Clinical trial NCT03351608: Efficacy, Safety, and Pharmacokinetics of Sugammadex for Reversal of Neuromuscular Blockade (NMB) in Pediatric Participants (MK-8616-089)
Official title: A Phase 4 Double-Blinded, Randomized, Active Comparator-Controlled Clinical Trial to Study the Efficacy, Safety, and Pharmacokinetics of Sugammadex (MK-8616) for Reversal of Neuromuscular Blockade in Pediatric Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Neuromuscular Blockade
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-11-24
Enrollment: 288
Sex: ALL
Minimum age (years): 2
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to Infinity (AUC0-∞) of Sugammadex [Part A]
timeFrame: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
measure: Plasma Clearance (CL) of Sugammadex [Part A]
timeFrame: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
measure: Apparent Volume of Distribution (Vz) of Sugammadex [Part A]
timeFrame: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
measure: Maximum Plasma Concentration (Cmax) of Sugammadex [Part A]
timeFrame: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
measure: Plasma Half-Life (t½) of Sugammadex [Part A]
timeFrame: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
measure: Percentage of Participants With ≥1 Adverse Event (AE) [Parts A and B]
timeFrame: Up to 7 days
measure: Time to Recovery of Participant Train-of-Four (TOF) Ratio to ≥0.9 [Part B]
timeFrame: Up to 30 minutes post-dose
Secondary outcomes:
measure: Time to Recovery of Participant TOF Ratio to ≥0.7 [Part B]
timeFrame: Up to 30 minutes post-dose
measure: Time to Recovery of Participant TOF Ratio to ≥0.8 [Part B]
timeFrame: Up to 30 minutes post-dose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Childrens Hospital Los Angeles ( Site 0030)
state: California
city: Palo Alto
country: United States
facility: Lucille Packard Children's Hospital ( Site 0006)
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital-San Diego ( Site 0035)
state: California
city: Washington
country: United States
facility: Children's National Medical Center ( Site 0008)
state: District of Columbia
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital/ University of Michigan Medical center ( Site 0014)
state: Michigan
city: New Brunswick
country: United States
facility: Saint Peter's University Hospital [New Brunswick, NJ] ( Site 0009)
state: New Jersey
city: Durham
country: United States
facility: Duke University Medical Center ( Site 0019)
state: North Carolina
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia ( Site 0015)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC ( Site 0005)
state: Pennsylvania
city: Houston
country: United States
facility: Memorial Hermann Medical Center University of Texas Medical School ( Site 0038)
state: Texas
city: Morgantown
country: United States
facility: West Virginia University ( Site 0043)
state: West Virginia
city: Wien
country: Austria
facility: Sozialmedizinisches Zentrum Ost - Donauspital ( Site 0150)
city: Edegem
country: Belgium
facility: Universitaire Ziekenhuis Antwerpen - UZA ( Site 0200)
city: Leuven
country: Belgium
facility: UZ Leuven Campus Gasthuisberg ( Site 0201)
city: Copenhagen
country: Denmark
facility: Rigshospitalet ( Site 0250)
city: Helsinki
country: Finland
facility: New Childrens Hospital ( Site 0750)
city: Hannover
country: Germany
facility: Diakovere Annastift gGmbH ( Site 0354)
city: Marburg
country: Germany
facility: Universitaetsklinikum Giessen und Marburg GmbH ( Site 0355)
city: Muenchen
country: Germany
facility: Klinikum Rechts der Isar Technische Universitaet Muenchen ( Site 0350)
city: Muenster
country: Germany
facility: St. Franziskus-Hospital ( Site 0352)
city: Reutlingen
country: Germany
facility: Klinikum am Steinenberg Reutlingen ( Site 0351)
city: Warendorf
country: Germany
facility: Josephs-Hospitals Warendorf ( Site 0353)
city: Cartagena
country: Spain
facility: Hospital Santa Lucia ( Site 0501)
city: Madrid
country: Spain
facility: Hospital Universitario Nino Jesus ( Site 0503)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz ( Site 0502)
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra ( Site 0500)
city: Ankara
country: Turkey
facility: Ankara Universitesi Tip Fakultesi ( Site 0551)
city: Bursa
country: Turkey
facility: Uludag Universitesi Tip Fakultesi ( Site 0553)
city: Istanbul
country: Turkey
facility: Koc Universitesi Hastanesi ( Site 0555)
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0552)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Voss T, Wang A, DeAngelis M, Speek M, Saldien V, Hammer GB, Wrishko R, Herring WJ. Sugammadex for reversal of neuromuscular blockade in pediatric patients: Results from a phase IV randomized study. Paediatr Anaesth. 2022 Mar;32(3):436-445. doi: 10.1111/pan.14370. Epub 2021 Dec 17.