Effect of Neuromuscular Blockade and Reversal on Breathing

NCT02845375 | Completed Phase 4 Results DMC

• 1 other identifier: P16.025
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

In this study the investigators will assess (i) the effect of partial neuromuscular blockade (NMB; TOF ratio 0.8 and 0.6) induced by low-dose rocuronium on the ventilatory response to isocapnic hypoxia and (ii) the effect over time (from TOF 0.6 to TOF 1.0) of the reversal by sugammadex, neostigmine or placebo in healthy volunteers. Additionally the investigators will assess the effect of partial NMB (TOF ratio 0.6) induced by low-dose rocuronium on the ventilatory response to hypercapnia and effect over time (from TOF 0.6 to TOF 1.0) of the reversal by sugammadex, neostigmine or placebo in healthy volunteers.

Conditions

Respiratory Insufficiency

Outcome Measures

Primary Outcomes (2)

• Breathing Increase Due to a Reduction in Inspired Oxygen Saturation (Hypoxic Ventilatory Response)

  The change in breathing response to a decrease in inspired oxygen concentration, which equals the isocapnic ventilatory response to hypoxia.

  during the 1-2 hours following reversal

• Breathing Increase Due to a Reduction in Inspired Oxygen Saturation (Hypoxic Ventilatory Response)

  The ventilatory response to a decrease in oxygen saturaytion of 80%

  0-10 minutes following reversal

Study Arms (3)

PLACEBO

PLACEBO COMPARATOR

Placebo (normal saline) will be administered following a period of muscle relaxation after which respiratory measurements will be obtained.

Drug: Placebo

NEOSTIGMINE

OTHER

intravenous neostigmine will be administered following a period of muscle relaxation after which respiratory measurements will be obtained.

Drug: Neostigmine

SUGAMMADEX

EXPERIMENTAL

intravenous sugammade will be administered following a period of muscle relaxation after which respiratory measurements will be obtained.

Drug: Sugammadex

Interventions

Sugammadex DRUG

Sugammadex will be administered following a period of muscle relaxation after wich respiratory measurements will be obtained.

SUGAMMADEX

Neostigmine DRUG

Neostigmine will be administered following a period of muscle relaxation after wich respiratory measurements will be obtained.

Also known as: NEO

NEOSTIGMINE

Placebo DRUG

Placebo will be administered following a period of muscle relaxation after wich respiratory measurements will be obtained.

Also known as: Normal saline

PLACEBO

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• male gender
• age 18 years and older
• body mass index \< 30 kg/m2.

You may not qualify if:

• Known or suspected neuromuscular disorders impairing neuromuscular function;
• allergies to muscle relaxants, anesthetics or narcotics;
• a (family) history of malignant hyperthermia or any other muscle disease;
• any medical, neurological or psychiatric illness (including a history of anxiety).

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, South Holland, 2333 ZA, Netherlands

Location

Related Publications (3)

• Eriksson LI, Sato M, Severinghaus JW. Effect of a vecuronium-induced partial neuromuscular block on hypoxic ventilatory response. Anesthesiology. 1993 Apr;78(4):693-9. doi: 10.1097/00000542-199304000-00012.

  PMID: 8096684 BACKGROUND

• Eriksson LI, Lennmarken C, Wyon N, Johnson A. Attenuated ventilatory response to hypoxaemia at vecuronium-induced partial neuromuscular block. Acta Anaesthesiol Scand. 1992 Oct;36(7):710-5. doi: 10.1111/j.1399-6576.1992.tb03550.x.

  PMID: 1359723 BACKGROUND

• Dahan A, Nieuwenhuijs D, Teppema L. Plasticity of central chemoreceptors: effect of bilateral carotid body resection on central CO2 sensitivity. PLoS Med. 2007 Jul 24;4(7):e239. doi: 10.1371/journal.pmed.0040239.

  PMID: 17676946 BACKGROUND

MeSH Terms

Conditions

Respiratory Insufficiency

Interventions

Sugammadex; Neostigmine; Saline Solution

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates; Phenylammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

There were no perceived limitations or caveats

Results Point of Contact

• Title: Dr Albert Dahan
• Organization: Leiden University Medical Center

a.dahan@lumc.nl

+31715262301

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 14, 2016
• First Posted: July 27, 2016
• Study Start: September 1, 2016
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: February 19, 2020
• Results First Posted: February 19, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: Mid 2019
• Access Criteria: Request to the authors and approved protocol for data analysis to be submitted. A review committee will then decide wether the data will be shared, deepening on supplementary data analyses by the authors

Locations

NL (1)