- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01422304
Reversal of Neuromuscular Blockade With Sugammadex or Usual Care in Hip Fracture Surgery or Joint (Hip/Knee) Replacement (P07038)
January 20, 2021 updated by: Merck Sharp & Dohme LLC
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)
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.
Study Overview
Status
Completed
Conditions
Detailed Description
Participants will be randomized to sugammadex or usual care in a 1:1 ratio.
Study Type
Interventional
Enrollment (Actual)
1198
Phase
- Phase 3
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
Sugammadex 4 mg/kg intravenously
Other Names:
Normal saline (NaCl 0.9%)
|
Experimental: 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.
|
Neostigmine and glycopyrrolate or neostigmine and atropine administered intravenously per usual practice and per the product labels
Normal saline (NaCl 0.9%)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 24 hours post study drug administration
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change From Baseline in Activated Partial Thromboplastin Time (aPTT) at 10 and 60 Minutes Post Study Drug Administration
Time Frame: Baseline, 10 and 60 minutes post study drug administration
|
Change from baseline in aPTT is identified in study protocol as the Key Secondary Outcome Measure.
Blood samples for determination of aPTT values were obtained at baseline and at 10 and 60 minutes after study drug administration.
aPTT is a performance indicator measuring the efficacy of the intrinsic and common blood coagulation (blood clotting) pathways.
Higher values of aPTT indicate a reduction in the clotting tendency of blood.
|
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
Time Frame: Baseline, 10 and 60 minutes post study drug administration
|
Change from baseline in PT(INR) is identified in study protocol as an Other Secondary Outcome Measure.
Blood samples for determination of PT(INR) values were obtained at baseline and at 10 and 60 minutes after study drug administration.
PT(INR) is a performance indicator measuring the efficacy of the extrinsic and common blood coagulation (blood clotting) pathways.
The INR is the ratio of a participant's prothrombin time to a normal (control) sample, raised to the power of the International Sensitivity Index (ISI) value for the analytical system used (INR = [PT-Test/PT-Normal]^ISI).
Higher values of PT(INR) indicate a reduction in the clotting tendency of blood.
|
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
Time Frame: Up to 14 days post study drug administration
|
This Measure is identified in study protocol as an Other Secondary Outcome Measure.
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 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 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
Time Frame: Up to 24 hours post study drug administration
|
This Measure is identified in study protocol as an Other Secondary Outcome Measure.
All SUAEB were evaluated by a blinded external Adjudication Committee.
Major bleeding event (MBE) = one or more of the following: 1) Fatal bleeding; 2) Bleeding that is symptomatic and occurs in critical area/organ, in a non-operated joint, or is intramuscular with compartment syndrome; 3) Extrasurgical site bleeding causing a fall in hemoglobin (Hgb) level of 20 g/L (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red blood cells (RBCs), occurring within 24 hours of the bleeding; 4) Surgical site bleeding requiring second intervention, or bleeding at operated joint that interferes with rehabilitation; or 5) Surgical site bleeding that is unexpected/prolonged and/or causes hemodynamic instability, with fall in Hgb level of at least 20 g/L (1.24 mmol/L) or transfusion of at least two units of whole blood or RBCs, occurring within 24 hours of the bleeding.
|
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
Time Frame: Up to 14 days post study drug administration
|
This Measure is identified in study protocol as an Other Secondary Outcome Measure.
All SUAEB were evaluated by a blinded external Adjudication Committee.
MBE = one or more of the following: 1) Fatal bleeding; 2) Bleeding that is symptomatic and occurs in critical area/organ, in a non-operated joint, or is intramuscular with compartment syndrome; 3) Extrasurgical site bleeding causing a fall in Hgb level of 20 g/L (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or RBCs, occurring within 24 hours of the bleeding; 4) Surgical site bleeding requiring second intervention, or bleeding at operated joint that interferes with rehabilitation; or 5) Surgical site bleeding that is unexpected/prolonged and/or causes hemodynamic instability, with fall in Hgb level of at least 20 g/L (1.24 mmol/L) or transfusion of at least two units of whole blood or RBCs, occurring within 24 hours of the bleeding.
|
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
Time Frame: Up to 14 days post study drug administration
|
This Measure is identified in study protocol as an Other Secondary Outcome Measure.
Suspected symptomatic VTE events were evaluated by a blinded external Adjudication Committee.
The confirmation of a VTE event was based on determination of a clinically meaningful venous thrombosis (e.g., pulmonary embolism or deep vein thrombosis).
|
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
Time Frame: Up to 14 days post study drug administration
|
This Measure is identified in study protocol as an Other Secondary Outcome Measure.
Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death.
Adverse events suggestive of hypersensitivity which met defined criteria (e.g., serious event) and/or suspected events of anaphylaxis were evaluated by a blinded external Adjudication Committee to determine whether such events met either of the following two criteria for anaphylaxis (Sampson et al.
J Allergy Clin Immunol 2006;117:391-7) - 1. Acute onset of an illness with involvement of the skin, mucosal tissue or both, and at least one of the following: a) respiratory compromise, b) reduced blood pressure (BP) or associated symptoms of end-organ dysfunction.
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that participant: a) involvement of the skin-mucosal tissue, b) respiratory compromise, c) reduced BP or associated symptoms, d) persistent gastrointestinal symptoms.
|
Up to 14 days post study drug administration
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Postoperative Drainage Volume Within 24 Hours After Study Drug Administration
Time Frame: Up to 24 hours post study drug administration
|
The total volume of postoperative drainage from the surgical site over the 24 hours after study drug administration was recorded.
|
Up to 24 hours post study drug administration
|
Number of Participants Requiring Any Postoperative Transfusion
Time Frame: From end of study drug administration through approximately 120 hours after study drug administration
|
The number of participants who received a transfusion unit (e.g., whole blood, packed RBCs, cell saver RBCs, fresh frozen plasma, platelets) that started after study drug administration and within 120 hours after study drug administration (or within 48 hours after any previous [i.e., predose] transfusion for participants who had received a previous transfusion) was determined.
|
From end of study drug administration through approximately 120 hours after study drug administration
|
Total Transfusion Volume in Participants Who Required Postoperative Transfusion
Time Frame: From end of study drug administration through approximately 120 hours after study drug administration
|
Among participants who received a transfusion unit (e.g., whole blood, packed RBCs, cell saver RBCs, fresh frozen plasma, platelets) that started after study drug administration and within 120 hours after study drug administration (or within 48 hours after any previous [i.e., predose] transfusion for participants who had received a previous transfusion), the total volume of blood transfused post study drug was calculated.
The volume of blood transfused post study drug (using linear interpolation when transfusions were ongoing at the time of study drug administration) was converted to grams of Hgb transfused, using RBC concentration information received from the investigators.
The sum of Hgb transfused was standardized to "normal" volume Hgb in homologous whole blood, using 20 g/dL Hgb for calculation of the standardized volume.
|
From end of study drug administration through approximately 120 hours after study drug administration
|
Postoperative Changes in Hgb Concentrations Using the Bleeding Index
Time Frame: Baseline and Visit 3 (24-48 hours post study drug administration)
|
The Bleeding Index was used to describe postoperative changes in Hgb concentrations at Visit 3. Bleeding Index = Hgb level at Visit 3 - Hgb level at baseline, adjusted for the amount of RBCs transfused.
Missing baseline Hgb values were imputed using the overall mean Hgb value at baseline.
|
Baseline and Visit 3 (24-48 hours post study drug administration)
|
Number of Participants With One or More Postoperative Anemia Adverse Events With Onset Within 72 Hours After Study Drug Administration
Time Frame: Up to 72 hours post study drug administration
|
This measure is the incidence of postoperative anaemia with an onset within 72 hours after study drug administration.
A participant is included in the count for this measure if an adverse event with any of the following event terms occurred in the participant with onset within the defined time frame: postoperative anaemia, anaemia, haemorrhagic anaemia, haemoglobin decreased or haemoglobin S decreased.
|
Up to 72 hours post study drug administration
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 12, 2011
Primary Completion (Actual)
September 26, 2012
Study Completion (Actual)
September 26, 2012
Study Registration Dates
First Submitted
August 22, 2011
First Submitted That Met QC Criteria
August 22, 2011
First Posted (Estimate)
August 23, 2011
Study Record Updates
Last Update Posted (Actual)
February 12, 2021
Last Update Submitted That Met QC Criteria
January 20, 2021
Last Verified
January 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Fractures, Bone
- Wounds and Injuries
- Leg Injuries
- Femoral Fractures
- Hip Injuries
- Hip Fractures
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Parasympatholytics
- Autonomic Agents
- Peripheral Nervous System Agents
- Muscarinic Antagonists
- Cholinergic Antagonists
- Cholinergic Agents
- Enzyme Inhibitors
- Adjuvants, Anesthesia
- Bronchodilator Agents
- Anti-Asthmatic Agents
- Respiratory System Agents
- Cholinesterase Inhibitors
- Mydriatics
- Parasympathomimetics
- Glycopyrrolate
- Atropine
- Neostigmine
Other Study ID Numbers
- P07038
- 2011-001201-27 (EudraCT Number)
- MK-8616-059 (Other Identifier: Merck protocol number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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