Back to resultsDialysis of Sugammadex in Participants With Severe Renal Impairment (Study 19.4.333) (P05773)
Primary Purpose
Neuromuscular Blockade
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
sugammadex
Rocuronium
Sponsored by
About this trial
This is an interventional treatment trial for Neuromuscular Blockade
Eligibility Criteria
Inclusion Criteria:
- At least 18 years of age
- American Society of Anesthesiologists (ASA) Class >=4
- Creatinine clearance (CLCR) < 30 mL/min and clinical indication for dialysis
- Hospitalization at Intensive Care Unit (ICU) and scheduled for a (surgical) procedure under general anesthesia requiring neuromuscular relaxation with the use of rocuronium
- Scheduled for a (surgical) procedure in supine position
- Written informed consent (of the legal representative)
Exclusion Criteria:
- Known or suspected to have neuromuscular disorders impairing neuromuscular blockade and/or significant hepatic dysfunction
- Known or suspected to have a (family) history of malignant hyperthermia
- Known or suspected to have an allergy to narcotics, muscle relaxants or other medication used during general anesthesia
- Have already participated in a sugammadex trial
- Have participated in another clinical trial, not preapproved by NV Organon, within 30 days of study entry
- Females who are pregnant*
- Females who are breast-feeding * In females pregnancy will be excluded both from medical history and by a human chorionic gonadotropin (hCG) test within 24 hours before surgery except in females who are not of childbearing potential, i.e. at least 2 years menopausal or have undergone tubal ligation or an hysterectomy.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Sugammadex
Arm Description
IV single bolus dose of 4.0 mg/kg sugammadex
Outcomes
Primary Outcome Measures
Clearance of Sugammadex by Dialysis as Measured by the Reduction Ratio (RR)
Starting on Day 1 dialysis was performed on four separate occasions using a Fresenius 40008H hemodialyzer, with a hemodiafilter standard helixone membrane FX 600. Dialysate samples were collected before, and after hemodialysis, with concentrations of sugammadex determined using a liquid chromatographic assay with mass spectrometric detection. The clearance of sugammadex at each dialysis session was calculated by measuring the ratio of plasma concentration at the end of dialysis, average duration of 6 hours, compared with that immediately before the start of dialysis, called the RR.
Clearance of Rocuronium by Dialysis as Measured by the Reduction Ratio (RR)
Starting on Day 1 dialysis was performed on four separate occasions using a Fresenius 40008H hemodialyzer, with a hemodiafilter standard helixone membrane FX 600. Dialysate samples were collected before, and after hemodialysis, with concentrations of rocuronium determined using a liquid chromatographic assay with mass spectrometric detection. The clearance of rocuronium at each dialysis session was calculated by measuring the ratio of plasma concentration at the end of dialysis, average duration of 6 hours, compared with that immediately before the start of dialysis, called the RR.
Rate of Clearance of Sugammadex From Blood
Starting on Day 1 dialysis was performed on four separate occasions using a Fresenius 40008H hemodialyzer, with a hemodiafilter standard helixone membrane FX 600. Blood samples were collected from ports in the arterial and venous tubing of the dialyzer before, during and after an average of 6 hours of hemodialysis. The concentrations of sugammadex were determined using a liquid chromatographic assay with mass spectrometric detection. The clearance rate from blood at each dialysis session was assessed by averaging across all available collection time points.
Rate of Clearance of Rocuronium From Blood
Starting on Day 1 dialysis was performed on four separate occasions using a Fresenius 40008H hemodialyzer, with a hemodiafilter standard helixone membrane FX 600. Blood samples were collected from ports in the arterial and venous tubing of the dialyzer before, during and after an average of 6 hours of hemodialysis. The concentrations of rocuronium were determined using a liquid chromatographic assay with mass spectrometric detection. The clearance rate from blood at each dialysis session was assessed by averaging across all available collection time points.
Rate of Clearance of Sugammadex From Dialysate
Starting on Day 1 dialysis was performed on four separate occasions using a Fresenius 40008H hemodialyzer, with a hemodiafilter standard helixone membrane FX 600. Dialysate samples were collected from a port in the outflow of the dialyzer before, during and after an average of 6 hours of hemodialysis. The concentrations of sugammadex were determined using a liquid chromatographic assay with mass spectrometric detection. The clearance rate from dialysate at each dialysis session was assessed by averaging across all available collection time points.The data from the fourth dialysis are not presented as they were not calculable.
Rate of Clearance of Rocuronium From Dialysate
Starting on Day 1 dialysis was performed on four separate occasions using a Fresenius 40008H hemodialyzer, with a hemodiafilter standard helixone membrane FX 600. Dialysate samples were collected from a port in the outflow of the dialyzer before, during and after an average of 6 hours of hemodialysis. The concentrations of rocuronium were determined using a liquid chromatographic assay with mass spectrometric detection. The clearance rate from dialysate at each dialysis session was assessed by averaging across all available collection time points.
Secondary Outcome Measures
Number of Participants With Pre-treatment Adverse Events (AEs)
An AE is any unfavorable and unintended change in the structure, function or chemistry of the body, whether or not related to the use of a product.
Number of Participants With Serious Adverse Events (SAEs)
A SAE is any untoward medical occurrence that at any dose results in the following: death, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or is a congenital anomaly/birth defect
Number of Participants With Medical Device (Near) Incidents
A medical device (near) incident is defined as an occurrence due to inaccurate or inadequate labeling/instructions, or information supplied with a medical device; or malfunction, deterioration or recall of a medical device that could lead to death or serious deterioration in health.
Vital Sign: Mean Systolic Blood Pressure
Systolic blood pressure was measured at the following time points: screening, before rocuronium treatment, before sugammadex treatment, at 2, 5, 10, 20 minutes post-sugammadex treatment, and the day after surgery
Vital Sign: Mean Diastolic Blood Pressure
Diastolic blood pressure was measured at the following time points: screening, before rocuronium treatment, before sugammadex treatment, at 2, 5, 10, 20 minutes post-sugammadex treatment, and the day after surgery
Vital Sign: Mean Heart Rate
Heart rate was measured at the following time points: screening, before rocuronium treatment, before sugammadex treatment, at 2, 5, 10, 20 minutes post-sugammadex treatment, and the day after surgery
Number of Participants With Physical Examinations
Physical examinations were to be conducted at screening, on Day 1 and 7 days after surgery
Number of Participants With Reoccurrence of Neuromuscular Blockade at Day 1
Neuromuscular function was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing the magnitudes (heights) of the first twitch (T1) and fourth twitch (T4) response at the adductor pollicis muscle with a TOF-Watch® SX. Stimulation continued until the T4/T1 ratio reached at least 0.9. Higher T4/T1 ratios represent greater recovery from neuromuscular blockade; with a value of 1.0 representing full recovery. Reoccurrence of neuromuscular blockade is defined as a decline in the T4/T1 ratio from >= 0.9 to < 0.8 in at least three consecutive measurements.
Number of Participants With Events Due to Possible Interaction of Sugammadex With Endo-/Exogenous Compounds Other Than Rocuronium
Evidence of AEs due to possible interaction of sugammadex with endogenous compounds or with exogenous compounds other than rocuronium
Number of Participants With Pregnancies at 30 Days Post-dose
Pregnancies reported by means of a Pregnancy Reporting Form, consist of pregnant female participants or pregnant female partners of male participants
Time From Start of Administration of Sugammadex to Recovery of T4/T1 Ratio to 0.9
Neuromuscular function was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing the magnitudes (heights) of the first twitch (T1) and fourth twitch (T4) response at the adductor pollicis muscle with a TOF-Watch® SX. Stimulation continued until the T4/T1 ratio reached at least 0.9. Higher T4/T1 ratios represent greater recovery from neuromuscular blockade; with a value of 1.0 representing full recovery.
Time From Start of Administration of Sugammadex to Recovery of T4/T1 Ratio to 0.8
Neuromuscular function was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds and assessing the magnitudes (heights) of the T1 and T4 response at the adductor pollicis muscle with a TOF-Watch® SX. Stimulation continued until the T4/T1 ratio reached at least 0.8. Higher T4/T1 ratios represent greater recovery from neuromuscular blockade; with a value of 1.0 representing full recovery.
Time From Start of Administration of Sugammadex to Recovery of T4/T1 Ratio to 0.7
Neuromuscular function was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds and assessing the magnitudes (heights) of the T1 and T4 response at the adductor pollicis muscle with a TOF-Watch® SX. Stimulation continued until the T4/T1 ratio reached at least 0.7. Higher T4/T1 ratios represent greater recovery from neuromuscular blockade; with a value of 1.0 representing full recovery.
Full Information
NCT ID
NCT00656799
First Posted
April 7, 2008
Last Updated
February 20, 2015
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT00656799
Brief Title
Dialysis of Sugammadex in Participants With Severe Renal Impairment (Study 19.4.333) (P05773)
Official Title
A Single Center, Open-Label Trial in Subjects With Severe Renal Impairment Evaluating the Dialysability of the Sugammadex-Rocuronium Complex
Study Type
Interventional
2. Study Status
Record Verification Date
February 2015
Overall Recruitment Status
Completed
Study Start Date
April 2008 (undefined)
Primary Completion Date
July 2009 (Actual)
Study Completion Date
July 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The clinical trial objectives were to evaluate the dialysability of the sugammadex-rocuronium complex; it's safety and efficacy in participants with severe renal impairment.
Detailed Description
The current trial was designed to evaluate the dialysability of the sugammadex-rocuronium complex in participants with severe renal impairment. A dose of 4.0 mg/kg sugammadex was administered 15 minutes after administration of 0.6 mg/kg rocuronium. Blood and dialysate samples were collected before, during and after hemodialysis/filtration, for calculation of clearance of sugammadex-rocuronium complex and assessment of rebound.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuromuscular Blockade
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sugammadex
Arm Type
Experimental
Arm Description
IV single bolus dose of 4.0 mg/kg sugammadex
Intervention Type
Drug
Intervention Name(s)
sugammadex
Other Intervention Name(s)
Org 25969, SCH 900616, MK-8616, Bridion®
Intervention Description
At 15 minutes after administration of rocuronium, an IV single bolus dose of 4.0 mg/kg sugammadex was administered.
Intervention Type
Drug
Intervention Name(s)
Rocuronium
Other Intervention Name(s)
Rocuronium bromide, Esmeron®
Intervention Description
After achieving stable anesthesia an IV single bolus dose of 0.6 mg/kg rocuronium was administered
Primary Outcome Measure Information:
Title
Clearance of Sugammadex by Dialysis as Measured by the Reduction Ratio (RR)
Description
Starting on Day 1 dialysis was performed on four separate occasions using a Fresenius 40008H hemodialyzer, with a hemodiafilter standard helixone membrane FX 600. Dialysate samples were collected before, and after hemodialysis, with concentrations of sugammadex determined using a liquid chromatographic assay with mass spectrometric detection. The clearance of sugammadex at each dialysis session was calculated by measuring the ratio of plasma concentration at the end of dialysis, average duration of 6 hours, compared with that immediately before the start of dialysis, called the RR.
Time Frame
Up to day 7
Title
Clearance of Rocuronium by Dialysis as Measured by the Reduction Ratio (RR)
Description
Starting on Day 1 dialysis was performed on four separate occasions using a Fresenius 40008H hemodialyzer, with a hemodiafilter standard helixone membrane FX 600. Dialysate samples were collected before, and after hemodialysis, with concentrations of rocuronium determined using a liquid chromatographic assay with mass spectrometric detection. The clearance of rocuronium at each dialysis session was calculated by measuring the ratio of plasma concentration at the end of dialysis, average duration of 6 hours, compared with that immediately before the start of dialysis, called the RR.
Time Frame
Up to Day 7
Title
Rate of Clearance of Sugammadex From Blood
Description
Starting on Day 1 dialysis was performed on four separate occasions using a Fresenius 40008H hemodialyzer, with a hemodiafilter standard helixone membrane FX 600. Blood samples were collected from ports in the arterial and venous tubing of the dialyzer before, during and after an average of 6 hours of hemodialysis. The concentrations of sugammadex were determined using a liquid chromatographic assay with mass spectrometric detection. The clearance rate from blood at each dialysis session was assessed by averaging across all available collection time points.
Time Frame
Up to day 7
Title
Rate of Clearance of Rocuronium From Blood
Description
Starting on Day 1 dialysis was performed on four separate occasions using a Fresenius 40008H hemodialyzer, with a hemodiafilter standard helixone membrane FX 600. Blood samples were collected from ports in the arterial and venous tubing of the dialyzer before, during and after an average of 6 hours of hemodialysis. The concentrations of rocuronium were determined using a liquid chromatographic assay with mass spectrometric detection. The clearance rate from blood at each dialysis session was assessed by averaging across all available collection time points.
Time Frame
Up to Day 7
Title
Rate of Clearance of Sugammadex From Dialysate
Description
Starting on Day 1 dialysis was performed on four separate occasions using a Fresenius 40008H hemodialyzer, with a hemodiafilter standard helixone membrane FX 600. Dialysate samples were collected from a port in the outflow of the dialyzer before, during and after an average of 6 hours of hemodialysis. The concentrations of sugammadex were determined using a liquid chromatographic assay with mass spectrometric detection. The clearance rate from dialysate at each dialysis session was assessed by averaging across all available collection time points.The data from the fourth dialysis are not presented as they were not calculable.
Time Frame
Up to day 7
Title
Rate of Clearance of Rocuronium From Dialysate
Description
Starting on Day 1 dialysis was performed on four separate occasions using a Fresenius 40008H hemodialyzer, with a hemodiafilter standard helixone membrane FX 600. Dialysate samples were collected from a port in the outflow of the dialyzer before, during and after an average of 6 hours of hemodialysis. The concentrations of rocuronium were determined using a liquid chromatographic assay with mass spectrometric detection. The clearance rate from dialysate at each dialysis session was assessed by averaging across all available collection time points.
Time Frame
Up to Day 7
Secondary Outcome Measure Information:
Title
Number of Participants With Pre-treatment Adverse Events (AEs)
Description
An AE is any unfavorable and unintended change in the structure, function or chemistry of the body, whether or not related to the use of a product.
Time Frame
Screening up to Day 1
Title
Number of Participants With Serious Adverse Events (SAEs)
Description
A SAE is any untoward medical occurrence that at any dose results in the following: death, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or is a congenital anomaly/birth defect
Time Frame
Up to day 7
Title
Number of Participants With Medical Device (Near) Incidents
Description
A medical device (near) incident is defined as an occurrence due to inaccurate or inadequate labeling/instructions, or information supplied with a medical device; or malfunction, deterioration or recall of a medical device that could lead to death or serious deterioration in health.
Time Frame
Up to day 7
Title
Vital Sign: Mean Systolic Blood Pressure
Description
Systolic blood pressure was measured at the following time points: screening, before rocuronium treatment, before sugammadex treatment, at 2, 5, 10, 20 minutes post-sugammadex treatment, and the day after surgery
Time Frame
Screening up to 1 day after surgery
Title
Vital Sign: Mean Diastolic Blood Pressure
Description
Diastolic blood pressure was measured at the following time points: screening, before rocuronium treatment, before sugammadex treatment, at 2, 5, 10, 20 minutes post-sugammadex treatment, and the day after surgery
Time Frame
Screening up to 1 day after surgery
Title
Vital Sign: Mean Heart Rate
Description
Heart rate was measured at the following time points: screening, before rocuronium treatment, before sugammadex treatment, at 2, 5, 10, 20 minutes post-sugammadex treatment, and the day after surgery
Time Frame
Screening up to 1 day after surgery
Title
Number of Participants With Physical Examinations
Description
Physical examinations were to be conducted at screening, on Day 1 and 7 days after surgery
Time Frame
Screening up to day 7
Title
Number of Participants With Reoccurrence of Neuromuscular Blockade at Day 1
Description
Neuromuscular function was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing the magnitudes (heights) of the first twitch (T1) and fourth twitch (T4) response at the adductor pollicis muscle with a TOF-Watch® SX. Stimulation continued until the T4/T1 ratio reached at least 0.9. Higher T4/T1 ratios represent greater recovery from neuromuscular blockade; with a value of 1.0 representing full recovery. Reoccurrence of neuromuscular blockade is defined as a decline in the T4/T1 ratio from >= 0.9 to < 0.8 in at least three consecutive measurements.
Time Frame
Day 1
Title
Number of Participants With Events Due to Possible Interaction of Sugammadex With Endo-/Exogenous Compounds Other Than Rocuronium
Description
Evidence of AEs due to possible interaction of sugammadex with endogenous compounds or with exogenous compounds other than rocuronium
Time Frame
Day 1
Title
Number of Participants With Pregnancies at 30 Days Post-dose
Description
Pregnancies reported by means of a Pregnancy Reporting Form, consist of pregnant female participants or pregnant female partners of male participants
Time Frame
Up to 30 days post -dose
Title
Time From Start of Administration of Sugammadex to Recovery of T4/T1 Ratio to 0.9
Description
Neuromuscular function was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing the magnitudes (heights) of the first twitch (T1) and fourth twitch (T4) response at the adductor pollicis muscle with a TOF-Watch® SX. Stimulation continued until the T4/T1 ratio reached at least 0.9. Higher T4/T1 ratios represent greater recovery from neuromuscular blockade; with a value of 1.0 representing full recovery.
Time Frame
Day 1
Title
Time From Start of Administration of Sugammadex to Recovery of T4/T1 Ratio to 0.8
Description
Neuromuscular function was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds and assessing the magnitudes (heights) of the T1 and T4 response at the adductor pollicis muscle with a TOF-Watch® SX. Stimulation continued until the T4/T1 ratio reached at least 0.8. Higher T4/T1 ratios represent greater recovery from neuromuscular blockade; with a value of 1.0 representing full recovery.
Time Frame
Day 1
Title
Time From Start of Administration of Sugammadex to Recovery of T4/T1 Ratio to 0.7
Description
Neuromuscular function was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds and assessing the magnitudes (heights) of the T1 and T4 response at the adductor pollicis muscle with a TOF-Watch® SX. Stimulation continued until the T4/T1 ratio reached at least 0.7. Higher T4/T1 ratios represent greater recovery from neuromuscular blockade; with a value of 1.0 representing full recovery.
Time Frame
Day 1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
At least 18 years of age
American Society of Anesthesiologists (ASA) Class >=4
Creatinine clearance (CLCR) < 30 mL/min and clinical indication for dialysis
Hospitalization at Intensive Care Unit (ICU) and scheduled for a (surgical) procedure under general anesthesia requiring neuromuscular relaxation with the use of rocuronium
Scheduled for a (surgical) procedure in supine position
Written informed consent (of the legal representative)
Exclusion Criteria:
Known or suspected to have neuromuscular disorders impairing neuromuscular blockade and/or significant hepatic dysfunction
Known or suspected to have a (family) history of malignant hyperthermia
Known or suspected to have an allergy to narcotics, muscle relaxants or other medication used during general anesthesia
Have already participated in a sugammadex trial
Have participated in another clinical trial, not preapproved by NV Organon, within 30 days of study entry
Females who are pregnant*
Females who are breast-feeding * In females pregnancy will be excluded both from medical history and by a human chorionic gonadotropin (hCG) test within 24 hours before surgery except in females who are not of childbearing potential, i.e. at least 2 years menopausal or have undergone tubal ligation or an hysterectomy.
12. IPD Sharing Statement
Citations:
PubMed Identifier
22732111
Citation
Cammu G, Van Vlem B, van den Heuvel M, Stet L, el Galta R, Eloot S, Demeyer I. Dialysability of sugammadex and its complex with rocuronium in intensive care patients with severe renal impairment. Br J Anaesth. 2012 Sep;109(3):382-90. doi: 10.1093/bja/aes207. Epub 2012 Jun 24.
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Dialysis of Sugammadex in Participants With Severe Renal Impairment (Study 19.4.333) (P05773)
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