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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 4

Conditions: Neuromuscular Blockade

Treatments: Drug: Sugammadex 2 mg/kg; Drug: Sugammadex 4 mg/kg; Drug: Neostigmine + Glycopyrrolate; Drug: Neostigmine + Atropine

Study type: Interventional

Funder types: Industry

Identifiers

NCT03909165

2017-000693-11 (EudraCT Number)

8616-169

MK-8616-169 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 145 patients

Sex: All

Ages: 1 day to 2 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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145 participants in 5 patient groups

Part A. Sugammadex 2 mg/kg

Experimental group

Description:

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

Treatment:

Drug: Sugammadex 2 mg/kg

Part A. Sugammadex 4 mg/kg

Experimental group

Description:

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

Treatment:

Drug: Sugammadex 4 mg/kg

Part B. Sugammadex 2 mg/kg

Experimental group

Description:

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

Treatment:

Drug: Sugammadex 2 mg/kg

Part B. Sugammadex 4 mg/kg

Experimental group

Description:

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

Treatment:

Drug: Sugammadex 4 mg/kg

Part B. Neostigmine

Active Comparator group

Description:

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.

Treatment:

Drug: Neostigmine + Atropine

Drug: Neostigmine + Glycopyrrolate