The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03909165




Registration number
NCT03909165
Ethics application status
Date submitted
8/04/2019
Date registered
9/04/2019
Date last updated
22/06/2020

Titles & IDs
Public title
Efficacy, Safety, and Pharmacokinetics of Sugammadex (MK-8616) for Reversal of Neuromuscular Blockade in Pediatric Participants Aged Birth to <2 Years (MK-8616-169)
Scientific 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
Secondary ID [1] 0 0
2017-000693-11
Secondary ID [2] 0 0
8616-169
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neuromuscular Blockade 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sugammadex 2 mg/kg
Treatment: Drugs - Sugammadex 4 mg/kg
Treatment: Drugs - Neostigmine + Glycopyrrolate
Treatment: Drugs - Neostigmine + Atropine

Experimental: Part A. Sugammadex 2 mg/kg - Single intravenous (IV) bolus of sugammadex at 2 mg/kg

Experimental: Part A. Sugammadex 4 mg/kg - Single IV bolus of sugammadex at 4 mg/kg.

Experimental: Part B. Sugammadex 2 mg/kg - Single IV bolus of sugammadex at 2 mg/kg.

Experimental: Part B. Sugammadex 4 mg/kg - Single IV bolus of sugammadex at 4 mg/kg.

Active Comparator: Part B. Neostigmine - 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).


Treatment: Drugs: 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.

Treatment: Drugs: 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).

Treatment: Drugs: 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.

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A. Area Under the Plasma Concentration Time Curve (AUC) for Sugammadex - The AUC for sugammadex in plasma will be calculated.
Timepoint [1] 0 0
Baseline and 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
Primary outcome [2] 0 0
Part A. Plasma Clearance (CL) of Sugammadex - The CL for sugammadex will be calculated.
Timepoint [2] 0 0
Baseline and 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
Primary outcome [3] 0 0
Part A. Apparent Volume of Distribution (Vz) for Sugammadex - The Vz for sugammadex will be calculated.
Timepoint [3] 0 0
Baseline and 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
Primary outcome [4] 0 0
Part A. Apparent Volume of Distribution at Steady State (Vss) for Sugammadex - The Vss for sugammadex will be calculated.
Timepoint [4] 0 0
Baseline and 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
Primary outcome [5] 0 0
Part A. Maximum Plasma Concentration (Cmax) of Sugammadex - The Cmax for sugammadex will be calculated.
Timepoint [5] 0 0
Baseline and 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
Primary outcome [6] 0 0
Part A. Half-Life (t1/2) of Sugammadex in Plasma - The t1/2 for sugammadex will be calculated.
Timepoint [6] 0 0
Baseline and 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
Primary outcome [7] 0 0
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.
Timepoint [7] 0 0
Within Day 1
Primary outcome [8] 0 0
Parts A and B. Adverse Events (AEs) - The number of participants experiencing an AE will be reported.
Timepoint [8] 0 0
Up to 7 days
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Within Day 1

Eligibility
Key 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.
Minimum age
No limit
Maximum age
2 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
The Children s Hospital at Westmead ( Site 3805) - Westmead
Recruitment hospital [2] 0 0
Royal Childrens Hospital Melbourne ( Site 3801) - Parkville
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Oklahoma
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Vermont
Country [7] 0 0
Belgium
State/province [7] 0 0
Bruxelles-Capitale, Region De
Country [8] 0 0
Denmark
State/province [8] 0 0
Hovedstaden
Country [9] 0 0
Finland
State/province [9] 0 0
Uusimaa
Country [10] 0 0
Malaysia
State/province [10] 0 0
Sarawak
Country [11] 0 0
Malaysia
State/province [11] 0 0
Wilayah Persekutuan Kuala Lumpur
Country [12] 0 0
Netherlands
State/province [12] 0 0
Zuid-Holland
Country [13] 0 0
Russian Federation
State/province [13] 0 0
Kemerovskaya Oblast'
Country [14] 0 0
Russian Federation
State/province [14] 0 0
Moskva
Country [15] 0 0
Russian Federation
State/province [15] 0 0
Sankt-Peterburg

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03909165
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@merck.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03909165