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

NCT ID: NCT03909165

Last Updated: 2025-07-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 145 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-23
• Study Completion Date: 2023-09-21

Brief 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.

Detailed 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.

Conditions

Neuromuscular Blockade

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part A. Sugammadex 2 mg/kg

Participants received a single intravenous (IV) bolus of sugammadex at 2 mg/kg for moderate NMB reversal.

Group Type: EXPERIMENTAL

Sugammadex 2 mg/kg

Intervention Type: DRUG

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.

Part A. Sugammadex 4 mg/kg

Participants received a single IV bolus of sugammadex at 4 mg/kg for deep NMB reversal.

Group Type: EXPERIMENTAL

Sugammadex 4 mg/kg

Intervention Type: DRUG

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).

Part B. Sugammadex 2 mg/kg

Participants received a single IV bolus of sugammadex at 2 mg/kg for moderate NMB reversal.

Group Type: EXPERIMENTAL

Sugammadex 2 mg/kg

Intervention Type: DRUG

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.

Part B. Sugammadex 4 mg/kg

Participants received a single IV bolus of sugammadex at 4 mg/kg for deep NMB reversal.

Group Type: EXPERIMENTAL

Sugammadex 4 mg/kg

Intervention Type: DRUG

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).

Part B. Neostigmine

Participants received a single IV 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) based on availability and/or contraindications, for moderate NMB reversal.

Group Type: ACTIVE_COMPARATOR

Neostigmine + Glycopyrrolate

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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).

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

MK-8616; MK-8616

Eligibility Criteria

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.

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Lucille Packard Children's Hospital ( Site 3008)

Palo Alto, California, 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

The Children's Hospital of Philadelphia ( Site 3021)

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh UPMC ( Site 3017)

Pittsburgh, Pennsylvania, United States

McGovern Medical School at UT Health/ Memorial Hermann ( Site 3014)

Houston, Texas, United States

University of Vermont Medical Center ( Site 3013)

Burlington, Vermont, United States

The Children s Hospital at Westmead ( Site 3805)

Westmead, New South Wales, Australia

Queensland Children s Hospital ( Site 3806)

South Brisbane, Queensland, Australia

Royal Childrens Hospital Melbourne ( Site 3801)

Parkville, Victoria, Australia

Universitaire Ziekenhuis Antwerpen - UZA ( Site 3200)

Edegem, Antwerpen, Belgium

UZ Brussel ( Site 3201)

Brussels, Bruxelles-Capitale, Region de, Belgium

UZ Leuven - Campus Gasthuisberg ( Site 3202)

Leuven, Vlaams-Brabant, Belgium

Hospital Pequeno Principe ( Site 3826)

Curitiba, Paraná, Brazil

Hospital Tacchini ( Site 3827)

Bento Gonçalves, Rio Grande do Sul, Brazil

Instituto da Crianca do Hospital das Clinicas-FMUSP ( Site 3825)

São Paulo, , Brazil

Rigshospitalet ( Site 3250)

Copenhagen, Capital Region, Denmark

New Childrens Hospital ( Site 3750)

Helsinki, Uusimaa, Finland

C.H.R.U. de Lille. Hopital Jeanne de Flandres ( Site 3304)

Lille, Nord, France

Unidad de Cirugía Cardiovascular ( Site 4126)

Guatemala City, , Guatemala

Szegedi Tudomanyegyetem ( Site 4201)

Szeged, Csongrád megye, Hungary

Debreceni Egyetem Klinikai Kozpont ( Site 4200)

Debrecen, , Hungary

Sarawak General Hospital ( Site 3877)

Kuching, Sarawak, Malaysia

Women and Children Hospital Kuala Lumpur (Hospital Tunku Azizah) ( Site 3875)

Kuala Lumpur, , Malaysia

University Malaya Medical Centre. ( Site 3876)

Kuala Lumpur, , Malaysia

Hospital General de Zona No. 1 ( Site 4153)

Ciudad de Villa de Álvarez, Colima, Mexico

Centenario Hospital Miguel Hidalgo-Pediatrics Department ( Site 4152)

Aguascalientes, , Mexico

Radboud University Medical Center ( Site 4226)

Nijmegen, Gelderland, Netherlands

Erasmus University Medical Center ( Site 4225)

Rotterdam, South Holland, Netherlands

University Medical Center Groningen ( Site 4227)

Groningen, , Netherlands

Wilhelmina Kinderziekenhuis ( Site 4228)

Utrecht, , Netherlands

Instituto Nacional Cardiovascular Incor ( Site 3928)

Lima, , Peru

Scientific Research Institute Complex Problems Cardiovascular Disease ( Site 4288)

Kemerovo, Kemerovo Oblast, Russia

NMRC Obstetrics Gynecology and Perinatology n.a. V.I. Kulakov ( Site 4287)

Moscow, Moscow, Russia

Pediatric Hematology Oncology and Immunology Centre n.a. D.Rogachev. ( Site 4275)

Moscow, Moscow, Russia

Children City Clinical Hospital 13 n.a N.F.Filatov ( Site 4285)

Moscow, Moscow, Russia

Children City Clinical Hospital #9 n.a. G.N.Speransky ( Site 4290)

Moscow, Moscow, Russia

Scientific-Research Clinical Pediatric Institution n.a. Veltischev ( Site 4276)

Moscow, Moscow, Russia

St.Petersburg State Pediatric Medical University ( Site 4281)

Saint Petersburg, Sankt-Peterburg, Russia

Countries

United States; Australia; Belgium; Brazil; Denmark; Finland; France; Guatemala; Hungary; Malaysia; Mexico; Netherlands; Peru; Russia

References

Mensah-Osman E, Mukai Y, Wang A, Matuszczak M, Saldien V, Leibensperger H, Speek M, Locco A, Wrishko R, Gee A, Herring WJ. Sugammadex for Reversal of Neuromuscular Blockade in Neonates and Infants Less than 2 Years Old: Results from a Phase IV Randomized Clinical Trial. Anesthesiology. 2025 Aug 1;143(2):300-312. doi: 10.1097/ALN.0000000000005535. Epub 2025 May 5.

Reference Type: RESULT

PMID: 40324166 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.merckclinicaltrials.com/

Merck Clinical Trials Information

Other Identifiers

MK-8616-169

Identifier Type: OTHER

Identifier Source: secondary_id

2017-000693-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8616-169

Identifier Type: -

Identifier Source: org_study_id