Dialysis of Sugammadex in Participants With Severe Renal Impairment (Study 19.4.333) (P05773)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00656799
First received: April 7, 2008
Last updated: July 29, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Neuromuscular Blockade
Drug: sugammadex
Drug: Rocuronium
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single Center, Open-Label Trial in Subjects With Severe Renal Impairment Evaluating the Dialysability of the Sugammadex-Rocuronium Complex

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Clearance of Sugammadex by Dialysis as Measured by the Reduction Ratio (RR) [ Time Frame: Up to day 7 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to Day 7 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to day 7 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to Day 7 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to day 7 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to Day 7 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Screening up to Day 1 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Up to day 7 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Up to day 7 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Screening up to 1 day after surgery ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Screening up to 1 day after surgery ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Screening up to 1 day after surgery ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Screening up to day 7 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Up to 30 days post -dose ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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.


Enrollment: 6
Study Start Date: April 2008
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sugammadex
IV single bolus dose of 4.0 mg/kg sugammadex
Drug: sugammadex
At 15 minutes after administration of rocuronium, an IV single bolus dose of 4.0 mg/kg sugammadex was administered.
Other Names:
  • Org 25969
  • SCH 900616
  • MK-8616
  • Bridion®
Drug: Rocuronium
After achieving stable anesthesia an IV single bolus dose of 0.6 mg/kg rocuronium was administered
Other Names:
  • Rocuronium bromide
  • Esmeron®

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00656799     History of Changes
Other Study ID Numbers: P05773, 2007-006934-33
Study First Received: April 7, 2008
Results First Received: May 21, 2013
Last Updated: July 29, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Rocuronium
Neuromuscular Agents
Neuromuscular Blocking Agents
Neuromuscular Nondepolarizing Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014