oct 15;102(8):2717-23. Epub 2003 Jun 19. Review. PubMed 12816875Galli M, Luciani D, Bertolini G, Barbui T. Anti-beta 2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome. Blood. 2003 Oct 15;102(8):2717-23. Epub 2003 Jun 19. Review. PubMed 12816875
Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, Hailpern SM, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell C, Roger V, Sorlie P, Steinberger J, Thom T, Wilson M, Hong Y; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008 Jan 29;117(4):e25-146. Epub 2007 Dec 17. Erratum in: Circulation. 2010 Jul 6;122(1):e10. Kissela, Bret [corrected to Kissela, Brett]. PubMed 18086926Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, Hailpern SM, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell C, Roger V, Sorlie P, Steinberger J, Thom T, Wilson M, Hong Y; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008 Jan 29;117(4):e25-146. Epub 2007 Dec 17. Erratum in: Circulation. 2010 Jul 6;122(1):e10. Kissela, Bret [corrected to Kissela, Brett]. PubMed 18086926
Crowther MA, Ginsberg JS, Julian J, Denburg J, Hirsh J, Douketis J, Laskin C, Fortin P, Anderson D, Kearon C, Clarke A, Geerts W, Forgie M, Green D, Costantini L, Yacura W, Wilson S, Gent M, Kovacs MJ. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med. 2003 Sep 18;349(12):1133-8. Erratum in: N Engl J Med. 2003 Dec 25;349(26):2577. N Engl J Med. 2004 Jul 8;351(2):200. PubMed 13679527Crowther MA, Ginsberg JS, Julian J, Denburg J, Hirsh J, Douketis J, Laskin C, Fortin P, Anderson D, Kearon C, Clarke A, Geerts W, Forgie M, Green D, Costantini L, Yacura W, Wilson S, Gent M, Kovacs MJ. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med. 2003 Sep 18;349(12):1133-8. Erratum in: N Engl J Med. 2003 Dec 25;349(26):2577. N Engl J Med. 2004 Jul 8;351(2):200. PubMed 13679527
Petri M. Thrombosis and systemic lupus erythematosus: the Hopkins Lupus Cohort perspective. Scand J Rheumatol. 1996;25(4):191-3. Review. PubMed 8792794Petri M. Thrombosis and systemic lupus erythematosus: the Hopkins Lupus Cohort perspective. Scand J Rheumatol. 1996;25(4):191-3. Review. PubMed 8792794
Witt DM, Sadler MA, Shanahan RL, Mazzoli G, Tillman DJ. Effect of a centralized clinical pharmacy anticoagulation service on the outcomes of anticoagulation therapy. Chest. 2005 May;127(5):1515-22. PubMed 15888822Witt DM, Sadler MA, Shanahan RL, Mazzoli G, Tillman DJ. Effect of a centralized clinical pharmacy anticoagulation service on the outcomes of anticoagulation therapy. Chest. 2005 May;127(5):1515-22. PubMed 15888822
van Walraven C, Jennings A, Oake N, Fergusson D, Forster AJ. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest. 2006 May;129(5):1155-66. Review. PubMed 16685005van Walraven C, Jennings A, Oake N, Fergusson D, Forster AJ. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest. 2006 May;129(5):1155-66. Review. PubMed 16685005
Hansson L, Hedner T, Dahlöf B. Prospective randomized open blinded end-point (PROBE) study. A novel design for intervention trials. Prospective Randomized Open Blinded End-Point. Blood Press. 1992 Aug;1(2):113-9. PubMed 1366259Hansson L, Hedner T, Dahlöf B. Prospective randomized open blinded end-point (PROBE) study. A novel design for intervention trials. Prospective Randomized Open Blinded End-Point. Blood Press. 1992 Aug;1(2):113-9. PubMed 1366259
Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. doi: 10.1056/NEJMoa0905561. Epub 2009 Aug 30. Erratum in: N Engl J Med. 2010 Nov 4;363(19):1877. PubMed 19717844Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. doi: 10.1056/NEJMoa0905561. Epub 2009 Aug 30. Erratum in: N Engl J Med. 2010 Nov 4;363(19):1877. PubMed 19717844
Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos A, Tapson V. Extended-duration rivaroxaban thromboprophylaxis in acutely ill medical patients: MAGELLAN study protocol. J Thromb Thrombolysis. 2011 May;31(4):407-16. doi: 10.1007/s11239-011-0549-x. PubMed 21359646Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos A, Tapson V. Extended-duration rivaroxaban thromboprophylaxis in acutely ill medical patients: MAGELLAN study protocol. J Thromb Thrombolysis. 2011 May;31(4):407-16. doi: 10.1007/s11239-011-0549-x. PubMed 21359646
EINSTEIN-PE Investigators, Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287-97. doi: 10.1056/NEJMoa1113572. Epub 2012 Mar 26. PubMed 22449293EINSTEIN-PE Investigators, Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287-97. doi: 10.1056/NEJMoa1113572. Epub 2012 Mar 26. PubMed 22449293
Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F, Turpie AG; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2776-86. doi: 10.1056/NEJMoa076016. PubMed 18579812Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F, Turpie AG; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2776-86. doi: 10.1056/NEJMoa076016. PubMed 18579812
Rosove MH, Brewer PM. Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med. 1992 Aug 15;117(4):303-8. PubMed 1637025Rosove MH, Brewer PM. Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med. 1992 Aug 15;117(4):303-8. PubMed 1637025
Khamashta MA, Cuadrado MJ, Mujic F, Taub NA, Hunt BJ, Hughes GR. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med. 1995 Apr 13;332(15):993-7. PubMed 7885428Khamashta MA, Cuadrado MJ, Mujic F, Taub NA, Hunt BJ, Hughes GR. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med. 1995 Apr 13;332(15):993-7. PubMed 7885428
Ruiz-Irastorza G, Khamashta MA, Hunt BJ, Escudero A, Cuadrado MJ, Hughes GR. Bleeding and recurrent thrombosis in definite antiphospholipid syndrome: analysis of a series of 66 patients treated with oral anticoagulation to a target international normalized ratio of 3.5. Arch Intern Med. 2002 May 27;162(10):1164-9. PubMed 12020188Ruiz-Irastorza G, Khamashta MA, Hunt BJ, Escudero A, Cuadrado MJ, Hughes GR. Bleeding and recurrent thrombosis in definite antiphospholipid syndrome: analysis of a series of 66 patients treated with oral anticoagulation to a target international normalized ratio of 3.5. Arch Intern Med. 2002 May 27;162(10):1164-9. PubMed 12020188
Keeling D, Mackie I, Moore GW, Greer IA, Greaves M; British Committee for Standards in Haematology. Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol. 2012 Apr;157(1):47-58. doi: 10.1111/j.1365-2141.2012.09037.x. Epub 2012 Feb 8. Review. PubMed 22313321Keeling D, Mackie I, Moore GW, Greer IA, Greaves M; British Committee for Standards in Haematology. Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol. 2012 Apr;157(1):47-58. doi: 10.1111/j.1365-2141.2012.09037.x. Epub 2012 Feb 8. Review. PubMed 22313321
Giannakopoulos B, Krilis SA. How I treat the antiphospholipid syndrome. Blood. 2009 Sep 3;114(10):2020-30. doi: 10.1182/blood-2009-05-220756. Epub 2009 Jul 8. Review. PubMed 19587374Giannakopoulos B, Krilis SA. How I treat the antiphospholipid syndrome. Blood. 2009 Sep 3;114(10):2020-30. doi: 10.1182/blood-2009-05-220756. Epub 2009 Jul 8. Review. PubMed 19587374
Les I, Ruiz-Irastorza G, Khamashta MA. Intensity and duration of anticoagulation therapy in antiphospholipid syndrome. Semin Thromb Hemost. 2012 Jun;38(4):339-47. doi: 10.1055/s-0032-1304720. Epub 2012 Mar 30. Review. PubMed 22467528Les I, Ruiz-Irastorza G, Khamashta MA. Intensity and duration of anticoagulation therapy in antiphospholipid syndrome. Semin Thromb Hemost. 2012 Jun;38(4):339-47. doi: 10.1055/s-0032-1304720. Epub 2012 Mar 30. Review. PubMed 22467528
Nayer A, Ortega LM. Catastrophic antiphospholipid syndrome: a clinical review. J Nephropathol. 2014 Jan;3(1):9-17. doi: 10.12860/jnp.2014.03. Epub 2014 Jan 1. Review. PubMed 24644537Nayer A, Ortega LM. Catastrophic antiphospholipid syndrome: a clinical review. J Nephropathol. 2014 Jan;3(1):9-17. doi: 10.12860/jnp.2014.03. Epub 2014 Jan 1. Review. PubMed 24644537
Rosendaal FR, Cannegieter SC, van der Meer FJ, Briët E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost. 1993 Mar 1;69(3):236-9. PubMed 8470047Rosendaal FR, Cannegieter SC, van der Meer FJ, Briët E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost. 1993 Mar 1;69(3):236-9. PubMed 8470047
Cronan JJ. Venous thromboembolic disease: the role of US. Radiology. 1993 Mar;186(3):619-30. Review. PubMed 8430164Cronan JJ. Venous thromboembolic disease: the role of US. Radiology. 1993 Mar;186(3):619-30. Review. PubMed 8430164
Prandoni P, Cogo A, Bernardi E, Villalta S, Polistena P, Simioni P, Noventa F, Benedetti L, Girolami A. A simple ultrasound approach for detection of recurrent proximal-vein thrombosis. Circulation. 1993 Oct;88(4 Pt 1):1730-5. PubMed 8403319Prandoni P, Cogo A, Bernardi E, Villalta S, Polistena P, Simioni P, Noventa F, Benedetti L, Girolami A. A simple ultrasound approach for detection of recurrent proximal-vein thrombosis. Circulation. 1993 Oct;88(4 Pt 1):1730-5. PubMed 8403319
Bates SM, Jaeschke R, Stevens SM, Goodacre S, Wells PS, Stevenson MD, Kearon C, Schunemann HJ, Crowther M, Pauker SG, Makdissi R, Guyatt GH. Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e351S-e418S. doi: 10.1378/chest.11-2299. PubMed 22315267Bates SM, Jaeschke R, Stevens SM, Goodacre S, Wells PS, Stevenson MD, Kearon C, Schunemann HJ, Crowther M, Pauker SG, Makdissi R, Guyatt GH. Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e351S-e418S. doi: 10.1378/chest.11-2299. PubMed 22315267
Stein PD, Gottschalk A, Sostman HD, Chenevert TL, Fowler SE, Goodman LR, Hales CA, Hull RD, Kanal E, Leeper KV Jr, Nadich DP, Sak DJ, Tapson VF, Wakefield TW, Weg JG, Woodard PK. Methods of Prospective Investigation of Pulmonary Embolism Diagnosis III (PIOPED III). Semin Nucl Med. 2008 Nov;38(6):462-70. doi: 10.1053/j.semnuclmed.2008.06.003. Review. PubMed 19331840Stein PD, Gottschalk A, Sostman HD, Chenevert TL, Fowler SE, Goodman LR, Hales CA, Hull RD, Kanal E, Leeper KV Jr, Nadich DP, Sak DJ, Tapson VF, Wakefield TW, Weg JG, Woodard PK. Methods of Prospective Investigation of Pulmonary Embolism Diagnosis III (PIOPED III). Semin Nucl Med. 2008 Nov;38(6):462-70. doi: 10.1053/j.semnuclmed.2008.06.003. Review. PubMed 19331840
PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA. 1990 May 23-30;263(20):2753-9. PubMed 2332918PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA. 1990 May 23-30;263(20):2753-9. PubMed 2332918
van Belle A, Büller HR, Huisman MV, Huisman PM, Kaasjager K, Kamphuisen PW, Kramer MH, Kruip MJ, Kwakkel-van Erp JM, Leebeek FW, Nijkeuter M, Prins MH, Sohne M, Tick LW; Christopher Study Investigators. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA. 2006 Jan 11;295(2):172-9. PubMed 16403929van Belle A, Büller HR, Huisman MV, Huisman PM, Kaasjager K, Kamphuisen PW, Kramer MH, Kruip MJ, Kwakkel-van Erp JM, Leebeek FW, Nijkeuter M, Prins MH, Sohne M, Tick LW; Christopher Study Investigators. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA. 2006 Jan 11;295(2):172-9. PubMed 16403929
Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. PubMed 15842354Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. PubMed 15842354
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