Reversal of Neuromuscular Blockade With Sugammadex or Usual Care in Hip Fracture Surgery or Joint (Hip/Knee) Replacement (P07038)

NCT01422304 | Completed Phase 3 Results DMC

• 3 other identifiers: P070382011-001201-27MK-8616-059
• Study Type: interventional
• Target: 1,198
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Neuromuscular Blockade; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Blood Coagulation; Antithrombotic Agents

Outcome Measures

Primary Outcomes (1)

• Number of Participants With One or More Adjudicated Events of Bleeding (Major or Non-major) With Onset Within 24 Hours After 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.

  Up to 24 hours post study drug administration

Secondary Outcomes (7)

• 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

• 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

• 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

Other Outcomes (5)

• Postoperative Drainage Volume Within 24 Hours After Study Drug Administration

  Up to 24 hours post study drug administration

• Number of Participants Requiring Any Postoperative Transfusion

  From end of study drug administration through approximately 120 hours after study drug administration

• Total Transfusion Volume in Participants Who Required Postoperative Transfusion

  From end of study drug administration through approximately 120 hours after study drug administration

Study Arms (2)

Sugammadex

EXPERIMENTAL

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.

Drug: Sugammadex; Drug: Placebo to neostigmine

Usual Care

EXPERIMENTAL

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.

Drug: neostigmine and glycopyrrolate or atropine; Drug: Placebo to sugammadex

Interventions

Sugammadex DRUG

Sugammadex 4 mg/kg intravenously

Also known as: SCH 900616, MK-8616

Sugammadex

neostigmine and glycopyrrolate or atropine DRUG

Neostigmine and glycopyrrolate or neostigmine and atropine administered intravenously per usual practice and per the product labels

Usual Care

Placebo to neostigmine DRUG

Normal saline (NaCl 0.9%)

Sugammadex

Placebo to sugammadex DRUG

Normal saline (NaCl 0.9%)

Usual Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 25208233 RESULT

MeSH Terms

Conditions

Thrombosis

Interventions

Sugammadex; Neostigmine; Glycopyrrolate; Atropine

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates; Phenylammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Atropine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2011
• First Posted: August 23, 2011
• Study Start: October 12, 2011
• Primary Completion: September 26, 2012
• Study Completion: September 26, 2012
• Last Updated: February 12, 2021
• Results First Posted: October 30, 2013

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share