Sugammadex vs. Placebo to Prevent Residual Neuromuscular Block in the Post--‐Anesthesia Care Unit

Respiratory Insufficiency Clinical Trial

— Sugammadex  

Official title:

Randomized Double--‐Blinded, Controlled Trial to Compare the Effectiveness of Sugammadex vs. Placebo to Prevent Residual Neuromuscular Block in the Post--‐Anesthesia Care Unit as Evaluated With a Non--‐Invasive Respiratory Volume Monitor

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02822001
• Other study ID #: HSC-MS-16-0241
• Status: Recruiting
• Phase: Phase 4
• Start date: February 16, 2017
• Est. completion date: November 1, 2019

Study information

• Verified date: July 2019
• Source: The University of Texas Health Science Center, Houston
• Contact: George W Williams, MD
• Phone: (713) 500-6680
• Email: George.W.Williams[@]uth.tmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The Primary objective of this study is to determine whether patients who receive sugammadex immediately after tracheal extubation will exhibit a decrease in the incidence of postoperative residual paralysis and an associated decrease in the incidence of postoperative respiratory depression (which can precede critical respiratory events, CRE).

The Secondary objectives are to: a) determine whether patients receiving sugammadex will have a normal TOF ratio (>0.90) indicative of full neuromuscular recovery in the PACU; and b) to improve patient safety by documenting whether postoperative respiratory depression (decreased MV below 80% and 40% of predicted MV as assessed by a Respiratory Volume Monitor) is due to opioid administration vs. postoperative residual neuromuscular block (by comparing postoperative VAS scores and total opioid administered).

Description:

The Investigators plan to enroll 300 patients undergoing surgical procedures requiring general anesthesia with mechanical ventilation will be recruited and consent will be obtained. The subjects will be randomized preoperatively to receive in the OR following the procedure and prior to extubation either sugammadex (Group 1, n=150 patients) or placebo (Group 2, n=150 patients). In all patients, intraoperative surgical and anesthetic management will follow the usual clinical routine at the two enrolling institutions. Once surgery is finished, emergence from anesthesia will occur as per usual clinical routine until the clinician determines that the patient is ready for tracheal extubation. Once the decision to extubate the trachea is made, the patient will receive intravenously either sugammadex 2 mg/kg or placebo in a blinded manner. The patient's trachea will be then extubated, and postoperative anesthetic care will proceed as per usual routine. Patients will then be transferred to the PACU for postoperative care and recovery. (This methodology will ensure that all 300 patients will receive at least the current standard of clinical care. Of the 300 patients, 50% of them (n=150 patients) may benefit from the administration of sugammadex, which may decrease the incidence of residual neuromuscular block.)

1. The ExSpiron will be placed on the patients' chest prior to extubation. ExSpiron data will be collected starting prior to tracheal extubation, during transport from OR to PACU, and in PACU.

2. Patient care staff will be blinded to the ExSpiron numerical and trending data for MV, TV and RR, but the respiratory trace will be displayed to demonstrate that the ExSpiron is functioning. Of note, the gain on the trace is variable so the size of the breath visualized on the screen is not correlated to the volume of the breath. This will maintain blinding of the patient care staff.

3. TOF Monitoring with an objective monitor (TOF--Watch or StimPod) will be used in all patients once the decision to extubate the patients' trachea is made. The monitoring will continue in the PACU until full recovery (TOF=1.0) is documented. Monitoring will be performed as per usual clinical routine via surface ECG electrodes. In the PACU, the current amplitude will be decreased to 30--‐40 mA, current intensities that are used routinely for patient care in other centers and that do not result in patient discomfort.

4. Patient care staff will be blinded to TOF data. Only the investigator assigned to the PACU data retrieval will know the results of TOF Monitoring.

5. Patient care should follow standard hospital protocol.

6. Physiologic monitoring and clinical assessment data will be recorded as per standard protocol in the PACU.

7. All other therapies and medications including oxygen, CPAP, opioids and sedatives will be delivered in accordance with standard of care.

8. Doses and times of all medications (such as opioids, sedatives, etc.) or respiratory interventions (such as albuterol, respiratory treatment, suctioning, high flow oxygen, CPAP, BiPAP, etc.) will be recorded throughout the entire perioperative period (pre--‐op, OR, PACU).

9. Pain scores based on a standard analog scale (1--‐10) will be recorded. These will be obtained per standard clinical practice.

10. Arterial or venous blood gas values and Chest x--‐rays taken in the OR or PACU will be recorded when obtained as part of standard care.

B. Study Procedures

1. Screening and Recruitment:

Study personnel will review the surgery schedule to identify appropriate and eligible patients. Eligible patients will be informed about the study and the study will be explained to them or their parent, guardian or legal representative. They will be able to ask questions. If they would like to participate, written informed consent will be obtained.

2. Randomization:

Patients will be randomized to one of two groups:

administration of sugammadex (n=150) vs. placebo (n=150) prior to tracheal extubation in the OR.

3. Prior to Procedure (in the OR or preoperative area):

I. For RVM monitoring, ExSpiron PadSet will be placed on the patient's thorax (see Appendix A for placement instructions). Deviations from standard placement will be documented. Once in the OR the ExSpiron will be connected and the ExSpiron will be synchronized to the ventilator.

ii. For TOF monitoring, skin ECG electrodes will be placed along the ulnar nerve on the volar forearm, as per routine clinical protocol. Visual or tactile intraoperative monitoring of neuromuscular block level will be performed according to the clinicians' usual routine. At the end of surgery, once the clinician has determined that recovery of neuromuscular block is adequate for maintenance of spontaneous ventilation, the TOF will be determined objectively (it will be measured with the currently available monitor, TOF--‐Watch or StimPod), and then the patient's trachea will be extubated, as per usual clinical routine. In 150 of the 300 patients, a dose of sugammadex (2 mg/kg) will be administered, and then routine TOF measurements will be made in the PACU.

4. Operating Room (OR):

1. Record all medications (dose, route, time)

2. Record surgery start and end times

3. Record position changes

4. Record intubation and extubation times

5. Recovery Room (PACU):

1. Record PACU arrival and check device function.

2. Record all medications (dose, route, time)

3. Record form and dose of administered oxygen & all changes in administered oxygen or respiratory treatments of any kind

4. Record PACU discharge time

5. MV, TV & RR numerical data will be hidden and not available for patient care decisions, but the continuous respiratory trace will be displayed. Patient care providers should not use this trace for clinical decision--‐making. If the trace is absent or grossly abnormal, this should be recorded and study staff notified to ensure proper device function.

6. TOF data will be hidden and not available for patient care decisions

6. Final Discharge Parameters: Record the patients' final discharge date and time (LOS) from the PACU.

7. De--‐identification: All study data will be de--‐identified and identifying information will be linked to a code only accessible to the study staff. The code will be destroyed following final data analysis.

8. Assessment of Subject Safety and Data Safety Monitoring Plan: All patients will be followed by one of the study investigators to ensure there are no complications associated with sugammadex administration (flushing, tachycardia, hypotension, etc). There are no expected complications of RVM monitoring. There are no expected complications associated with TOF monitoring, and in fact, such monitoring has been shown to improve patient safety by decreasing postoperative CREs and other complications.

9. Subject Participation:

1. Recruitment: Subjects will be recruited in the pre--‐ procedure holding areas by the study team members prior to their surgery.

2. Screening Interview: Subject screening will be based on study personnel examining the surgery schedule of the next or same day to identify appropriate procedures scheduled and patient's eligibility.

3. Informed consent process and timing of obtaining of consent: Informed consent will be obtained by the study staff prior to surgery in the preoperative holding area, in patients requiring surgery and general anesthesia and planned extubation in the OR. After a thorough review of the study. Sufficient time will be given to the patients, parents, guardians or legal representative to ask questions and decide on participation.

4. Location where study will be performed: University of Texas, UTHealth at Houston and Mayo Clinic, Jacksonville, Florida operating holding areas, operating and recovery rooms, and intensive care units as applicable.

5. Personnel who will conduct the study include PI and research team members.

10. Subject fees: There are no fees for this study.

11. Procedures to protect subject confidentiality: A unique study ID number will be assigned to each subject as a means to de--‐identify the study data. A code will be kept separately with the PI. Study files will be kept in a locked office in a locked cabinet or a password--‐protected computer with encrypted study files. The location will be the PI office with restricted access. The code will be locked separately from study files in the PI office.

1. Certificate of Confidentiality: N/A

2. How data will be coded, recorded, and stored to protect confidentiality: All data will be de--‐ identified. All data will be linked to the subject study ID by a code.

3. Data will be analyzed by institutional biostatisticians at UTHealth at Houston.

4. Parties who will have access to the data, including the key to the identity code:

only Jaideep Mehta, MD and Sorin J. Brull, MD and primary study staff will have access to the master study log/key. Other investigators and the clinical and engineering staff at Respiratory Motion, Inc. will only have access to de--‐identified data.

5. Parties who will have access to research records: Investigators on the study, Respiratory Motion, Inc. will have access only to de--‐identified records.

6. Collaboration: This study is performed in collaboration with Respiratory Motion, Inc.

7. Alternatives: The alternative to participating in this study is not participating.

8. How new information will be conveyed to the study subject and how it will be documented: Other than the initial explanation of the purpose and plan for the study, the investigators don't expect new information to become available from the study that could affect a subject's willingness to participate. No new information of clinical relevance to the subject is expected from this study. Therefore, no new information will be given to the patient.

9. Payment for a research--‐related injury: This is a minimal risk study. There are no plans to provide other compensation. If a participant is injured during this study, the study doctor will discuss the available medical treatment options with the subject.

12. Outcome: The primary outcome of this study is evaluation of the effects of sugammadex on the incidence of respiration complications postoperatively.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: November 1, 2019
• Est. primary completion date: November 1, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients undergoing surgery with general anesthesia,

• Patients weighing = 80 pounds who are not -intubated prior to surgery,

• Patients who are able to give informed consent.

Exclusion Criteria:

• Patients unable to give informed consent.

• Any patient whose condition will not allow for placement of the electrode PadSet.

• Patients whose tracheas were not extubated in OR or PACU.

• Patients with Impaired Renal Function with a have a known estimated CrCl<30 ml/min

• Patients using oral contraception.

Related Conditions & MeSH terms

• Delayed Emergence from Anesthesia
• Neuromuscular Blockade
• Pulmonary Valve Insufficiency
• Respiratory Insufficiency

Intervention

Drug:
• Sugammadex
Sugammadex is a relatively new compound, a gamma---cyclodextrin molecule that forms an 8---membered ring. When administered to patients who received rocuronium---induced neuromuscular block, sugammadex binds free plasma rocuronium irreversibly, lowering the plasma concentration of free rocuronium. This promotes diffusion of free rocuronium from the neuromuscular junction back into the plasma, where the free rocuronium is again encapsulated. This removal of rocuronium from the neuromuscular junction reverses the neuromuscular block more rapidly and effectively than traditional anticholinesterases (neostigmine).
• Placebo
The patient's trachea will be then extubated, and postoperative anesthetic care will proceed as per usual routine.

Device:
• Train-of-Four Monitoring
This involves delivery of small electrical impulses from a nerve stimulator via surface ECG electrodes to a peripheral nerve (usually the ulnar nerve at the wrist) and measuring the muscle contraction in the innervated muscle (usually the adductor pollicis muscle or the thumb. This testing is used routinely in many centers in awakening patients in the PACU, and it is not associated with any adverse effects or patient discomfort.
• ExSpiron Respiratory Volume Monitoring
The ExSpiron is a non-invasive and safe device cleared by the FDA for monitoring MV, TV and RR. The device requires the application of monitoring PadSets to the patient's skin similar to EKG electrodes and, as such, poses minimal risk.In the proposed trial, we use the ExSpiron to assess the respiratory effects of residual NMB and the effects of sugammadex reversal in decreasing the incidence of pulmonary complications (CREs).

Locations

Country	Name	City	State
United States	Memorial Hermann Hospital	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Health Science Center, Houston	Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of postoperative residual paralysis	Determine whether patients who receive sugammadex immediately after tracheal extubation will exhibit a decrease in the incidence of postoperative residual paralysis.	12 months
Primary	Incidence of postoperative respiratory depression	Associated decrease in the incidence of postoperative respiratory depression (which can precede critical respiratory events, CRE).	12 months
Secondary	Normal TOF ratio (>0.90) indicative of full neuromuscular recovery	Determining whether patients receiving sugammadex will have a normal TOF ratio (>0.90) indicative of full neuromuscular recovery in the PACU	12 months
Secondary	Drug Induced Postoperative Respiratory Depression as measured by Minute Ventilation below 80% and 40% of Predicted Minute Ventilation	Documenting whether postoperative respiratory depression (decreased MV below 80% and 40% of predicted MV as assessed by a Respiratory Volume Monitor) is due to opioid administration vs. postoperative residual neuromuscular block (by comparing postoperative VAS scores and total opioid administered).	12 months