Ticagrelor Hemoadsorption Using Cytosorb® for Reduction of Bleeding During Cardiac Surgery (TICAdSORB)
Ticagrelor Hemoadsorption Using Cytosorb® for Reduction of Bleeding During Cardiac Surgery - TICAdSORB
Cardiac surgery is at high risk of intraoperative bleeding. Inhibitors of the P2Y12 platelet receptor, such as ticagrelor, are recommended in patients with acute coronary stroke (ACS) to reduce the incidence of major cardiovascular events. Nevertheless, some patients may require coronary artery bypass graft under cardiac bypass after ticagrelor administration. This administration within 48 hours prior to surgery is associated with a significant increase in bleeding and related poor outcomes, notably because platelet transfusion fails to reverse ticagrelor induced platelet dysfunction. Conversely, waiting several days to plan surgery, in the idea of clearing blood from ticagrelor, exposes to a risk of ischemic recurrence.
Another situation where ticagrelor administration may impend prognosis is emergent aortic surgeries, including aortic dissection or aneurysm rupture. Ticagrelor is frequently administrated because symptoms can mimic ACS, but it may increase bleeding and transfusion by at least 50%.
Several case reports and cohorts described blood hemadsorption, using the Cytosorb® blood purification system (Cytosorb®ents, USA) as a reversal therapy for ticagrelor, reducing bleeding. Cytosorb® is a polymeric beads system with a large exchange surface, enabling the adsorption and removal of molecules of intermediate sizes (< 60 kDa). It has been described to reduce the plasma levels of ticagrelor, with a removal up to 75% after 60 min. It can be connected directly to the heart-lung machine. Its use during cardiac bypass is simple and has not described to induce additional hemolysis.
We hypothesize that the use of Cytosorb® hemoadsorption during cardiac bypass would reduce the incidence of moderate to massive bleeding in patients receiving ticagrelor within 48 hours prior to surgery.
調査の概要
状態
条件
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：BESNIER
- 電話番号：+33232881705
- メール：Emmanuel.Besnier@chu-rouen.fr
研究場所
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Rouen、フランス
- CHU de Rouen
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コンタクト：
- BESNIER
- 電話番号：+33232881705
- メール：Emmanuel.Besnier@chu-rouen.fr
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主任研究者：
- BESNIER
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-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Patient or patient's representative having read and understood the information letter and signed the consent form
- Age ≥ 18 y/o
- Ticagrelor administration within 48 hours prior to surgery
- Cardiac surgery with cardiac bypass
- Patient affiliated with, or beneficiary of a social security (health insurance) category.
Women of childbearing potential (a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile):
- with effective contraception (Cf. CTCG) (progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action, male or female condom with or without spermicide, cap, diaphragm or sponge with spermicide) since 1 month, during study period
- negative blood pregnancy test by b-HCG at inclusion.
- Women permanently sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy)
- Postmenopausal women: A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
Exclusion Criteria:
- Concomitant antiplatelet drugs or ongoing anticoagulants other than aspirin and heparin
- Ongoing systemic infection (including active endocarditis)
- Ongoing treatment with an antibiotic or antifungal at high risk of removal by Cytosorb®: teicoplanin, vancomycin, linezolid, gentamycin, amphotericin B liposomal, azole drugs or fluconazole
- Ongoing treatment with an anticonvulsant at high risk of removal by Cytosorb®: phenytoin, phenobarbital or valproic acid.
- Contraindications to Cytosorb® (known preoperative platelet count < 20 000/mm3, Sickle cell disease crisis, history to heparin-induced thrombopenia, body mass index ≥ 40 kg/m², hypersensitivity to a component, Any pre-existing contraindication to extracorporeal therapy (CPB))
- Cardiac surgery for ventricle assistance device or transplantation
- Preoperative critical state
- Chronic pathology with life expectancy less than 1 month
- Pregnant or breastfeeding women and women of child-bearing age not using effective means of contraception
- Absence of affiliation to a social security program
- Person deprived of liberty by an administrative or judiciary decision or person placed under judicial protection, under guardianship or supervision
- Person consenting to the research participating having participated to another trial within a period of one week
- Person participating to another interventional research
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：実験アーム
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The Cytosorb® hemoadsorption cartridge is inserted into the cardiopulmonary bypass circuit immediately after the blood pump, with blood returned to the venous reservoir.
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偽コンパレータ：control arm
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A sham tubing line, made of the same polymer and with the same diameter as the Cytosorb® tubing, is connected at the same location in the cardiopulmonary bypass circuit without a hemoadsorption cartridge.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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benefit of Cytosorb® in reducing perioperative bleeding of cardiac surgery
時間枠：within the 48 first hours post-CPB
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Incidence of a moderate, severe or massive bleeding defined by an UDPB (Universal Definition for Perioperative Bleeding) score ≥ 2/4 within the 48 first hours post-CPB.
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within the 48 first hours post-CPB
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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compare the distribution of bleeding severity between groups
時間枠：48 hours after surgery
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Bleeding severity categorized according to the four-level UDPB classification within 48 hours post-CPB
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48 hours after surgery
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compare the intensity of intraoperative bleeding
時間枠：48 hours after surgery
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The validated intraoperative bleeding severity scale defined by Lewis et al (Surgery 2017, doi: 10.1016/j.surg.2016.09.022) The Lewis bleeding severity scale is scored based on visual assessment as follows: 0 = no bleeding
Based on qualitative description, it ranges from 0 (no bleeding) to 4 (life-threatening bleeding). Based on visually estimated rate of blood loss (mL/min), it is scored from 0 (≤1 mL/min) to 4 (>50 mL/min). Although the scale includes four subscales, a single overall subjective score ranging from 0 to 4 is assigned based on the combined interpretation of all subscales. |
48 hours after surgery
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compare the surgical reintervention rate due to bleeding between groups
時間枠：90 days
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A surgical reintervention for any cause will be considered within 90 days.
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90 days
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compare between groups, the risk of other hemorrhagic complications
時間枠：90 days
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Other hemorrhagic complications, including intracranial
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90 days
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compare between groups the risk of major adverse cardiovascular events
時間枠：90 days
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The Major adverse cardiovascular events is defined as the composite outcome of myocardial infarction, cerebral stroke, acute heart failure, death
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90 days
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compare between groups, the risk of any complication in the composite outcome of acute kidney injury
時間枠：90 days
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AKI will be defined as KDIGO ≥ 1; Acute respiratory failure will be defined by prolonged mechanical ventilation > 12 hours, reintubation, non-invasive ventilatory support or high flow nasal cannula therapy;Infection, sepsis and septic shock, will be defined by the 2026 surviving sepsis campaign
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90 days
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compare quality of life between groups
時間枠：90 days
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The EQ-5D-5L has 5 items with 5 likert levels leading to a score between 0% and 100% based on a specific population-dependent algorithm Higher scores indicate better quality of life (100% = very good health)
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90 days
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Red blood cell transfusion at 90 days
時間枠：Baseline to 90 days
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Total number of red blood cell (RBC) units transfused within 90 days after baseline.
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Baseline to 90 days
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Fresh frozen plasma transfusion at 90 days
時間枠：Baseline to 90 days
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Total number of fresh frozen plasma (FFP) units transfused within 90 days after baseline.
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Baseline to 90 days
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Prothrombin complex concentrate use at 90 days
時間枠：Baseline to 90 days
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Total dose of Prothrombin Complex Concentrate (PCC) administered within 90 days after baseline, reported in international units (IU).
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Baseline to 90 days
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Platelet transfusion at 90 days
時間枠：Baseline to 90 days
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Total number of platelet units transfused within 90 days after baseline.
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Baseline to 90 days
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Fibrinogen concentrate administration at 90 days
時間枠：Baseline to 90 days
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Total dose of fibrinogen concentrate administered within 90 days after baseline, reported in grams (g).
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Baseline to 90 days
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Activated factor VII administration at 90 days
時間枠：Baseline to 90 days
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Total dose of activated factor VII administered within 90 days after baseline, reported in grams (g).
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Baseline to 90 days
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協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- 2023/0300/HP
- 2025-A02958-41 (レジストリ識別子：RCB)
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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