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Antiphospholipid SyndromePhase 4ASTRO-APSNCT02295475

Apixaban for Secondary Prevention of Thromboembolism Among Patients With AntiphosPholipid Syndrome

A Phase 4 study testing Apixaban and Warfarin in people with Antiphospholipid Syndrome and Thrombosis, run by Scott C. Woller, MD at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study is designed to compare the safety and effectiveness of two blood thinners, apixaban and warfarin, for the prevention of blood clots in patients who have a higher risk of blood clots than the general population, a condition called "antiphospholipid syndrome". Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Antiphospholipid Syndrome, Thrombosis
What is being tested?
Apixaban and Warfarin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
2 sitesUnited States
Study dates
10 Dec 2014to Mar 2022
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Be ≥ 18 years of age
  • Have a clinical diagnosis of the antiphospholipid syndrome (APS) and a history of venous thrombosis only (excluding arterial thrombosis as recommended by the Data Safety Monitoring Board (DSMB)) for which the patient is receiving anticoagulation therapy for the prevention of recurrent thrombosis;
  • Anticoagulation is defined as warfarin sodium titrated at the discretion of the clinician to a target INR (International Normalized Ratio) 2.5 (range 2-3), 3.0 (range 2.5-3.5), or 3.5 (range 3-4).
  • Should the patient be receiving some other form of anticoagulation (apixaban, rivaroxaban, edoxaban, dabigatran etexilate, low-molecular weight heparin) and is willing to be randomized to warfarin with a target INR 2.5 or apixaban 5 mg by mouth twice daily and meets all other inclusion criteria.
  • Able to undergo magnetic resonance imaging (MRI) of the brain;
  • Have completed at least 6 months of anticoagulation for the indication of venous thrombosis and be without symptoms or signs consistent with acute thrombosis for a minimum of 6 months;
Show all 13Show fewer
  • Be willing to provide informed consent to contact the subjects anticoagulation provider for INRs and dosing as well as details regarding any adverse events;
  • A woman of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of hCG (Human Chorionic Gonadotropin) within 24 hours prior to the start of study drug;
  • Women must not be breastfeeding;
  • A 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;
  • Males who are sexually active with any 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;
  • Azoospermic males and women who are continuously not heterosexually active are exempt from contraceptive requirements. However, a WOCBP must still undergo pregnancy testing as described above;
  • If they are actively receiving a strong dual inhibitor of cytochrome P450 3A4 (CYP3A4) and P-gp, such as ketoconazole, itraconazole, ritonavir, and are agreeable to taking apixaban 2.5 mg twice daily.

Who cannot join

  • A history of arterial thromboembolism (e.g., stroke, myocardial infarction, or other arterial thrombosis);
  • Another indication for long-term anticoagulation for which no FDA (Food \& Drug Administration) approval of apixaban exists (e.g., mechanical heart valve);
  • A life expectancy of less than 1 year;
  • Is unable to attend follow-up appointments;
  • Is participating in a clinical trial or has participated in a trial within the last 30 days;
  • Is receiving concomitant dual antiplatelet therapy;
Show all 26Show fewer
  • Requires aspirin dose of greater than 165 mg daily;
  • Requires clopidogrel, ticagrelor, prasugrel, or another P2Y12 inhibitor;
  • A hemoglobin level of less than 8 mg per deciliter;
  • A platelet count of less than 50,000 per cubic millimeter;
  • Serum creatinine level of more than 2.5 mg per deciliter or a calculated creatinine clearance of less than 25 ml per minute;
  • Alanine aminotransferase or aspartate aminotransferase level greater than 2 times the upper limit of the normal range;
  • A total bilirubin more than 1.5 times the upper limit of the normal range;
  • Have active cancer for which treatment (chemotherapy/radiation therapy) is being delivered or has been delivered within the last 3 months;
  • Are actively taking a strong dual inducer of CYP3A4 and P-gp, such as:
  • rifampin
  • carbamazepine
  • phenytoin
  • St.John's wort
  • Intend pregnancy or breastfeeding within the next year;
  • Have a known allergy to apixaban, rivaroxaban, or edoxaban;
  • Have experienced thrombosis while receiving warfarin at a target INR of 2 to 3 and have been assigned a higher target INR at the discretion of the treating clinician;
  • Have active pathological bleeding;
  • Have a history of catastrophic APS (CAPS) as defined by clinical routine;
  • At the discretion of the investigator, are not considered to be good candidates secondary to a safety concern.
  • Patients who meet the above inclusion \& exclusion criteria will be offered participation in the study. After informed consent is obtained, the patient will be consented for Magnetic Resonance Imaging (MRI). A brain MRI without contrast including weighted imaging and fluid-attenuated inversion recovery (FLAIR) will be performed as a study procedure to rule out prior stroke. If the patient has radiographic evidence of prior stroke on this MRI, then the patient will not be randomized, and will not be included in future study procedures or study analyses.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • The James Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Intermountain Medical Center

    Murray, Utah, 84107

Other trials in United States

About this study

Official title: Apixaban for the Secondary Prevention of Thromboembolism: a Prospective Randomized Outcome Pilot Study Among Patients With the AntiphosPholipid Syndrome

This study is designed to compare the safety and effectiveness of two blood thinners, apixaban and warfarin, for the prevention of blood clots in patients who have a higher risk of blood clots than the general population, a condition called "antiphospholipid syndrome".

Read the detailed description

This study is a prospective, open-label, blinded event, pilot study that will randomize patients with a history of venous thrombosis and antiphospholipid syndrome (APS) already receiving anticoagulation to either warfarin or apixaban. The study will assess the safety and efficacy of apixaban compared with adjusted dose warfarin for the prevention of recurrent thrombosis (defined as the aggregate of arterial or venous thrombosis) and vascular death. The primary efficacy outcome will be confirmed upon adjudication by a panel blinded to the treatment arm. The primary safety outcome will be major bleeding and clinically relevant non-major bleeding events. Patients who consent to study participation will be randomized to anticoagulation with adjusted dose warfarin sodium or apixaban 5 mg by mouth twice daily. This pilot study will also provide information and experience identifying, recruiting, enrolling and randomizing patients with APS and a history of venous thrombosis to anticoagulation with apixaban or warfarin for the prevention of recurrent thrombosis.

Being tested
Apixaban, Warfarin
Keywords
Apixaban, Eliquis
Medical subject headings
Antiphospholipid Syndrome, Thrombosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02295475
Study groupRoleWhat they receive
ApixabanExperimentalSubjects will receive apixaban 5 mg tablets taken twice daily for the duration of the study.
Receives: Drug: Apixaban
WarfarinActive comparatorSubjects will receive warfarin for the duration of the study, with the dose and frequency adjusted per clinician discretion to achieve an INR (International Normalized Ratio) between 2 and 4.
Receives: Drug: Warfarin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate (number divided by duration) of clinically overt thromboses (arterial and/or venous) or vascular death

    Measured: From time of first dose of study drug through 2 days after receiving the last dose of study drug at the end of 12 months of treatment

  2. Rate (number divided by duration) of occurrence of major (including fatal) and clinically relevant non-major bleeding

    Major bleeding is clinically overt bleeding accompanied by one or more of the following: a decrease in the hemoglobin level of 2 g per deciliter or more, transfusion of 2 or more units of packed red cells, bleeding at a critical site (intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, or retroperitoneal), or fatal bleeding. Clinically relevant non-major bleeding is defined as clinically overt bleeding that does not satisfy the criteria for major bleeding and that led to hospital admission, physician-guided medical or surgical treatment, or a change in antithrombotic therapy.

    Measured: From time of first dose of study drug through 2 days after receiving the last dose of study drug at the end of 12 months of treatment

Secondary outcomes (1)

  1. Net clinical benefit (combination of occurrence of thrombosis and bleeding rates)

    Sum of number of thrombosis and bleeding events divided by duration

    Measured: From time of first dose of study drug through 2 days after receiving the last dose of study drug at the end of 12 months of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Nov 2014 (estimated)
  2. Study start10 Dec 2014
  3. Primary completionApr 2020
  4. Study completionMar 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02295475
Sponsor's protocol ID
CV185-357
Other IDs
1040354
Acronym
ASTRO-APS
Status last verified
Sep 2023
First submitted
18 Nov 2014
Last updated
28 Sep 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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. doi: 10.1111/j.1538-7836.2006.01753.x.

    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 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 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 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 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 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 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.

    PubMed 20353992

  • Alarcon-Segovia D, Perez-Vazquez 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. doi: 10.1016/0049-0172(92)90021-5.

    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 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. doi: 10.1016/0002-9343(94)90108-2.

    PubMed 8304360

  • Cervera R, Serrano R, Pons-Estel GJ, Ceberio-Hualde L, Shoenfeld Y, de Ramon 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, Quere I, Hachulla E, Vasconcelos C, Fernandez-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. doi: 10.1182/blood-2002-11-3334. Epub 2003 Jun 19. No abstract available.

    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. doi: 10.1161/CIRCULATIONAHA.107.187998. Epub 2007 Dec 17. No abstract available.

    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. doi: 10.1056/NEJMoa035241.

    PubMed 13679527

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Apixaban and Warfarin in people with Antiphospholipid Syndrome and Thrombosis, run by Scott C. Woller, MD at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate (number divided by duration) of clinically overt thromboses (arterial and/or venous) or vascular death (time frame: From time of first dose of study drug through 2 days after receiving the last dose of study drug at the end of 12 months of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02295475, which also lists 39 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2023.

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