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ObesityPhase 4CURESNCT01748643

CURES: The Effect of Deep Curarisation and Reversal With Sugammadex on Surgical Conditions and Perioperative Morbidity

A Phase 4 study testing deep neuromuscular blockade with rocuronium, reversal with sugammadex and normal neuromuscular blockade reversal with rocuronium, reversal with neostigmine in people with Obesity and Laparoscopic Gastric Bypass Surgery, run by Ziekenhuis Oost-Limburg at 1 site in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to investigate if a deep neuromuscular block with a continuous infusion of rocuronium titrated to a post-tetanic count (PTC) of 1-2 responses combined with reversal of neuromuscular blockade with sugammadex results in improved surgical conditions for the surgeon and/or improved… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
deep neuromuscular blockade with rocuronium, reversal with sugammadex and normal neuromuscular blockade reversal with rocuronium, reversal with neostigmine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteBelgium
Study dates
Apr 2013to Jan 2015
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Able to give written informed consent
  • American Society of Anaesthesiologists class I, II or III
  • Obese or morbid obese as defined by BMI > 30 and >40 kg/m2 respectively

Who cannot join

  • Neuromuscular disorders
  • Allergies to, or contraindication for muscle relaxants, neuromuscular reversing agents, anaesthetics, narcotics
  • Malignant hyperthermia
  • Pregnancy or lactation
  • Renal insufficiency defined as serum creatinine of 2x the upper normal limit, glomerular filtration rate < 60ml/min, urine output of < 0.5ml/kg/h for at least 6h
  • Chronic obstructive pulmonary disease GOLD classification 2 or higher.
Show all 10Show fewer
  • Clinical, radiographic or laboratory findings suggesting upper or lower airway infection
  • Congestive heart failure.
  • Pickwick syndrome
  • Psychiatric illness inhibiting cooperation with study protocol or possibly obscuring results

Trial locations and contacts

1 site in 1 country.

Belgium1 site

  • Ziekenhuis Oost-Limburg

    Genk, Limburg, 3600

Other trials in Belgium

About this study

Official title: Effect of Deep Curarisation and Reversal With Sugammadex on Surgical Conditions and Perioperative Morbidity in Patients Undergoing Laparoscopic Gastric Bypass Surgery

The purpose of this study is to investigate if a deep neuromuscular block with a continuous infusion of rocuronium titrated to a post-tetanic count (PTC) of 1-2 responses combined with reversal of neuromuscular blockade with sugammadex results in improved surgical conditions for the surgeon and/or improved post-operative respiratory function for the patients as compared to a standard technique with an intubation dose of rocuronium and top-ups as needed to maintain a neuromuscular blockade with a train of four (TOF) count of 1-2 and reversal of neuromuscular blockade with neostigmine/glycopyrrolate.

Furthermore, we want to investigate the effect of pneumoperitoneum, and NMB with rocuronium and reversal with sugammadex or neostigmine/glycopyrrolate on cerebral tissue oxygenation.

Read the detailed description

Laparoscopic bariatric surgery poses special demands on the anaesthesiologist as well as the surgeon. The surgeon requires good visualisation of the operative field while the anaesthesiologist is concerned with adequate postoperative respiratory function in these morbidly obese patients. With the advent of advanced laparoscopic techniques the time span between adequate neuromuscular blockade (NMB) and adequate postoperative recovery of respiratory muscle function is growing ever shorter with an increasing risk of postoperative residual NMB.

Even minimal postoperative residual NMB with a train of four ratio (TOF) of 0.8 is associated with impaired respiratory function as witnessed in reductions of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) in healthy volunteers. Moreover, a TOF < 0.7 correlates with increased postoperative respiratory complications due to the inability to swallow normally leading to aspiration, atelectasis and pneumonia. However, neuromuscular blocking agents not only impair respiratory function due to skeletal muscle relaxation. Also the body's response to hypoxia is impeded due to carotid body chemoreceptor suppression. Worryingly, reversal of NMB with neostigmine can lead to respiratory complications such as bronchospasm and even induce neuromuscular transmission failure in patients who already recovered from NMB.

Obese patients are at even greater risk for postoperative respiratory complications. In a recent study after bariatric surgery, 100% of patients had at least one hypoxic event (oxygen saturation <90% more then 30seconds). Restrictive ventilatory defects are clearly associated with body mass index (BMI) and obesity hypoventilation syndrome. Since respiratory failure is responsible for 11.8% of mortalities after bariatric surgery, optimal respiratory care for these patients is primordial. Optimal reversal of NMB plays an important role herein. With the advent of Sugammadex, a cyclodextrin molecule that encapsulates and inactivates rocuronium and vecuronium, rapid and dose-dependent reversal of profound NMB by high dose rocuronium is possible without the risk of impaired upper airway dilator muscle activity when given after recovery from NMB.

Furthermore, little is known about the cerebral tissue oxygen saturation (SctO2) in these morbidly obese patients during laparoscopic gastric bypass surgery. Since the unexpected finding that NMB influences hypoxic ventilatory response, more research is needed into the effect of neuromuscular blockers and their reversing agents on cerebral oxygenation. Using near infrared spectroscopy (Fore-sight®) technology absolute brain tissue oxygenation can be quantified to study these effects.

In this study we wish to investigate if a deep neuromuscular block with a continuous infusion of rocuronium titrated to a post-tetanic count (PTC) of 1-2 responses combined with reversal of NMB with sugammadex results in:

  1. Improved surgical conditions for the surgeon ii. Improved post-operative respiratory function for the patients as compared to a standard technique with an intubation dose of rocuronium and top-ups as needed to maintain a NMB with a TOF count of 1-2 and reversal of NMB with neostigmine/glycopyrrolate.

Furthermore, we wish to investigate the effect of pneumoperitoneum, and NMB with rocuronium and reversal with Sugammadex or neostigmine/glycopyrrolate on cerebral tissue oxygenation.

Being tested
deep neuromuscular blockade with rocuronium, reversal with sugammadex, normal neuromuscular blockade reversal with rocuronium, reversal with neostigmine
Medical subject headings
Obesity, Respiratory Aspiration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • deep neuromuscular blockade with rocuronium, reversal with sugammadexDrug

    Also called rocuronium: Esmeron, sugammadex: Bridion

    after induction of anesthesia, a rocuronium infusion (0.6mg/kg (lean body mass)/h,) is started and titrated to a post tetanic count of 1-2 twitches. At the end of surgery neuromuscular blockade will be reversed with sugammadex 4mg/kg. Patients are extubated when TOF ratio > 0.9.

  • normal neuromuscular blockade reversal with rocuronium, reversal with neostigmineDrug

    Also called rocuronium: Esmeron, neostigmine, glycopyrrolate

    After induction of anesthesia, top-ups of rocuronium (10mg) are given as needed to maintain a train of four count of 1-2. At the end of surgery neuromuscular blockade will be reversed with neostigmine 50μg/kg and glycopyrrolate 10μg/kg (lean body mass). Patients are extubated when the train of four ratio is > 0.9.

Study groups in NCT01748643
Study groupRoleWhat they receive
Deep neuromuscular blockade, reversal with sugammadexExperimentala continuous rocuronium infusion (0.6mg/kg (lean body mass)/h,) is started and titrated to a post tetanic count of 1-2 twitches. At the end of surgery neuromuscular blockade will be reversed with Sugammadex 4mg/kg. Patients are extubated when the train of four ratio is > 0.9.
Receives: Drug: deep neuromuscular blockade with rocuronium, reversal with sugammadex
normal neuromuscular blockade, reversal with neostigmineActive comparatorAfter induction of anesthesia, top-ups of rocuronium (10mg) are given as needed to maintain a train of four count of 1-2. At the end of surgery neuromuscular blockade will be reversed with neostigmine 50μg/kg and glycopyrrolate 10μg/kg (lean body mass). Patients are extubated when TOF ratio > 0.9.
Receives: Drug: normal neuromuscular blockade reversal with rocuronium, reversal with neostigmine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Subjective Evaluation of the View on the Operating Field by the Surgeon

    At the end of surgery, the view on the operating field will be graded by the surgeon using a 5-point rating scale:

    1. Extremely poor
    2. Poor
    3. Acceptable
    4. Good
    5. Optimal

    Measured: Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h

  2. Number of Intra-abdominal Pressure Rises > 18cmH2O

    The number of intra-abdominal pressure rises > 18cmH2O detected by the intra-abdominal CO2 insufflator.

    Measured: Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h

  3. Duration of Surgery

    Measured from the time of first skin incision to completion of skin closure.

    Measured: Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h

Secondary outcomes (3)

  1. Peak Expiratory Flow

    Peak expiratory flow is measured with the Vitalograph® electronic portable peak flow meter. A mean of 3 measurements in the upright posture in bed before and after surgery will be used.

    Measured: Measured the day before surgery and 30min after completion of surgery (when the modified observer's assessment of alertness/sedation scale is 5 (Patient responds readily to name spoken in normal tone))

  2. Forced Expiratory Volume in 1 Second

    Forced expiratory volume in 1 second is measured with the Vitalograph® electronic portable peak flow meter. A mean of 3 measurements in the upright posture in bed before and after surgery will be used.

    Measured: Measured the day before surgery and 30min after completion of surgery (when the modified observer's assessment of alertness/sedation scale is 5 (Patient responds readily to name spoken in normal tone))

  3. Forced Vital Capacity

    Forced vital capacity is measured with the Vitalograph® electronic portable peak flow meter. A mean of 3 measurements in the upright posture in bed before and after surgery will be used.

    Measured: Measured the day before surgery and 30min after completion of surgery (when the modified observer's assessment of alertness/sedation scale is 5 (Patient responds readily to name spoken in normal tone))

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Dec 2012 (estimated)
  2. Study startApr 2013
  3. Primary completionJan 2015
  4. Study completionJan 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01748643
Sponsor's protocol ID
PVRA-01
Other IDs
2012-005533-37, 8616-085MISP
Acronym
CURES
Status last verified
Apr 2017
First submitted
6 Dec 2012
Last updated
3 Aug 2017
Data monitoring committee
No

Publications

  • Ali HH, Wilson RS, Savarese JJ, Kitz RJ. The effect of tubocurarine on indirectly elicited train-of-four muscle response and respiratory measurements in humans. Br J Anaesth. 1975 May;47(5):570-4. doi: 10.1093/bja/47.5.570.

    PubMed 1138775

  • Eikermann M, Groeben H, Husing J, Peters J. Accelerometry of adductor pollicis muscle predicts recovery of respiratory function from neuromuscular blockade. Anesthesiology. 2003 Jun;98(6):1333-7. doi: 10.1097/00000542-200306000-00006.

    PubMed 12766640

  • Berg H, Roed J, Viby-Mogensen J, Mortensen CR, Engbaek J, Skovgaard LT, Krintel JJ. Residual neuromuscular block is a risk factor for postoperative pulmonary complications. A prospective, randomised, and blinded study of postoperative pulmonary complications after atracurium, vecuronium and pancuronium. Acta Anaesthesiol Scand. 1997 Oct;41(9):1095-1103. doi: 10.1111/j.1399-6576.1997.tb04851.x.

    PubMed 9366929

  • Sundman E, Witt H, Olsson R, Ekberg O, Kuylenstierna R, Eriksson LI. The incidence and mechanisms of pharyngeal and upper esophageal dysfunction in partially paralyzed humans: pharyngeal videoradiography and simultaneous manometry after atracurium. Anesthesiology. 2000 Apr;92(4):977-84. doi: 10.1097/00000542-200004000-00014.

    PubMed 10754616

  • Murphy GS, Szokol JW, Marymont JH, Greenberg SB, Avram MJ, Vender JS. Residual neuromuscular blockade and critical respiratory events in the postanesthesia care unit. Anesth Analg. 2008 Jul;107(1):130-7. doi: 10.1213/ane.0b013e31816d1268.

    PubMed 18635478

  • Eriksson LI. Reduced hypoxic chemosensitivity in partially paralysed man. A new property of muscle relaxants? Acta Anaesthesiol Scand. 1996 May;40(5):520-3. doi: 10.1111/j.1399-6576.1996.tb04482.x.

    PubMed 8792879

  • Wyon N, Joensen H, Yamamoto Y, Lindahl SG, Eriksson LI. Carotid body chemoreceptor function is impaired by vecuronium during hypoxia. Anesthesiology. 1998 Dec;89(6):1471-9. doi: 10.1097/00000542-199812000-00025.

    PubMed 9856722

  • Pratt CI. Bronchospasm after neostigmine. Anaesthesia. 1988 Mar;43(3):248. doi: 10.1111/j.1365-2044.1988.tb05560.x. No abstract available.

    PubMed 3364648

  • Payne JP, Hughes R, Al Azawi S. Neuromuscular blockade by neostigmine in anaesthetized man. Br J Anaesth. 1980 Jan;52(1):69-76. doi: 10.1093/bja/52.1.69.

    PubMed 7378232

  • Gallagher SF, Haines KL, Osterlund LG, Mullen M, Downs JB. Postoperative hypoxemia: common, undetected, and unsuspected after bariatric surgery. J Surg Res. 2010 Apr;159(2):622-6. doi: 10.1016/j.jss.2009.09.003. Epub 2009 Sep 25.

    PubMed 20006346

  • Saliman JA, Benditt JO, Flum DR, Oelschlager BK, Dellinger EP, Goss CH. Pulmonary function in the morbidly obese. Surg Obes Relat Dis. 2008 Sep-Oct;4(5):632-9; discussion 639. doi: 10.1016/j.soard.2008.06.010. Epub 2008 Jul 17.

    PubMed 18722823

  • Puhringer FK, Rex C, Sielenkamper AW, Claudius C, Larsen PB, Prins ME, Eikermann M, Khuenl-Brady KS. Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points: an international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial. Anesthesiology. 2008 Aug;109(2):188-97. doi: 10.1097/ALN.0b013e31817f5bc7.

    PubMed 18648227

  • Eikermann M, Zaremba S, Malhotra A, Jordan AS, Rosow C, Chamberlin NL. Neostigmine but not sugammadex impairs upper airway dilator muscle activity and breathing. Br J Anaesth. 2008 Sep;101(3):344-9. doi: 10.1093/bja/aen176. Epub 2008 Jun 16.

    PubMed 18559352

  • Cohen LB, Delegge MH, Aisenberg J, Brill JV, Inadomi JM, Kochman ML, Piorkowski JD Jr; AGA Institute. AGA Institute review of endoscopic sedation. Gastroenterology. 2007 Aug;133(2):675-701. doi: 10.1053/j.gastro.2007.06.002. No abstract available.

    PubMed 17681185

  • Miller MR, Dickinson SA, Hitchings DJ. The accuracy of portable peak flow meters. Thorax. 1992 Nov;47(11):904-9. doi: 10.1136/thx.47.11.904.

    PubMed 1465746

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing deep neuromuscular blockade with rocuronium, reversal with sugammadex and normal neuromuscular blockade reversal with rocuronium, reversal with neostigmine in people with Obesity and Laparoscopic Gastric Bypass Surgery, run by Ziekenhuis Oost-Limburg at 1 site in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Subjective Evaluation of the View on the Operating Field by the Surgeon (time frame: Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01748643, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2017.

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