Efficacy, Safety, and Pharmacokinetics of Sugammadex (MK-8616) for Reversal of Neuromuscular Blockade in Pediatric Participants Aged Birth to <2 Years (MK-8616-169)

Neuromuscular Blockade Clinical Trial

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 Aged Birth to <2 Years

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03909165
• Other study ID #: 8616-169
• Secondary ID: MK-8616-1692017-
• Status: Completed
• Phase: Phase 4
• Start date: July 23, 2019
• Est. completion date: September 21, 2023

Study information

• Verified date: September 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy, safety, and pharmacokinetics (PK) of sugammadex (MK-8616) for reversal of both moderate and deep neuromuscular blockade (NMB) in pediatric participants aged birth to <2 years. The primary hypothesis of this study is that sugammadex is superior to neostigmine in reversing moderate NMB as measured by time to neuromuscular recovery.

Description:

This trial will be conducted in two parts: Part A and Part B. In Part A, PK sampling will be conducted to identify the pediatric dose providing sugammadex exposure comparable to the next oldest age cohort. For Part B participants, the efficacy of sugammadex (i.e. neuromuscular recovery / time to extubation) 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 information / eligibility

• Status: Completed
• Enrollment: 137
• Est. completion date: September 21, 2023
• Est. primary completion date: September 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 2 Years

Eligibility

Inclusion Criteria:

• Categorized as American Society of Anesthesiologists (ASA) Physical Status Class 1, 2, or 3.

• Has a planned non-emergent surgical procedure or clinical situation (e.g., intubation) that requires moderate or deep NMB with either rocuronium or vecuronium.

• Has a surgical procedure or clinical situation that would allow neuromuscular monitoring techniques to be applied for neuromuscular transmission monitoring.

• Is male or female, between birth and <2 years of age.

Exclusion Criteria:

• Is a preterm infant or neonate <36 weeks gestational age at birth.

• Has any clinically significant condition or situation (e.g., anatomical malformation that complicates intubation) other than the condition requiring the use of NMBA 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.

• 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.

• Is expected to require mechanical ventilation after the procedure.

• 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.

• Use of medication expected to interfere with study treatments given in this trial.

• Has been previously treated with sugammadex or has participated in a sugammadex clinical trial within 30 days of signing the informed consent form of this current 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.

Related Conditions & MeSH terms

• Neuromuscular Blockade

Intervention

Drug:
• Sugammadex 2 mg/kg
For moderate NMB reversal, a single IV bolus of sugammadex (2 mg/kg) will be given after final dose of neuromuscular blocking agent (NMBA; rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to train-of-four (TOF) stimulations.
• Sugammadex 4 mg/kg
For deep NMB reversal, a single IV bolus of sugammadex (4 mg/kg) will be given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of detection of a target of 1 to 2 post-tetanic counts and no response to TOF stimulations (TOF=0).
• Neostigmine + Glycopyrrolate
For moderate NMB reversal, a single i.v. bolus containing both neostigmine (50 µg/kg; up to 5 mg maximum dose) as well as glycopyrrolate (10 µg/kg) will be given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of the reappearance of T2 in response to TOF stimulations.
• Neostigmine + Atropine
For moderate NMB reversal, a single i.v. bolus containing both neostigmine (50 µg/kg; up to 5 mg maximum dose) as well as atropine (20 µg/kg) will be given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of the reappearance of T2 in response to TOF stimulations.

Locations

Country	Name	City	State
Australia	Royal Childrens Hospital Melbourne ( Site 3801)	Parkville	Victoria
Australia	Queensland Children s Hospital ( Site 3806)	South Brisbane	Queensland
Australia	The Children s Hospital at Westmead ( Site 3805)	Westmead	New South Wales
Belgium	UZ Brussel ( Site 3201)	Brussels	Bruxelles-Capitale, Region De
Belgium	Universitaire Ziekenhuis Antwerpen - UZA ( Site 3200)	Edegem	Antwerpen
Belgium	UZ Leuven - Campus Gasthuisberg ( Site 3202)	Leuven	Vlaams-Brabant
Brazil	Hospital Tacchini ( Site 3827)	Bento Goncalves	Rio Grande Do Sul
Brazil	Hospital Pequeno Principe ( Site 3826)	Curitiba	Parana
Brazil	Instituto da Crianca do Hospital das Clinicas-FMUSP ( Site 3825)	Sao Paulo
Denmark	Rigshospitalet ( Site 3250)	Copenhagen	Hovedstaden
Finland	New Childrens Hospital ( Site 3750)	Helsinki	Uusimaa
France	C.H.R.U. de Lille. Hopital Jeanne de Flandres ( Site 3304)	Lille	Nord
Guatemala	Unidad de Cirugía Cardiovascular ( Site 4126)	Guatemala
Hungary	Debreceni Egyetem Klinikai Kozpont ( Site 4200)	Debrecen
Hungary	Szegedi Tudomanyegyetem ( Site 4201)	Szeged	Csongrad
Malaysia	University Malaya Medical Centre. ( Site 3876)	Kuala Lumpur
Malaysia	Women and Children Hospital Kuala Lumpur (Hospital Tunku Azizah) ( Site 3875)	Kuala Lumpur
Malaysia	Sarawak General Hospital ( Site 3877)	Kuching	Sarawak
Mexico	Centenario Hospital Miguel Hidalgo-Pediatrics Department ( Site 4152)	Aguascalientes
Mexico	Hospital General de Zona No. 1 ( Site 4153)	Villa De Alvarez	Colima
Netherlands	University Medical Center Groningen ( Site 4227)	Groningen
Netherlands	Radboud University Medical Center ( Site 4226)	Nijmegen	Gelderland
Netherlands	Erasmus University Medical Center ( Site 4225)	Rotterdam	Zuid-Holland
Netherlands	Wilhelmina Kinderziekenhuis ( Site 4228)	Utrecht
Peru	Instituto Nacional Cardiovascular Incor ( Site 3928)	Lima
Russian Federation	Scientific Research Institute Complex Problems Cardiovascular Disease ( Site 4288)	Kemerovo	Kemerovskaya Oblast
Russian Federation	Children City Clinical Hospital #9 n.a. G.N.Speransky ( Site 4290)	Moscow	Moskva
Russian Federation	Children City Clinical Hospital 13 n.a N.F.Filatov ( Site 4285)	Moscow	Moskva
Russian Federation	NMRC Obstetrics Gynecology and Perinatology n.a. V.I. Kulakov ( Site 4287)	Moscow	Moskva
Russian Federation	Pediatric Hematology Oncology and Immunology Centre n.a. D.Rogachev. ( Site 4275)	Moscow	Moskva
Russian Federation	Scientific-Research Clinical Pediatric Institution n.a. Veltischev ( Site 4276)	Moscow	Moskva
Russian Federation	St.Petersburg State Pediatric Medical University ( Site 4281)	Saint Petersburg	Sankt-Peterburg
United States	University of Vermont Medical Center ( Site 3013)	Burlington	Vermont
United States	McGovern Medical School at UT Health/ Memorial Hermann ( Site 3014)	Houston	Texas
United States	Variety Children's Hospital D.B.A. Nicklaus Children's Hospital ( Site 3019)	Miami	Florida
United States	OU Medical Center ( Site 3005)	Oklahoma City	Oklahoma
United States	Lucille Packard Children's Hospital ( Site 3008)	Palo Alto	California
United States	The Children's Hospital of Philadelphia ( Site 3021)	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh UPMC ( Site 3017)	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Denmark,  Finland,  France,  Guatemala,  Hungary,  Malaysia,  Mexico,  Netherlands,  Peru,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A. Area Under the Plasma Concentration Time Curve (AUC) for Sugammadex	The AUC for sugammadex in plasma will be calculated.	Baseline and 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
Primary	Part A. Plasma Clearance (CL) of Sugammadex	The CL for sugammadex will be calculated.	Baseline and 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
Primary	Part A. Apparent Volume of Distribution (Vz) for Sugammadex	The Vz for sugammadex will be calculated.	Baseline and 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
Primary	Part A. Apparent Volume of Distribution at Steady State (Vss) for Sugammadex	The Vss for sugammadex will be calculated.	Baseline and 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
Primary	Part A. Maximum Plasma Concentration (Cmax) of Sugammadex	The Cmax for sugammadex will be calculated.	Baseline and 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
Primary	Part A. Half-Life (t1/2) of Sugammadex in Plasma	The t1/2 for sugammadex will be calculated.	Baseline and 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
Primary	Part B. Time to Neuromuscular Recovery	Time to neuromuscular recovery will be reported, defined as the interval from administration of reversal agent to time to neuromuscular recovery.	Within Day 1
Primary	Parts A and B. Adverse Events (AEs)	The number of participants experiencing an AE will be reported.	Up to 7 days
Secondary	Part B. Time to Extubation	Time to extubation will be reported, defined as the interval from administration of reversal agent to removal of the endotracheal tube.	Within Day 1

External Links

•   Merck Clinical Trials Information