A Randomized, Controlled, Parallel-group, Double-blind Trial of Sugammadex or Usual Care (Neostigmine or Spontaneous Recovery) for Reversal of Rocuronium- or Vecuronium-induced Neuromuscular Blockade in Patients Receiving Thromboprophylaxis and Undergoing Hip Fracture Surgery or Joint (Hip/Knee) Replacement (Protocol No. P07038)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,198
- 主要终点
- Number of Participants With One or More Adjudicated Events of Bleeding (Major or Non-major) With Onset Within 24 Hours After Study Drug Administration
研究概览
简要总结
This study will assess the effect of reversal of neuromuscular blockade with sugammadex compared with reversal according to usual care (neostigmine or spontaneous reversal) on the incidence of post-surgical bleeding events and on coagulation parameters in participants undergoing hip fracture surgery or joint (hip/knee) replacement surgery with neuromuscular blockage induced by rocuronium or vecuronium.
详细描述
Participants will be randomized to sugammadex or usual care in a 1:1 ratio.
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
- Triple (Participant, Investigator, 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
- •Must be American Society of Anesthesiologists (ASA) Class 1, 2, or 3
- •Must be scheduled for a hip fracture surgery or joint (hip or knee) replacement surgery under general anesthesia including the use of rocuronium or vecuronium for neuromuscular blockade
- •Currently receiving thromboprophylactic (anti-clotting) therapy with low molecular weight heparin (LMWH) or unfractionated heparin (UFH), or
- •Planned to initiate thromboprophylactic therapy with LMWH or UFH prior to or during surgery, or
- •Currently receiving ongoing thromboprophylactic therapy with a vitamin K antagonist that has been temporarily substituted with peri-operative LMWH or UFH, and/or
- •Currently receiving ongoing thromboprophylactic therapy with low-dose aspirin or other antiplatelet therapy
- •Platelet count above the lower limit of normal range
- •Appropriate candidate for rapid reversal of neuromuscular blockade
- •Sexually active females must agree to use a medically accepted method of contraception through seven days after receiving protocol-specified medication
排除标准
- •Anatomical malformations that may lead to difficult intubation
- •Neuromuscular disorder that may affect neuromuscular blockade
- •History of a coagulation disorder, bleeding diathesis, systemic lupus erythematosus or antiphospholipid syndrome
- •History or evidence of active abnormal bleeding or blood clotting within 30 days prior to screening
- •Significant hepatic dysfunction
- •Severe renal insufficiency
- •History or family history of malignant hyperthermia
- •Hypersensitivity or hypersensitivity-like reaction to sugammadex, muscle relaxants, or other medications used during general anesthesia
- •Planned intravenous administration of toremifene and/or fusidic acid within 24 hours before or within 24 hours after study medication
- •Recent, severe trauma
- •Body Mass Index (BMI) > 35
- •Any contraindication to administration of sugammadex or neostigmine/glycopyrrolate (or neostigmine/atropine)
- •Pregnant or intends to become pregnant between randomization and the Day 30 follow-up visit
- •Breast-feeding
- •Previously treated with sugammadex or participated in a sugammadex clinical trial
- •Has an active hip/knee infection and is scheduled for revision surgery
研究组 & 干预措施
Sugammadex
Prior to randomization, participants will be assigned to planned active reversal or planned spontaneous recovery by the anesthesiologist according to the recovery method the anesthesiologist would have chosen if the participant were not in the study. In this treatment arm, participants assigned to planned active reversal will receive sugammadex and placebo to neostigmine, and participants assigned to planned spontaneous recovery will receive sugammadex. Study drug will be administered after the last dose of rocuronium or vecuronium and after wound closure.
干预措施: Sugammadex (Drug)
Sugammadex
Prior to randomization, participants will be assigned to planned active reversal or planned spontaneous recovery by the anesthesiologist according to the recovery method the anesthesiologist would have chosen if the participant were not in the study. In this treatment arm, participants assigned to planned active reversal will receive sugammadex and placebo to neostigmine, and participants assigned to planned spontaneous recovery will receive sugammadex. Study drug will be administered after the last dose of rocuronium or vecuronium and after wound closure.
干预措施: Placebo to neostigmine (Drug)
Usual Care
Prior to randomization, participants will be assigned to planned active reversal or planned spontaneous recovery by the anesthesiologist according to the recovery method the anesthesiologist would have chosen if the participant were not in the study. In this treatment arm, participants assigned to planned active reversal will receive neostigmine and placebo to sugammadex, and participants assigned to planned spontaneous recovery will receive placebo to sugammadex. Study drug will be administered after the last dose of rocuronium or vecuronium and after wound closure.
干预措施: neostigmine and glycopyrrolate or atropine (Drug)
Usual Care
Prior to randomization, participants will be assigned to planned active reversal or planned spontaneous recovery by the anesthesiologist according to the recovery method the anesthesiologist would have chosen if the participant were not in the study. In this treatment arm, participants assigned to planned active reversal will receive neostigmine and placebo to sugammadex, and participants assigned to planned spontaneous recovery will receive placebo to sugammadex. Study drug will be administered after the last dose of rocuronium or vecuronium and after wound closure.
干预措施: Placebo to sugammadex (Drug)
结局指标
主要结局
Number of Participants With One or More Adjudicated Events of Bleeding (Major or Non-major) With Onset Within 24 Hours After Study Drug Administration
时间窗: Up to 24 hours post study drug administration
Post-treatment events of bleeding were evaluated by a medically-qualified, blinded member of the surgical team (Blinded Safety Assessor), in consultation with the surgeon, to determine if an event was a "suspected, unanticipated adverse event of bleeding" (SUAEB). A SUAEB is an event of bleeding outside the usual boundaries of expectations for a participant (e.g., in amount of blood lost, prolonged duration of bleeding, or other factors) considering the type of procedure as well as participant's specific surgical experience and underlying risk of bleeding. In addition, blinded review of clinical and laboratory databases was performed to identify any event potentially consistent with a SUAEB; these were reviewed by the Blinded Safety Assessor, who determined if any was a SUAEB. All SUAEBs were evaluated by a blinded external Adjudication Committee, which classified each as either: 1) a major bleeding event, 2) a non-major bleeding event, or 3) not an unanticipated event of bleeding.
次要结局
- Percent Change From Baseline in Prothrombin Time (International Normalized Ratio) (PT[INR]) at 10 and 60 Minutes Post Study Drug Administration(Baseline, 10 and 60 minutes post study drug administration)
- Number of Participants With One or More Adjudicated Events of Bleeding (Major or Non-major) With Onset Within 14 Days After Study Drug Administration(Up to 14 days post study drug administration)
- Number of Participants With One or More Adjudicated Major Events of Bleeding With Onset Within 24 Hours After Study Drug Administration(Up to 24 hours post study drug administration)
- Percent Change From Baseline in Activated Partial Thromboplastin Time (aPTT) at 10 and 60 Minutes Post Study Drug Administration(Baseline, 10 and 60 minutes post study drug administration)
- Number of Participants With One or More Adjudicated Major Events of Bleeding With Onset Within 14 Days After Study Drug Administration(Up to 14 days post study drug administration)
- Number of Participants With One or More Adjudicated Venous Thromboembolic (VTE) Events With Onset Within 14 Days After Study Drug Administration(Up to 14 days post study drug administration)
- Number of Participants With One or More Adjudicated Events of Anaphylaxis With Onset Within 14 Days After Study Drug Administration(Up to 14 days post study drug administration)