Adult Subjects Undergoing Abdominal Surgery Under General Anesthesia Clinical Trial
Official title:
Randomized, Parallel-group, Placebo-controlled, Safety-assessor Blinded Trial in Adult Subjects Evaluating the Efficacy and Safety of Sugammadex for Reversal of Pipecuronium-induced Neuromuscular Blockade in Subjects Undergoing Abdominal Surgery Under General Anesthesia
Primary objectives:
1. to investigate the efficacy of sugammadex in dose of 4 mg/kg administered at
reappearance of T2 for reversal of pipecuronium-induced neuromuscular blockade in
subjects undergoing abdominal surgery under general anesthesia
2. to evaluate the safety and tolerability of a single dose of 4 mg/kg sugammadex
administered at reappearance of T2 for reversal of pipecuronium-induced neuromuscular
blockade
Secondary objectives:
1. to evaluate the time from the start of sugammadex or placebo administration to the time
of extubation and to the time of recovery of TOF ratio to ≥ 0.9
Exploratory objectives:
1. to evaluate the Operating Room (OR) and Post Anesthetic Care Unit (PACU) length of stay
after the end of surgery in subjects with pipecuronium induced neuromuscular blockade
reversed by 4.0 mg.kg-1 sugammadex compared to placebo (saline)
2. compare the number of patients extubated in the OR after the reversal by sugammadex or
placebo, evaluate the TOF ratio at the time of extubation
Clinical hypothesis:
1. Sugammadex has to be effective and well tolerated for reversal of pipecuronium-induced
blockade
Sugammadex is the first selective relaxant binding agent indicated for reversal of
rocuronium and vecuronium-induced blockade.
At the same time sugammadex is able to form the complexes with other aminosteroid-based
muscle relaxants including long acting NMBAs* such as pancuronium 1,2.
Still there are only limited data on the efficacy of sugammadex with pancuronium and no data
on the efficacy of sugammadex with other aminosteroid-based long acting NMBA - pipecuronium
which is still widely used in Russia (as well as in the other former Soviet Union Countries
and Eastern Europe countries). In the only study evaluating efficacy of sugammadex with
pancuronium has been shown that moderate pancuronium-induced blockade is effectively
reversed in less than 3 minutes with a sugammadex dose of 4.0 mg/kg 3. In this respect it
would be interesting in this study to evaluate the efficacy of sugammadex with pipecuronium.
It is also very well known that the incidence of postoperative residual blockade (and its
complications) is higher when the long acting NMBAs such as pancuronium and pipecuronium are
used 4,5,6,7. So the possibility to use sugammadex for reversal of pipecuronium-induced
blockade could help to reduce the incidence of residual blockade and related complications.
The effectiveness of sugammadex for the reversal of long acting NMBAs such as pipecuronium
at the same time would be significant in light of the limitations of cholinesterase
inhibitors. These drugs are more often administered after the long acting NMBAs taking into
account their prolonged clinical duration of action.
It is expected that the dose of sugammadex 4 mg/kg will allow to recover the TOF ratio to
0.9 in less than 4 min and in this case this time will be similar to the recovery time after
moderate pancuronium-induced blockade.
*NMBAs-neuromuscular blocking agents
2.3 Study Design
1. A single center, randomized, parallel-group, placebo-controlled, safety-assessor
(single) blinded trial
2. Adult patients undergoing abdominal surgery under general anesthesia who receive
succinylcholine for tracheal intubation and pipecuronium for maintenance of
neuromuscular blockade. Planned number of subjects - 42
3. Patients will be randomised into 2 groups to receive at the end of surgery 4 mg/kg of
sugammadex or 3 ml of saline (placebo) for reversal of pipecuronium-induced
neuromuscular blockade. According to the sample size justification randomization will
be done with the ratio of 1:2 - 14 patients will be enrolled in the placebo group and
28 patients - in sugammadex group
4. Neuromuscular function will be monitored using the objective neuromuscular monitoring
with the TOF-Watch® SX acceleromyograph at the adductor pollicis muscle, starting after
induction of anesthesia (before succinylcholine and pipecuronium administration) and
continuing at least until recovery of the TOF ratio to 0.9
5. The primary efficacy variable is the time from the start of sugammadex or placebo
administration (reappearance of T2) to recovery of the TOF ratio to 0.9
6. The secondary efficacy variable is the time from the start of sugammadex or placebo
administration to the time of extubation
7. Safety assessment is going to be done in order to evaluate the safety and tolerability
of sugammadex for reversal of pipecuronium-induced neuromuscular blockade (analysis of
AEs and vital signs)
Safety variables:
- Vital signs, i.e. heart rate and blood pressure (at screening, pre-pipecuronium,
pre-sugammadex or pre-placebo, at 2, 5, 10, and 30 minutes post-sugammadex or
post-placebo, and at the post-anesthetic visit)
- Physical examination (at screening, at the post-anesthetic visit)
- Pre-treatment (serious) events (from signing informed consent until administration
of sugammadex or placebo) and (serious) adverse events ((S)AEs, from
administration of sugammadex or placebo up to the end of trial)
8. Descriptive Variables:
- Time from OR admission (physical placement of subject into the OR) to actual OR
discharge
- Time from start of sugammadex or placebo administration to actual OR discharge
- Time from tracheal extubation to actual OR or PACU discharge
- Time from PACU admission to actual PACU discharge
- Number of patients extubated in the OR in both groups
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment