Efficacy, Safety, and Pharmacokinetics of Sugammadex for Reversal of Neuromuscular Blockade (NMB) in Pediatric Participants (MK-8616-089)
- Conditions
- Neuromuscular Blockade
- Interventions
- Registration Number
- NCT03351608
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This trial will evaluate the efficacy, safety, and pharmacokinetics of sugammadex for the reversal of both moderate and deep neuromuscular blockade (NMB) induced by either rocuronium or vecuronium in pediatric participants. The primary efficacy hypothesis of this investigation is that sugammadex is superior to neostigmine in reversing moderate NMB in pediatric participants as measured by time to recovery to a train-of-four (TOF) ratio of ≥0.9.
- Detailed Description
This trial will be conducted in two parts: Part A and Part B. In Part A, pharmacokinetic (PK) sampling will be conducted to identify the pediatric dose providing sugammadex exposure similar to adults. For Part B participants, the efficacy of sugammadex (i.e. time to recovery of the TOF ratio) will be assessed. Further, safety analyses will be conducted in both Parts A and B. Following completion of Part A, an interim analysis (IA) of the PK and safety data will be performed. Once the appropriate doses are confirmed and safety data is assessed for the 2 doses of sugammadex, then Part B will commence.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 288
- Be categorized as American Society of Anesthesiologists (ASA) Physical Status Class 1, 2, or 3.
- Have a planned non-emergent surgical procedure or clinical situation (e.g., intubation) that requires moderate or deep NMB with either rocuronium or vecuronium.
- Have a planned surgical procedure or clinical situation that would allow objective neuromuscular monitoring techniques to be applied with access to the arm for neuromuscular transmission monitoring.
- Age between 2 to <17 years at Visit 2.
- If female, may participate if she is not pregnant, not breastfeeding, and at least one of the following: 1) Not a woman of childbearing potential (WOCBP); or 2) A WOCBP who agrees to follow the study contraceptive guidance during the treatment period and for at least 7 days after the last dose of study treatment.
- Has any clinically significant condition or situation (eg, anatomical malformation that complicates intubation) other than the condition being studied that, in the opinion of the investigator, would interfere with the trial evaluations or optimal participation in the trial.
- Has a neuromuscular disorder that may affect NMB and/or trial assessments.
- Is dialysis-dependent or has (or is suspected of having) severe renal insufficiency (defined as estimated glomerular filtration rate (eGFR) <30 ml/min).
- Has or is suspected of having a family or personal history of malignant hyperthermia.
- Has or is suspected of having an allergy to study treatments or its/their excipients, to opioids/opiates, muscle relaxants or their excipients, or other medication(s) used during general anesthesia.
- Has received or is planned to receive toremifene and/or fusidic acid via IV administration within 24 hours before or within 24 hours after administration of study treatment.
- Has been previously treated with sugammadex or has participated in a sugammadex clinical trial.
- Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 30 days of signing the informed consent/assent for this current trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sugammadex 4 mg/kg (Part A) Sugammadex 4 mg/kg Single i.v. bolus of sugammadex at 4 mg/kg. Neostigmine (Part B) Neostigmine + Atropine Single i.v. bolus containing neostigmine (50 μg/kg; up to 5 mg maximum dose) in combination with either glycopyrrolate (10 μg/kg) or atropine sulfate (20 μg/kg). Sugammadex 2 mg/kg (Part A) Sugammadex 2 mg/kg Single intravenous (i.v.) bolus of sugammadex at 2 mg/kg. Sugammadex 2 mg/kg (Part B) Sugammadex 2 mg/kg Single i.v. bolus of sugammadex at 2 mg/kg. Sugammadex 4 mg/kg (Part B) Sugammadex 4 mg/kg Single i.v. bolus of sugammadex at 4 mg/kg. Neostigmine (Part B) Neostigmine + Glycopyrrolate Single i.v. bolus containing neostigmine (50 μg/kg; up to 5 mg maximum dose) in combination with either glycopyrrolate (10 μg/kg) or atropine sulfate (20 μg/kg).
- Primary Outcome Measures
Name Time Method Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to Infinity (AUC0-∞) of Sugammadex [Part A] 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose The AUCo-∞ for sugammadex, defined as the area under the plasma concentration versus time plot, was determined in each Part A arm.
Plasma Clearance (CL) of Sugammadex [Part A] 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose The CL of sugammadex, defined as the rate of elimination relative to plasma concentration, was determined in each Part A arm.
Apparent Volume of Distribution (Vz) of Sugammadex [Part A] 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose The Vz of sugammadex, defined as the amount of drug administered relative to plasma concentrations, was determined in each Part A arm.
Maximum Plasma Concentration (Cmax) of Sugammadex [Part A] 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose The Cmax of sugammadex, defined as the maximum plasma concentration, was determined in each Part A arm.
Plasma Half-Life (t½) of Sugammadex [Part A] 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose The t½ of sugammadex, defined as the time required for the plasma concentration to decrease to 50% of maximum, was determined in each Part A arm.
Percentage of Participants With ≥1 Adverse Event (AE) [Parts A and B] Up to 7 days The percentage of participants with ≥1 AE(s) for up to 7 days after treatment was determined for each treatment group, pooled according to treatment received. An AE is defined as any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated.
Time to Recovery of Participant Train-of-Four (TOF) Ratio to ≥0.9 [Part B] Up to 30 minutes post-dose The time to recovery of TOF ratio to ≥0.9 after administration of study intervention was determined for each Part B arm. The TOF ratio is the ratio of the magnitude of the fourth (T4) and first (T1) thumb twitches elicited by 4 electrical stimulations of the ulnar nerve, indicating the current degree of NMB as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Values closer to 1 indicate less NMB. Per protocol, the efficacy analysis is based on comparison of the Part B: Sugammadex 2 mg arm versus the Part B: Neostigmine + (Glycopyrrolate or Atropine) arm.
- Secondary Outcome Measures
Name Time Method Time to Recovery of Participant TOF Ratio to ≥0.7 [Part B] Up to 30 minutes post-dose The time to recovery of TOF ratio to ≥0.7 after administration of study intervention was determined for each Part B arm. The TOF ratio is the ratio of the magnitude of the fourth (T4) and first (T1) thumb twitches elicited by 4 electrical stimulations of the ulnar nerve, indicating the current degree of NMB as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Values closer to 1 indicate less NMB.
Time to Recovery of Participant TOF Ratio to ≥0.8 [Part B] Up to 30 minutes post-dose The time to recovery of TOF ratio to ≥0.8 after administration of study intervention was determined for each Part B arm. The TOF ratio is the ratio of the magnitude of the fourth (T4) and first (T1) thumb twitches elicited by 4 electrical stimulations of the ulnar nerve, indicating the current degree of NMB as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Values closer to 1 indicate less NMB.
Trial Locations
- Locations (30)
West Virginia University ( Site 0043)
🇺🇸Morgantown, West Virginia, United States
Lucille Packard Children's Hospital ( Site 0006)
🇺🇸Palo Alto, California, United States
Children's National Medical Center ( Site 0008)
🇺🇸Washington, District of Columbia, United States
Josephs-Hospitals Warendorf ( Site 0353)
🇩🇪Warendorf, Germany
Childrens Hospital Los Angeles ( Site 0030)
🇺🇸Los Angeles, California, United States
Children's Hospital of Pittsburgh of UPMC ( Site 0005)
🇺🇸Pittsburgh, Pennsylvania, United States
Sozialmedizinisches Zentrum Ost - Donauspital ( Site 0150)
🇦🇹Wien, Austria
Hospital Universitario La Paz ( Site 0502)
🇪🇸Madrid, Spain
Klinikum am Steinenberg Reutlingen ( Site 0351)
🇩🇪Reutlingen, Germany
St. Franziskus-Hospital ( Site 0352)
🇩🇪Muenster, Germany
Saint Peter's University Hospital [New Brunswick, NJ] ( Site 0009)
🇺🇸New Brunswick, New Jersey, United States
The Children's Hospital of Philadelphia ( Site 0015)
🇺🇸Philadelphia, Pennsylvania, United States
Diakovere Annastift gGmbH ( Site 0354)
🇩🇪Hannover, Germany
Uludag Universitesi Tip Fakultesi ( Site 0553)
🇹🇷Bursa, Turkey
Klinikum Rechts der Isar Technische Universitaet Muenchen ( Site 0350)
🇩🇪Muenchen, Germany
Rigshospitalet ( Site 0250)
🇩🇰Copenhagen, Denmark
UZ Leuven Campus Gasthuisberg ( Site 0201)
🇧🇪Leuven, Belgium
Universitaetsklinikum Giessen und Marburg GmbH ( Site 0355)
🇩🇪Marburg, Germany
Hospital Santa Lucia ( Site 0501)
🇪🇸Cartagena, Spain
Clinica Universitaria de Navarra ( Site 0500)
🇪🇸Pamplona, Spain
Koc Universitesi Hastanesi ( Site 0555)
🇹🇷Istanbul, Turkey
Ankara Universitesi Tip Fakultesi ( Site 0551)
🇹🇷Ankara, Turkey
Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0552)
🇹🇷Istanbul, Turkey
Hospital Universitario Nino Jesus ( Site 0503)
🇪🇸Madrid, Spain
Universitaire Ziekenhuis Antwerpen - UZA ( Site 0200)
🇧🇪Edegem, Belgium
New Childrens Hospital ( Site 0750)
🇫🇮Helsinki, Finland
Rady Children's Hospital-San Diego ( Site 0035)
🇺🇸San Diego, California, United States
C.S. Mott Children's Hospital/ University of Michigan Medical center ( Site 0014)
🇺🇸Ann Arbor, Michigan, United States
Memorial Hermann Medical Center University of Texas Medical School ( Site 0038)
🇺🇸Houston, Texas, United States
Duke University Medical Center ( Site 0019)
🇺🇸Durham, North Carolina, United States