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)
Overview
- Phase
- Phase 3
- Intervention
- Sugammadex
- Conditions
- Neuromuscular Blockade
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 1198
- Primary Endpoint
- Number of Participants With One or More Adjudicated Events of Bleeding (Major or Non-major) With Onset Within 24 Hours After Study Drug Administration
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
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.
Detailed Description
Participants will be randomized to sugammadex or usual care in a 1:1 ratio.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
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.
Intervention: Sugammadex
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.
Intervention: Placebo to neostigmine
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.
Intervention: neostigmine and glycopyrrolate or atropine
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.
Intervention: Placebo to sugammadex
Outcomes
Primary Outcomes
Number of Participants With One or More Adjudicated Events of Bleeding (Major or Non-major) With Onset Within 24 Hours After Study Drug Administration
Time Frame: 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.
Secondary Outcomes
- 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)