Recovery of Diaphragmatic Function After Neuromuscular Blockade and Sugammadex

NCT01962298 | Completed Phase 3 Results DMC

• 3 other identifiers: EC 13/5/602013-001926-25B300201316844
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

The effect of neuromuscular blocking agents (NMBA, e.g. rocuronium) on respiratory muscle activity is well known. However, since the availability of sugammadex, to our knowledge, no study has been conducted to evaluate the effect of this novel product on these muscles. Our hypothesis is that by applying a different strategy in the use of neuromuscular blocking agents and their reversal agents we might see a different activity of the respiratory muscles.

Conditions

Diaphragmatic Dysfunction; Muscle Weakness; Muscle Fatigue

Outcome Measures

Primary Outcomes (1)

• Electric Activity of the Diaphragm (Microvolts)

  From the start of spontaneous breathing till extubation, limited to maximum ten minutes after the onset of spontaneous breathing

Secondary Outcomes (1)

• Electric Activity of the Intercostal Muscles

  From the start of spontaneous breathing till extubation, limited to maximum ten minutes after the onset of spontaneous breathing

Other Outcomes (1)

• Centroid Frequency of the EMG, as Trend Variability (Change in %) From First to Last Recording

  From the start of spontaneous breathing till extubation, limited to maximum one hour after the onset of spontaneous breathing

Study Arms (5)

Single rocuronium dose - placebo

PLACEBO COMPARATOR

The patients will receive a single rocuronium dose, and no reversal agent.

Drug: placebo; Drug: Single rocuronium dose

Single rocuronium dose - sugammadex

ACTIVE COMPARATOR

The patients will receive a single rocuronium dose and sugammadex 2mg/kg as a reversal agent

Drug: sugammadex 2mg/kg; Drug: Single rocuronium dose

Repeated rocuronium dose - neostigmine

ACTIVE COMPARATOR

The patients will receive multiple rocuronium doses and neostigmine 70 mcg/kg as a reversal agent

Drug: neostigmine; Drug: Repeated rocuronium dose

Repeated rocuronium dose - sugammadex

ACTIVE COMPARATOR

The patients will receive multiple rocuronium doses and neostigmine 2mg/kg as a reversal agent

Drug: sugammadex 2mg/kg; Drug: Repeated rocuronium dose

Continuous rocuronium dose

ACTIVE COMPARATOR

The participants will receive a continuous rocuronium infusion and sugammadex 4 mg/kg as a reversal agent

Drug: sugammadex 4mg/kg; Drug: Continuous rocuronium infusion

Interventions

sugammadex 2mg/kg DRUG

Repeated rocuronium dose - sugammadex; Single rocuronium dose - sugammadex

neostigmine DRUG

Repeated rocuronium dose - neostigmine

sugammadex 4mg/kg DRUG

Continuous rocuronium dose

placebo DRUG

Single rocuronium dose - placebo

Single rocuronium dose DRUG

Single rocuronium dose - placebo; Single rocuronium dose - sugammadex

Repeated rocuronium dose DRUG

Repeated rocuronium dose - neostigmine; Repeated rocuronium dose - sugammadex

Continuous rocuronium infusion DRUG

Continuous rocuronium dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Each participant must have the mental capacity to decide whether he/she takes part in the trial or not. Each participant must voluntarily give his/her written informed consent. In case a participant is physically unable to give a written informed consent, a legal representative is to perform this.
• Each participant must be at least eighteen years of age. Participants can be of either sex and of any ethnical background.
• Each participant must meet the American Society of Anesthesiologists class II, II or III criteria.
• Each participant must be scheduled for intracranial surgery. During general anesthesia rocuronium must be used as a neuromuscular blocking agent.
• Each participant must be a suitable candidate for the rapid reversal of the neuromuscular blockade.
• Each female participant of sexually active age and of childbearing potential must agree to the use of a medically accepted method of contraception through seven days after the day of surgery. Postmenopausal (defined as at least twelve consecutive months without spontaneous menstrual period) women are not obliged to use contraceptives.

You may not qualify if:

• The participant is known or suspected to have a neuromuscular disorder.
• The participant is known or suspected to have an allergic reaction to sugammadex, rocuronium, anesthetic or narcotic medications, or any drugs used during general anesthesia.
• The participant is known or suspected to have an anatomical malformation impeding a proper intubation.
• The participant is known or suspected to have a history of malignant hyperthermia.
• The participant is pregnant (or intends to become pregnant within the presurgical period) or lactating.
• The participant is known to have a renal insufficiency (defined as a serum creatinine concentration of two times the upper limit, or a glomerular filtration rate of less than 60 ml/min).
• The participant is known or suspected to have a chronic obstructive pulmonary disease GOLD classification 2 or higher or has any respiratory disease that impairs his respiratory function to a NYHA III level or worse.
• The participant is known to have an infection of the upper or lower airways, as diagnosed by clinical or laboratory findings.
• The participant is known or suspected to have congestive heart failure.
• The participant is obese, as defined by a body mass index of 30 kg/m2 or more.
• The participant is known or suspected to have a major hepatic dysfunction.
• The participant has received or is scheduled to receive toremifene and/or an intravenous administration of fusidic acid within a time span of twenty-four hours before and twenty-four hours after the surgery.
• The participant is known or suspected to have any condition contraindicating the administration of sugammadex, neostigmine, glycopyrrolate or placebo.
• The participant is known or suspected to be directly involved in this study and/or is employed by or is a family member of any person employed by the investigator, at the investigational site, or by the sponsor.

Sponsors & Collaborators

• University Hospital, Antwerp: lead

Study Sites (1)

Antwerp University Hospital

Edegem, Antwerpen, 2650, Belgium

Location

Related Publications (2)

• Dres M, Schmidt M, Ferre A, Mayaux J, Similowski T, Demoule A. Diaphragm electromyographic activity as a predictor of weaning failure. Intensive Care Med. 2012 Dec;38(12):2017-25. doi: 10.1007/s00134-012-2700-3. Epub 2012 Sep 26.

  PMID: 23011532 BACKGROUND

• Schepens T, Janssens K, Maes S, Wildemeersch D, Vellinga J, Jorens PG, Saldien V. Respiratory muscle activity after spontaneous, neostigmine- or sugammadex-enhanced recovery of neuromuscular blockade: a double blind prospective randomized controlled trial. BMC Anesthesiol. 2019 Oct 19;19(1):187. doi: 10.1186/s12871-019-0863-y.

  PMID: 31629404 DERIVED

MeSH Terms

Conditions

Muscle Weakness

Interventions

Sugammadex; Neostigmine

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

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

Results Point of Contact

• Title: Dr Tom Schepens
• Organization: Antwerp University Hospital

tom.schepens@uza.be

003238213265

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Tom Schepens, MD

Study Record Dates

• First Submitted: October 9, 2013
• First Posted: October 14, 2013
• Study Start: October 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: October 24, 2018
• Results First Posted: October 24, 2018

Record last verified: 2018-03

Locations

BE (1)