Anesthesia
Conditions
Brief summary
The primary purpose of this study is to determine the dose requirements of rocuronium bromide when administered as a bolus dose (a single, large dose) for intubation (insertion of a tube through the nose or mouth into the trachea to provide artificial ventilation) and when administered by either continuous infusion or bolus doses for maintenance of muscle relaxation in term neonates (birth to \<28 days old), infants (28 days to \<=3 months) and toddlers (\>3 months to \<=2 years), children (2 years to less than or equal to 11 years of age), and adolescents (\>11 years to less than or equal to 17 years of age).
Interventions
DRUGRocuronium bolus maintenance
Subjects received a bolus dose of rocuronium for intubation followed by bolus doses for maintenance of muscle relaxation
DRUGrocuronium continuous infusion maintenance
Subjects received a bolus dose of rocuronium for intubation followed by continuous infusion of rocuronium for maintenance of muscle relaxation
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male and female subjects from birth up to 17 years of age who are scheduled for surgery with an anticipated duration of anesthesia of about 2 hours or more requiring a maintenance muscle relaxation dose(s).
Exclusion criteria
* Subjects whose parent(s) or legal guardian(s) are not willing to give written consent and where applicable, subjects who have not given appropriate assent to participate in the trials will not be allowed to enter.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Dose of Zemuron (Rocuronium) Administered | during surgery | Total dose from administration of intubating dose to reappearance of T3 (the third twitch of a Train of Four \[TOF\] stimulation) after the last maintenance bolus dose or discontinuation of Zemuron (rocuronium) infusion (Per protocol \[PP\] data set) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Recovery of T4/T1 Ratio (TOF Fourth Twitch to First Twitch) 70% | after surgery, from the reappearance of T3 after Zemuron(R) (rocuronium) infusion/last bolus dose of Zemuron(R) (rocuronium) | The time it takes for the the T4 to T1 ratio to reach 70%. The T4/T1 ratio is indicative of recovery. At complete recovery, the T4/T1 ratio is 1.0 (100%). |
| Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 80% | after surgery, from the reappearance of T3 after Zemuron(R) (rocuronium) infusion/last bolus dose of Zemuron(R) (rocuronium) | The time it takes for the the T4 to T1 ratio to reach 80%. The T4/T1 ratio is indicative of recovery. At complete recovery, the T4/T1 ratio is 1.0 (100%). |
| Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 90% | after surgery, from the reappearance of T3 after Zemuron(R) (rocuronium) infusion/last bolus dose of Zemuron(R) (rocuronium) | The time it takes for the the T4 to T1 ratio to reach 90%. The T4/T1 ratio is indicative of recovery. At complete recovery, the T4/T1 ratio is 1.0 (100%). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rocuronium Bolus Maintenance - Neonate (BN) Neonate subjects that received a bolus dose of rocuronium for intubation followed by bolus doses for maintenance of muscle relaxation | 5 |
| Rocuronium Bolus Maintenance - Infants (BI) Infant subjects that received a bolus dose of rocuronium for intubation followed by bolus doses for maintenance of muscle relaxation | 6 |
| Rocuronium Bolus Maintenance - Toddlers (BT) Toddler subjects that received a bolus dose of rocuronium for intubation followed by bolus doses for maintenance of muscle relaxation | 18 |
| Rocuronium Bolus Maintenance -Children (BC) Children subjects that received a bolus dose of rocuronium for intubation followed by bolus doses for maintenance of muscle relaxation | 18 |
| Rocuronium Bolus Maintenance - Adolescents (BA) Adolescent subjects that received a bolus dose of rocuronium for intubation followed by bolus doses for maintenance of muscle relaxation | 17 |
| Rocuronium Continuous Infusion Maintenance - Neonates (IN) Neonate subjects that received a bolus dose of rocuronium for intubation followed by continuous infusion of rocuronium for maintenance of muscle relaxation | 5 |
| Rocuronium Continuous Infusion Maintenance - Infants (II) Infant subjects that received a bolus dose of rocuronium for intubation followed by continuous infusion of rocuronium for maintenance of muscle relaxation | 6 |
| Rocuronium Continuous Infusion Maintenance - Toddlers (IT) Toddler subjects that received a bolus dose of rocuronium for intubation followed by continuous infusion of rocuronium for maintenance of muscle relaxation | 19 |
| Rocuronium Continuous Infusion Maintenance - Children (IC) Children subjects that received a bolus dose of rocuronium for intubation followed by continuous infusion of rocuronium for maintenance of muscle relaxation | 23 |
| Rocuronium Continuous Infusion Maintenance - Adolescents (IA) Adolescent subjects that received a bolus dose of rocuronium for intubation followed by continuous infusion of rocuronium for maintenance of muscle relaxation | 20 |
| Total | 137 |
Baseline characteristics
| Characteristic | Rocuronium Bolus Maintenance - Neonate (BN) | Rocuronium Bolus Maintenance - Infants (BI) | Rocuronium Bolus Maintenance - Toddlers (BT) | Rocuronium Bolus Maintenance -Children (BC) | Rocuronium Bolus Maintenance - Adolescents (BA) | Rocuronium Continuous Infusion Maintenance - Neonates (IN) | Rocuronium Continuous Infusion Maintenance - Infants (II) | Rocuronium Continuous Infusion Maintenance - Toddlers (IT) | Rocuronium Continuous Infusion Maintenance - Children (IC) | Rocuronium Continuous Infusion Maintenance - Adolescents (IA) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 5 Participants | 6 Participants | 18 Participants | 18 Participants | 17 Participants | 5 Participants | 6 Participants | 19 Participants | 23 Participants | 20 Participants | 137 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 1 Participants | 8 Participants | 6 Participants | 2 Participants | 3 Participants | 6 Participants | 11 Participants | 12 Participants | 52 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 17 Participants | 10 Participants | 11 Participants | 3 Participants | 3 Participants | 13 Participants | 12 Participants | 8 Participants | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 64 | 9 / 73 |
| serious Total, serious adverse events | 1 / 64 | 0 / 73 |
Outcome results
Primary
Total Dose of Zemuron (Rocuronium) Administered
Total dose from administration of intubating dose to reappearance of T3 (the third twitch of a Train of Four \[TOF\] stimulation) after the last maintenance bolus dose or discontinuation of Zemuron (rocuronium) infusion (Per protocol \[PP\] data set)
Time frame: during surgery
Population: Per protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rocuronium Bolus Maintenance - Neonate (BN) | Total Dose of Zemuron (Rocuronium) Administered | 0.91 mg/kg | Standard Deviation 0.17 |
| Rocuronium Bolus Maintenance - Infants (BI) | Total Dose of Zemuron (Rocuronium) Administered | 0.78 mg/kg | Standard Deviation 0.07 |
| Rocuronium Bolus Maintenance - Toddlers (BT) | Total Dose of Zemuron (Rocuronium) Administered | 0.86 mg/kg | Standard Deviation 0.18 |
| Rocuronium Bolus Maintenance -Children (BC) | Total Dose of Zemuron (Rocuronium) Administered | 0.81 mg/kg | Standard Deviation 0.1 |
| Rocuronium Bolus Maintenance - Adolescents (BA) | Total Dose of Zemuron (Rocuronium) Administered | 0.96 mg/kg | Standard Deviation 0.16 |
| Rocuronium Continuous Infusion Maintenance - Neonates (IN) | Total Dose of Zemuron (Rocuronium) Administered | 1.01 mg/kg | Standard Deviation 0.37 |
| Rocuronium Continuous Infusion Maintenance - Infants (II) | Total Dose of Zemuron (Rocuronium) Administered | 0.84 mg/kg | Standard Deviation 0.15 |
| Rocuronium Continuous Infusion Maintenance - Toddlers (IT) | Total Dose of Zemuron (Rocuronium) Administered | 1.00 mg/kg | Standard Deviation 0.25 |
| Rocuronium Continuous Infusion Maintenance - Children (IC) | Total Dose of Zemuron (Rocuronium) Administered | 1.26 mg/kg | Standard Deviation 0.78 |
| Rocuronium Continuous Infusion Maintenance - Adolescents (IA) | Total Dose of Zemuron (Rocuronium) Administered | 0.99 mg/kg | Standard Deviation 0.37 |
Secondary
Duration of Recovery of T4/T1 Ratio (TOF Fourth Twitch to First Twitch) 70%
The time it takes for the the T4 to T1 ratio to reach 70%. The T4/T1 ratio is indicative of recovery. At complete recovery, the T4/T1 ratio is 1.0 (100%).
Time frame: after surgery, from the reappearance of T3 after Zemuron(R) (rocuronium) infusion/last bolus dose of Zemuron(R) (rocuronium)
Population: per-protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rocuronium Bolus Maintenance - Neonate (BN) | Duration of Recovery of T4/T1 Ratio (TOF Fourth Twitch to First Twitch) 70% | 29.62 minutes | Standard Deviation 13.6 |
| Rocuronium Bolus Maintenance - Infants (BI) | Duration of Recovery of T4/T1 Ratio (TOF Fourth Twitch to First Twitch) 70% | 33.25 minutes | Standard Deviation 16.17 |
| Rocuronium Bolus Maintenance - Toddlers (BT) | Duration of Recovery of T4/T1 Ratio (TOF Fourth Twitch to First Twitch) 70% | 22.65 minutes | Standard Deviation 7.62 |
| Rocuronium Bolus Maintenance -Children (BC) | Duration of Recovery of T4/T1 Ratio (TOF Fourth Twitch to First Twitch) 70% | 16.19 minutes | Standard Deviation 6.7 |
| Rocuronium Bolus Maintenance - Adolescents (BA) | Duration of Recovery of T4/T1 Ratio (TOF Fourth Twitch to First Twitch) 70% | 28.04 minutes | Standard Deviation 13.33 |
| Rocuronium Continuous Infusion Maintenance - Neonates (IN) | Duration of Recovery of T4/T1 Ratio (TOF Fourth Twitch to First Twitch) 70% | 43.32 minutes | Standard Deviation 1.53 |
| Rocuronium Continuous Infusion Maintenance - Infants (II) | Duration of Recovery of T4/T1 Ratio (TOF Fourth Twitch to First Twitch) 70% | 33.25 minutes | Standard Deviation 0 |
| Rocuronium Continuous Infusion Maintenance - Toddlers (IT) | Duration of Recovery of T4/T1 Ratio (TOF Fourth Twitch to First Twitch) 70% | 23.08 minutes | Standard Deviation 13.4 |
| Rocuronium Continuous Infusion Maintenance - Children (IC) | Duration of Recovery of T4/T1 Ratio (TOF Fourth Twitch to First Twitch) 70% | 18.37 minutes | Standard Deviation 12.69 |
| Rocuronium Continuous Infusion Maintenance - Adolescents (IA) | Duration of Recovery of T4/T1 Ratio (TOF Fourth Twitch to First Twitch) 70% | 27.59 minutes | Standard Deviation 12.51 |
Secondary
Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 80%
The time it takes for the the T4 to T1 ratio to reach 80%. The T4/T1 ratio is indicative of recovery. At complete recovery, the T4/T1 ratio is 1.0 (100%).
Time frame: after surgery, from the reappearance of T3 after Zemuron(R) (rocuronium) infusion/last bolus dose of Zemuron(R) (rocuronium)
Population: per-protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rocuronium Bolus Maintenance - Neonate (BN) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 80% | 36.62 minutes | Standard Deviation 17.14 |
| Rocuronium Bolus Maintenance - Infants (BI) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 80% | 43.58 minutes | Standard Deviation 21.47 |
| Rocuronium Bolus Maintenance - Toddlers (BT) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 80% | 32.39 minutes | Standard Deviation 12.84 |
| Rocuronium Bolus Maintenance -Children (BC) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 80% | 20.43 minutes | Standard Deviation 9.79 |
| Rocuronium Bolus Maintenance - Adolescents (BA) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 80% | 35.75 minutes | Standard Deviation 19.43 |
| Rocuronium Continuous Infusion Maintenance - Neonates (IN) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 80% | 57.83 minutes | Standard Deviation 12.33 |
| Rocuronium Continuous Infusion Maintenance - Infants (II) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 80% | 44.75 minutes | Standard Deviation 0 |
| Rocuronium Continuous Infusion Maintenance - Toddlers (IT) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 80% | 29.47 minutes | Standard Deviation 16.65 |
| Rocuronium Continuous Infusion Maintenance - Children (IC) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 80% | 21.82 minutes | Standard Deviation 14.57 |
| Rocuronium Continuous Infusion Maintenance - Adolescents (IA) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 80% | 35.45 minutes | Standard Deviation 17.02 |
Secondary
Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 90%
The time it takes for the the T4 to T1 ratio to reach 90%. The T4/T1 ratio is indicative of recovery. At complete recovery, the T4/T1 ratio is 1.0 (100%).
Time frame: after surgery, from the reappearance of T3 after Zemuron(R) (rocuronium) infusion/last bolus dose of Zemuron(R) (rocuronium)
Population: per-protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rocuronium Bolus Maintenance - Neonate (BN) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 90% | 28.25 minutes | Standard Deviation 0 |
| Rocuronium Bolus Maintenance - Infants (BI) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 90% | 53.66 minutes | Standard Deviation 14.58 |
| Rocuronium Bolus Maintenance - Toddlers (BT) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 90% | 45.31 minutes | Standard Deviation 18.2 |
| Rocuronium Bolus Maintenance -Children (BC) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 90% | 23.09 minutes | Standard Deviation 10.9 |
| Rocuronium Bolus Maintenance - Adolescents (BA) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 90% | 49.25 minutes | Standard Deviation 31.73 |
| Rocuronium Continuous Infusion Maintenance - Neonates (IN) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 90% | 52.25 minutes | Standard Deviation 0 |
| Rocuronium Continuous Infusion Maintenance - Infants (II) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 90% | 50.75 minutes | Standard Deviation 0 |
| Rocuronium Continuous Infusion Maintenance - Toddlers (IT) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 90% | 37.86 minutes | Standard Deviation 18.46 |
| Rocuronium Continuous Infusion Maintenance - Children (IC) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 90% | 28.02 minutes | Standard Deviation 21.46 |
| Rocuronium Continuous Infusion Maintenance - Adolescents (IA) | Duration of Recovery of T4/T1 (TOF Fourth Twitch to First Twitch) Ratio 90% | 38.68 minutes | Standard Deviation 16.08 |