Dabigatran vs. Oral Anti-Xa Inhibitors in S. Aureus Bacteremia
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 300
- 试验地点
- 2
- 主要终点
- Desirability of Outcome Ranking (DOOR)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participant must meet all inclusion and
排除标准
- •for the SNAP Platform (NCT05137119) and also the following inclusion and exclusion criteria:
- •Inclusion Criteria:
- •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.
- •Exclusion Criteria:
- •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)
研究组 & 干预措施
Continue current anticoagulant
Patients will continue their currently prescribed apixaban, edoxaban, or rivaroxaban
干预措施: Rivaroxaban (Drug)
Change to Dabigatran
Patients will have their anticoagulation changed to dabigatran at the monograph approved dose for the indication, bleeding risk, and renal function.
干预措施: Dabigatran (Drug)
Continue current anticoagulant
Patients will continue their currently prescribed apixaban, edoxaban, or rivaroxaban
干预措施: Apixaban (Drug)
Continue current anticoagulant
Patients will continue their currently prescribed apixaban, edoxaban, or rivaroxaban
干预措施: edoxaban (Drug)
结局指标
主要结局
Desirability of Outcome Ranking (DOOR)
时间窗: Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)
Desirability of Outcome Ranking (DOOR) - an ordinal outcome with 5 levels defined: Rank 1 - Alive without complication Rank 2 - Alive with 1 complication Rank 3 - Alive with 2 complications Rank 4 - Alive with 3 complications Rank 5 - Dead Complications include: 1. Clinical failure: Absence of resolution of clinical signs and symptoms of S. aureus bacteremia such that no additional antibiotic therapy is required or anticipated. 2. Infectious Complications: Including new endocarditis; new evidence of other deep metastatic foci (e.g., osteomyelitis or deep abscess); relapse of MRSA bacteremia after a patient has sterilized their initial blood cultures; readmission for subsequent care of S. aureus bacteremia; need for unplanned source control procedures 3. Serious adverse drug event (Common Terminology Criteria class 4) due to study drug OR adverse drug event (classes 1-3) leading to discontinuation of the study drug
次要结局
- Clinical failure(Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119))
- Serious Adverse Event or Adverse Event Leading to Discontinuation(Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119))
- All cause mortality(Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119))
- Infectious Complications(Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119))
- Clinically relevant major bleeding(Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119))
- Clinically relevant venous thromboembolic events(Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119))
- Clinically relevant stroke(Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119))
- Clinically relevant acute myocardial infarction(Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119))
- Clinically relevant arterial thromboembolic event(Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119))
研究者
Emily McDonald
Associate Professor of Medicine and Staff Scientist
McGill University Health Centre/Research Institute of the McGill University Health Centre