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Trial record 52 of 188 for:    GLYCOPYRROLATE

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

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ClinicalTrials.gov Identifier: NCT01748643
Recruitment Status : Completed
First Posted : December 12, 2012
Results First Posted : August 3, 2017
Last Update Posted : August 3, 2017
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Pascal Vanelderen, Ziekenhuis Oost-Limburg

Tracking Information
First Submitted Date  ICMJE December 6, 2012
First Posted Date  ICMJE December 12, 2012
Results First Submitted Date  ICMJE March 13, 2017
Results First Posted Date  ICMJE August 3, 2017
Last Update Posted Date August 3, 2017
Study Start Date  ICMJE April 2013
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 24, 2017)
  • 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 ]
    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
  • Number of Intra-abdominal Pressure Rises > 18cmH2O [ Time Frame: Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h ]
    The number of intra-abdominal pressure rises > 18cmH2O detected by the intra-abdominal CO2 insufflator.
  • Duration of Surgery [ Time Frame: Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h ]
    Measured from the time of first skin incision to completion of skin closure.
Original Primary Outcome Measures  ICMJE
 (submitted: December 10, 2012)
  • 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 ]
    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
  • Number of intra-abdominal pressure rises > 15cmH2O [ Time Frame: Participants will be followed for the duration of the laparoscopic gastric bypass surgery, an expected average of 1.5h ]
    The number of intra-abdominal pressure rises > 15cmH2O detected by the intra-abdominal CO2 insufflator.
Change History Complete list of historical versions of study NCT01748643 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2017)
  • Peak Expiratory Flow [ Time Frame: 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)) ]
    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.
  • Forced Expiratory Volume in 1 Second [ Time Frame: 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)) ]
    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.
  • Forced Vital Capacity [ Time Frame: 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)) ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 10, 2012)
  • Respiratory function [ Time Frame: 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)) ]
    Respiratory function will be assessed by measuring peak expiratory flow (PEF) and forced expiratory volume in 1 second (FEV1) 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.
  • Oxygen saturation [ Time Frame: 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)) ]
    Oxygen saturation will be measured non-invasively with a pulse oxymeter
  • Effect of pneumoperitoneum on cerebral tissue oxygenation. [ Time Frame: Participants will be followed for an expected average of 5min after the start of intra-abdominal CO2 insufflation by the surgeon ]
    Using near infrared spectroscopy (Fore-sight®) technology, absolute brain tissue oxygenation can be quantified non-invasively by applying 2 skin electrodes to the forehead of the patient.
  • Effect of neuromuscular blockade on cerebral tissue oxygenation [ Time Frame: Participants will be followed for an expected average of 5min after the intravenous injection of rocuronium ]
    Using near infrared spectroscopy (Fore-sight®) technology, absolute brain tissue oxygenation can be quantified non-invasively by applying 2 skin electrodes to the forehead of the patient.
  • The effect of reversal of neuromuscular blockade (with sugammadex or neostigmine) on cerebral tissue oxygenation [ Time Frame: Participants will be followed for an expected average of 5min after the intravenous injection of sugammadex or neostigmine ]
    Using near infrared spectroscopy (Fore-sight®) technology, absolute brain tissue oxygenation can be quantified non-invasively by applying 2 skin electrodes to the forehead of the patient.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CURES: The Effect of Deep Curarisation and Reversal With Sugammadex on Surgical Conditions and Perioperative Morbidity
Official Title  ICMJE Effect of Deep Curarisation and Reversal With Sugammadex on Surgical Conditions and Perioperative Morbidity in Patients Undergoing Laparoscopic Gastric Bypass Surgery
Brief 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 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.

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:

i. 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Obesity
  • Laparoscopic Gastric Bypass Surgery
  • Surgical Conditions
  • Respiratory Function
  • Cerebral Tissue Oxygenation
Intervention  ICMJE
  • Drug: deep neuromuscular blockade with rocuronium, reversal with sugammadex
    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.
    Other Names:
    • rocuronium: Esmeron
    • sugammadex: Bridion
  • Drug: normal neuromuscular blockade reversal with rocuronium, reversal with neostigmine
    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.
    Other Names:
    • rocuronium: Esmeron
    • neostigmine
    • glycopyrrolate
Study Arms  ICMJE
  • Experimental: Deep neuromuscular blockade, reversal with sugammadex
    a 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.
    Intervention: Drug: deep neuromuscular blockade with rocuronium, reversal with sugammadex
  • Active Comparator: normal neuromuscular blockade, reversal with neostigmine
    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 TOF ratio > 0.9.
    Intervention: Drug: normal neuromuscular blockade reversal with rocuronium, reversal with neostigmine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 10, 2012)
60
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2015
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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

Exclusion Criteria:

  1. Neuromuscular disorders
  2. Allergies to, or contraindication for muscle relaxants, neuromuscular reversing agents, anaesthetics, narcotics
  3. Malignant hyperthermia
  4. Pregnancy or lactation
  5. 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
  6. Chronic obstructive pulmonary disease GOLD classification 2 or higher.
  7. Clinical, radiographic or laboratory findings suggesting upper or lower airway infection
  8. Congestive heart failure.
  9. Pickwick syndrome
  10. Psychiatric illness inhibiting cooperation with study protocol or possibly obscuring results
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01748643
Other Study ID Numbers  ICMJE PVRA-01
2012-005533-37 ( EudraCT Number )
8616-085MISP ( Other Grant/Funding Number: MISP )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pascal Vanelderen, Ziekenhuis Oost-Limburg
Study Sponsor  ICMJE Ziekenhuis Oost-Limburg
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Study Chair: Pieter De Vooght, M.D. Ziekenhuis Oost-Limburg
Study Chair: Jeroen Van Melkebeek, M.D. Ziekenhuis Oost-Limburg
Study Chair: Dimitri Dylst, M.D. Ziekenhuis Oost-Limburg
Study Chair: Maud Beran, M.D. Ziekenhuis Oost-Limburg
Study Chair: Margot Vander Laenen, M.D. Ziekenhuis Oost-Limburg
Study Chair: Jan Van Zundert, M.D., PhD. Ziekenhuis Oost-Limburg
Study Chair: René Heylen, M.D., PhD. Ziekenhuis Oost-Limburg
Study Chair: Hans Verhelst, M.D. Ziekenhuis Oost-Limburg
PRS Account Ziekenhuis Oost-Limburg
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP