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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 August 24, 2021) 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 Identification, Study Description, Eligibility and Conditions
12 August 24, 2021 Study Status
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, Oversight, Study Description, Study Design, Arms and Interventions, Eligibility, Contacts/Locations and IPDSharing
Open or close this module 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:
Open or close this module Study Status
Record Verification: November 2014 June 2017
Overall Status: Not yet recruitingRecruiting
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]
Open or close this module Sponsor/Collaborators
Sponsor: Intermountain Health Care, Inc. Intermountain Health Care, Inc.
Responsible Party: Sponsor Sponsor
Collaborators: Bristol-Myers Squibb Bristol-Myers Squibb
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes Yes
Open or close this module 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 ]

Open or close this module Conditions
Conditions: Antiphospholipid Syndrome
Thrombosis 		Antiphospholipid Syndrome
Thrombosis
Keywords:
Open or close this module 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]
Open or close this module 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.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Rate of Thrombosis (arterial and/or venous)
[ Time Frame: Up to 13 months after enrollment ]

 Rate of Thrombosis (arterial and/or venous)
[ Time Frame: Up to 13 months after enrollment ]
2. Major and non-major bleeding
[ Time Frame: Up to 13 months after enrollment ]

 Major and non-major bleeding
[ Time Frame: Up to 13 months after enrollment ]
Open or close this module 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.

Open or close this module Contacts/Locations
Central Contact Person: 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:Contact: Shauna Bruun 801-408-2137 Shauna.Bruun@imail.org
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
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