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Comparison of 4.0 mg/kg Sugammadex at 1-2 Post Tetanic Counts (PTC) in Renal or Control Patients (19.4.328)(P05769AM1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00702715
First received: June 19, 2008
Last updated: October 31, 2014
Last verified: October 2014
  Purpose

The current trial was designed to investigate the effects of 4.0 mg.kg-1 of sugammadex on efficacy, safety and pharmacokinetics in subjects with severe renal impairment in comparison to subjects with normal renal function.


Condition Intervention Phase
Anesthesia
Drug: sugammadex
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-center, Parallel-group, Comparative Trial Evaluating the Efficacy, Pharmacokinetics and Safety of 4.0 mg/kg Sugammadex Administered at 1-2 PTC in Subjects With Normal or Severely Impaired Renal Function

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

Primary Outcome Measures:
  • Time to Recovery of the T4/T1 Ratio to 0.9. [ Time Frame: start of administration of sugammadex to recovery from neuromuscular blockade ] [ Designated as safety issue: No ]
    Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery.


Secondary Outcome Measures:
  • Time to Recovery of the T4/T1 Ratio to 0.8 [ Time Frame: start of administration of sugammadex to recovery from neuromuscular blockade ] [ Designated as safety issue: No ]
    Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery.

  • Time to Recovery of T4/T1 Ratio to 0.7 [ Time Frame: start of administration of sugammadex to recovery from neuromuscular blockade ] [ Designated as safety issue: No ]
    Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery.


Enrollment: 69
Study Start Date: August 2008
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Participants with severe renal impairment
Participants with severe renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Severe renal impairment was defined as creatinine clearance <30mL/min.
Drug: sugammadex

Each subject will receive an

intravenous (i.v.) single bolus dose of 0.6 mg.kg-1 rocuronium. After

this dose, maintenance doses of 0.1 - 0.2 mg.kg-1

rocuronium may be given. In case of maintenance dosing, the target depth of

neuromuscular blockade has to be maintained at 1-2 post-tetanic counts (PTC). After the last dose of rocuronium has been administered, the subject will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC.

Other Name: Org 25959
Active Comparator: Participants with normal renal function
Participants with normal renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Normal renal function was defined as creatinine clearance >=80mL/min.
Drug: sugammadex

Each subject will receive an

intravenous (i.v.) single bolus dose of 0.6 mg.kg-1 rocuronium. After

this dose, maintenance doses of 0.1 - 0.2 mg.kg-1

rocuronium may be given. In case of maintenance dosing, the target depth of

neuromuscular blockade has to be maintained at 1-2 post-tetanic counts (PTC). After the last dose of rocuronium has been administered, the subject will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC.

Other Name: Org 25959

Detailed Description:

The results of previous trials showed that the safety profile of sugammadex

observed in subjects with impaired renal function are not appreciably different from subjects with normal renal function. Reoccurrence of neuromuscular blockade was not observed, and sugammadex was safe and generally well tolerated in subjects with severe renal impairment. In a previous trial, subjects (n=15) with severe renal impairment received a dose of 2.0 mg.kg-1 of sugammadex. The effects of the other proposed recommended dose for routine reversal, 4.0 mg.kg-1, on efficacy, safety and pharmacokinetics had not been studied thus far in subjects with severe renal impairment. The objectives of this trial were to assess equivalence with respect to the efficacy of sugammadex in subjects with normal renal function or severe renal impairment, to evaluate the safety of sugammadex in these subject groups and to compare the pharmacokinetic profiles.

  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
  • ASA class 1-3
  • Creatinine clearance (CLcr) < 30 mL/min and no anticipated clinical

indication for high flux hemodialysis during first 24 hours after

sugammadex administration (for renally impaired group) or CLcr >= 80

mL/min (for control group)

-Scheduled for a surgical procedure under general anesthesia with propofol

requiring neuromuscular relaxation with the use of rocuronium

  • Scheduled for a surgical procedure in supine position
  • Written informed consent

Exclusion Criteria:

- Subjects known or suspected to have neuromuscular disorders impairing

neuromuscular blockade and/or significant hepatic dysfunction

  • Subjects scheduled for renal transplant surgery
  • Subjects known or suspected to have a (family) history of malignant

hyperthermia

-Subjects known or suspected to have an allergy to narcotics, muscle

relaxants or other medication used during general anesthesia

  • Subjects receiving fusidic acid, toremifene and/or flucloxacillin
  • Subjects who have already participated in a sugammadex trial
  • Subjects who have participated in another clinical trial, not pre-approved

by the sponsor, within 30 days of entering into 19.4.328 (P05769)

  • Female subjects who are pregnant
  • Female subjects who are breast-feeding
  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

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00702715     History of Changes
Other Study ID Numbers: P05769, 19.4.328
Study First Received: June 19, 2008
Results First Received: March 15, 2011
Last Updated: October 31, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

ClinicalTrials.gov processed this record on November 20, 2014