Dabigatran vs. Oral Anti-Xa Inhibitors in S. Aureus Bacteremia

Обзор

This is an open-label randomized controlled trial which will enroll patients with S. aureus bacteremia who are already taking oral anticoagulant medications (apixaban, edoxaban, or rivaroxaban) for an approved indication (stroke prevention in atrial fibrillation, prevention or treatment of venous thromboembolism). We will randomize patients to continue their existing medication or change to another medication (dabigatran) which is approved for the original indication. Dabigatran is approved in many countries for the treatment or prevention of venous thromboembolism or preventing stroke in atrial fibrillation. Unlike the other medications listed above, dabigatran seems to have activity against S. aureus in the test tube, in animal models, and in a smaller randomized controlled trial. We wish to determine if changing to dabigatran will improve outcomes in S. aureus bacteremia in people who otherwise would have a reason to be taking it. This study is an approved sub-study of The Staphylococcus aureus Network Adaptive Platform (SNAP) trial (NCT05137119). If positive, this study will support a second RCT in people who do not currently have an indication for anticoagulation.

Вмешательства

• Препарат Dabigatran
  Patients will be assigned to change to dabigatran at the monograph approved dose for their indication, bleeding risk, and renal function.
• Препарат Apixaban
  Patients will continue taking their currently prescribed apixaban, edoxaban, or rivaroxaban
• Препарат edoxaban
  Patients will continue taking their currently prescribed apixaban, edoxaban, or rivaroxaban
• Препарат Rivaroxaban
  Patients will continue taking their currently prescribed apixaban, edoxaban, or rivaroxaban

Первичные конечные точки

• Desirability of Outcome Ranking (DOOR) [Срок оценки: Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)]

Вторичные конечные точки (9)

• Clinical failure [Срок оценки: Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)]
• Serious Adverse Event or Adverse Event Leading to Discontinuation [Срок оценки: Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)]
• All cause mortality [Срок оценки: Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)]
• Infectious Complications [Срок оценки: Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)]
• Clinically relevant major bleeding [Срок оценки: Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)]
• Clinically relevant venous thromboembolic events [Срок оценки: Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)]
• Clinically relevant stroke [Срок оценки: Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)]
• Clinically relevant acute myocardial infarction [Срок оценки: Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)]
• Clinically relevant arterial thromboembolic event [Срок оценки: Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)]

Критерии участия

The participant must meet all inclusion and exclusion criteria for the SNAP Platform (NCT05137119) and also the following inclusion and exclusion criteria:

Критерии включения

• Patient is taking (or will imminently start taking) an oral Xa inhibitor (e.g., apixaban, edoxaban, rivaroxaban) for: stroke prevention in atrial fibrillation, treatment or secondary prevention of deep venous thrombosis or pulmonary embolism, prevention of VTE in patients who have undergone elective total hip or total knee replacement surgery provided there are 30 or more days of planned treatment remaining at the time of enrolment.

Критерии исключения

• Active bleeding as determine by the site investigator after discussion with the treating team (patient may remain eligible for up to 120 hours from platform entry if condition is resolved and antithrombotic therapy is resumed)
• Anticipated major cardiac surgery, neurosurgery, or spine surgery within the next 3 days
• Known pregnancy (with testing available for women with childbearing potential)
• Known use of dabigatran within last month
• Allergy to dabigatran
• Concomitant use of amiodarone, ketoconazole, rifampin, verapamil, clopidogrel, prasugrel, or ticagrelor
• eGFR < 30mL/minute calculated by Cockcroft-Gault equation using adjusted weight \[patient may remain eligible for up to 120 hours from platform entry if acute kidney injury is resolved such that antithrombotic therapy can be safely resumed/prescribed\]
• Off label use (e.g., metallic mechanical heart valve, left ventricular thrombus, antiphospholipid antibody syndrome)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• McGill University Health Centre (Royal Victoria Hospital and Montreal General Hospital) — Montreal

Публикации

• Lerche CJ, Christophersen LJ, Goetze JP, Nielsen PR, Thomsen K, Enevold C, Hoiby N, Jensen PO, Bundgaard H, Moser C. Adjunctive dabigatran therapy improves outcome of experimental left-sided Staphylococcus aureus endocarditis. PLoS One. 2019 Apr 19;14(4):e0215333. doi: 10.1371/journal.pone.0215333. eCollection 2019. PMID 31002679
• Butt JH, Fosbol EL, Verhamme P, Gerds TA, Iversen K, Bundgaard H, Bruun NE, Larsen AR, Petersen A, Andersen PS, Skov RL, Gislason GH, Torp-Pedersen C, Kober L, Olesen JB. Dabigatran and the Risk of Staphylococcus aureus Bacteremia: A Nationwide Cohort Study. Clin Infect Dis. 2021 Aug 2;73(3):480-486. doi: 10.1093/cid/ciaa661. PMID 32478836
• Vanassche T, Verhaegen J, Peetermans WE, VAN Ryn J, Cheng A, Schneewind O, Hoylaerts MF, Verhamme P. Inhibition of staphylothrombin by dabigatran reduces Staphylococcus aureus virulence. J Thromb Haemost. 2011 Dec;9(12):2436-46. doi: 10.1111/j.1538-7836.2011.04529.x. PMID 22040101
• Vanassche T, Verhaegen J, Peetermans WE, Hoylaerts MF, Verhamme P. Dabigatran inhibits Staphylococcus aureus coagulase activity. J Clin Microbiol. 2010 Nov;48(11):4248-50. doi: 10.1128/JCM.00896-10. Epub 2010 Sep 1. PMID 20810780
• Peetermans M, Liesenborghs L, Peerlinck K, Wijngaerden EV, Gheysens O, Goffin KE, Hoylaerts MF, Jacquemin M, Verhaegen J, Peetermans WE, Verhamme P, Vanassche T; Staphylothrombin Investigators. Targeting Coagulase Activity in Staphylococcus aureus Bacteraemia: A Randomized Controlled Single-Centre Trial of Staphylothrombin Inhibition. Thromb Haemost. 2018 May;118(5):818-829. doi: 10.1055/s-0038-16 PMID 29614521
• Tong SYC, Mora J, Bowen AC, Cheng MP, Daneman N, Goodman AL, Heriot GS, Lee TC, Lewis RJ, Lye DC, Mahar RK, Marsh J, McGlothlin A, McQuilten Z, Morpeth SC, Paterson DL, Price DJ, Roberts JA, Robinson JO, van Hal SJ, Walls G, Webb SA, Whiteway L, Yahav D, Davis JS; Staphylococcus aureus Network Adaptive Platform (SNAP) Study Group. The Staphylococcus aureus Network Adaptive Platform Trial Protocol: PMID 35717634
• McDonald EG, Cheng MP, Davis JS, Goodman AL, Lawler PR, Marsh J, Mertz D, Paul M, Rodriguez-Bano J, Siegal DM, Tong SY, Walls G, Lee TC; SNAP Global Trial Steering Committee. Is there a role for anticoagulation with dabigatran in S. aureus bacteremia? Protocol for the adjunctive treatment domain of the Staphylococcus aureus Network Adaptive Platform (SNAP) randomised controlled trial. BMJ Open. 20 PMID 41387009

Идентификаторы

NCT: NCT06650501 · 2025-10900 · 500464

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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