Clinical trial NCT01422304: Reversal of Neuromuscular Blockade With Sugammadex or Usual Care in Hip Fracture Surgery or Joint (Hip/Knee) Replacement (P07038)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neuromuscular Blockade
Arthroplasty, Replacement, Hip
Arthroplasty, Replacement, Knee
Blood Coagulation
Antithrombotic Agents
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-08-23
Enrollment: 1198
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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
* Must be:

  * 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
* 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

Primary outcomes:
measure: Number of Participants With One or More Adjudicated Events of Bleeding (Major or Non-major) With Onset Within 24 Hours After Study Drug Administration
timeFrame: Up to 24 hours post study drug administration
Secondary outcomes:
measure: Percent Change From Baseline in Activated Partial Thromboplastin Time (aPTT) at 10 and 60 Minutes Post Study Drug Administration
timeFrame: Baseline, 10 and 60 minutes post study drug administration
measure: Percent Change From Baseline in Prothrombin Time (International Normalized Ratio) (PT[INR]) at 10 and 60 Minutes Post Study Drug Administration
timeFrame: Baseline, 10 and 60 minutes post study drug administration
measure: Number of Participants With One or More Adjudicated Events of Bleeding (Major or Non-major) With Onset Within 14 Days After Study Drug Administration
timeFrame: Up to 14 days post study drug administration
measure: Number of Participants With One or More Adjudicated Major Events of Bleeding With Onset Within 24 Hours After Study Drug Administration
timeFrame: Up to 24 hours post study drug administration
measure: Number of Participants With One or More Adjudicated Major Events of Bleeding With Onset Within 14 Days After Study Drug Administration
timeFrame: Up to 14 days post study drug administration
measure: Number of Participants With One or More Adjudicated Venous Thromboembolic (VTE) Events With Onset Within 14 Days After Study Drug Administration
timeFrame: Up to 14 days post study drug administration
measure: Number of Participants With One or More Adjudicated Events of Anaphylaxis With Onset Within 14 Days After Study Drug Administration
timeFrame: Up to 14 days post study drug administration
Other outcomes:
measure: Postoperative Drainage Volume Within 24 Hours After Study Drug Administration
timeFrame: Up to 24 hours post study drug administration
measure: Number of Participants Requiring Any Postoperative Transfusion
timeFrame: From end of study drug administration through approximately 120 hours after study drug administration
measure: Total Transfusion Volume in Participants Who Required Postoperative Transfusion
timeFrame: From end of study drug administration through approximately 120 hours after study drug administration
measure: Postoperative Changes in Hgb Concentrations Using the Bleeding Index
timeFrame: Baseline and Visit 3 (24-48 hours post study drug administration)
measure: Number of Participants With One or More Postoperative Anemia Adverse Events With Onset Within 72 Hours After Study Drug Administration
timeFrame: Up to 72 hours post study drug administration
Locations:
Study officials:
References:
citation: Rahe-Meyer N, Fennema H, Schulman S, Klimscha W, Przemeck M, Blobner M, Wulf H, Speek M, McCrary Sisk C, Williams-Herman D, Woo T, Szegedi A. Effect of reversal of neuromuscular blockade with sugammadex versus usual care on bleeding risk in a randomized study of surgical patients. Anesthesiology. 2014 Nov;121(5):969-77. doi: 10.1097/ALN.0000000000000424.