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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
First received
Last updated
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
Health authority
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.

Study Design


Related Conditions & MeSH terms


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
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