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| ID | Type | Description | Link |
|---|---|---|---|
| 19.4.328 |
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The current trial was designed to investigate the effects of 4.0 mg.kg-1 of sugammadex on efficacy, safety and pharmacokinetics in subjects with severe renal impairment in comparison to subjects with normal renal function.
The results of previous trials showed that the safety profile of sugammadex
observed in subjects with impaired renal function are not appreciably different from subjects with normal renal function. Reoccurrence of neuromuscular blockade was not observed, and sugammadex was safe and generally well tolerated in subjects with severe renal impairment. In a previous trial, subjects (n=15) with severe renal impairment received a dose of 2.0 mg.kg-1 of sugammadex. The effects of the other proposed recommended dose for routine reversal, 4.0 mg.kg-1, on efficacy, safety and pharmacokinetics had not been studied thus far in subjects with severe renal impairment. The objectives of this trial were to assess equivalence with respect to the efficacy of sugammadex in subjects with normal renal function or severe renal impairment, to evaluate the safety of sugammadex in these subject groups and to compare the pharmacokinetic profiles.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Participants with severe renal impairment | Experimental | Participants with severe renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Severe renal impairment was defined as creatinine clearance <30mL/min. |
|
| Participants with normal renal function | Active Comparator | Participants with normal renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Normal renal function was defined as creatinine clearance >=80mL/min. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sugammadex | Drug | Each subject will receive an intravenous (i.v.) single bolus dose of 0.6 mg.kg-1 rocuronium. After this dose, maintenance doses of 0.1 - 0.2 mg.kg-1 rocuronium may be given. In case of maintenance dosing, the target depth of neuromuscular blockade has to be maintained at 1-2 post-tetanic counts (PTC). After the last dose of rocuronium has been administered, the subject will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Recovery of the T4/T1 Ratio to 0.9. | Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery. | start of administration of sugammadex to recovery from neuromuscular blockade |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Recovery of the T4/T1 Ratio to 0.8 | Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery. |
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Inclusion Criteria:
indication for high flux hemodialysis during first 24 hours after
sugammadex administration (for renally impaired group) or CLcr >= 80
mL/min (for control group)
-Scheduled for a surgical procedure under general anesthesia with propofol
requiring neuromuscular relaxation with the use of rocuronium
Exclusion Criteria:
- Subjects known or suspected to have neuromuscular disorders impairing
neuromuscular blockade and/or significant hepatic dysfunction
hyperthermia
-Subjects known or suspected to have an allergy to narcotics, muscle
relaxants or other medication used during general anesthesia
by the sponsor, within 30 days of entering into 19.4.328 (P05769)
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25829395 | Result | Panhuizen IF, Gold SJ, Buerkle C, Snoeck MM, Harper NJ, Kaspers MJ, van den Heuvel MW, Hollmann MW. Efficacy, safety and pharmacokinetics of sugammadex 4 mg kg-1 for reversal of deep neuromuscular blockade in patients with severe renal impairment. Br J Anaesth. 2015 May;114(5):777-84. doi: 10.1093/bja/aet586. Epub 2015 Mar 31. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Participants With Severe Renal Impairment | Participants with severe renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 post-tetanic counts (PTC). Severe renal impairment was defined as creatinine clearance <30mL/min. |
| FG001 | Participants With Normal Renal Function | Participants with normal renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Normal renal function was defined as creatinine clearance >=80mL/min. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Participants With Severe Renal Impairment | Participants with severe renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Severe renal impairment was defined as creatinine clearance <30mL/min. |
| BG001 | Participants With Normal Renal Function |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Time to Recovery of the T4/T1 Ratio to 0.9. | Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery. | Analysis performed using the Intent-to-Treat (ITT) Population, which consisted of all treated subjects who had at least one efficacy measurement. | Posted | Geometric Mean | 95% Confidence Interval | seconds | start of administration of sugammadex to recovery from neuromuscular blockade |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Participants With Severe Renal Impairment | Participants with severe renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Severe renal impairment was defined as creatinine clearance <30mL/min. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA (12.1) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (12.1) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D000077122 | Sugammadex |
| ID | Term |
|---|---|
| D047408 | gamma-Cyclodextrins |
| D003505 | Cyclodextrins |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
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|
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| start of administration of sugammadex to recovery from neuromuscular blockade |
| Time to Recovery of T4/T1 Ratio to 0.7 | Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery. | start of administration of sugammadex to recovery from neuromuscular blockade |
Participants with normal renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Normal renal function was defined as creatinine clearance >=80mL/min. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Participants With Normal Renal Function | Participants with normal renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Normal renal function was defined as creatinine clearance >=80mL/min. |
|
|
|
| Secondary | Time to Recovery of the T4/T1 Ratio to 0.8 | Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery. | Analysis performed using the Intent-to-Treat (ITT) Population, which consisted of all treated subjects who had at least one efficacy measurement. | Posted | Geometric Mean | 95% Confidence Interval | seconds | start of administration of sugammadex to recovery from neuromuscular blockade |
|
|
|
|
| Secondary | Time to Recovery of T4/T1 Ratio to 0.7 | Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery. | Analysis performed using the Intent-to-Treat (ITT) Population, which consisted of all treated subjects who had at least one efficacy measurement. | Posted | Geometric Mean | 95% Confidence Interval | seconds | start of administration of sugammadex to recovery from neuromuscular blockade |
|
|
|
|
| 9 |
| 35 |
| 14 |
| 35 |
| EG001 | Participants With Normal Renal Function | Participants with normal renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Normal renal function was defined as creatinine clearance >=80mL/min. | 3 | 33 | 17 | 33 |
| Subdiaphragmatic abscess | Infections and infestations | MedDRA (12.1) |
|
| Thrombophlebitis septic | Infections and infestations | MedDRA (12.1) |
|
| Anastomotic leak | Injury, poisoning and procedural complications | MedDRA (12.1) |
|
| Incision site haematoma | Injury, poisoning and procedural complications | MedDRA (12.1) |
|
| Narcotic intoxication | Injury, poisoning and procedural complications | MedDRA (12.1) |
|
| Seroma | Injury, poisoning and procedural complications | MedDRA (12.1) |
|
| Wound | Injury, poisoning and procedural complications | MedDRA (12.1) |
|
| Wound haemorrhage | Injury, poisoning and procedural complications | MedDRA (12.1) |
|
| Blood creatinine increased | Investigations | MedDRA (12.1) |
|
| Benign ovarian tumour | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (12.1) |
|
| Ovarian cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (12.1) |
|
| Azotaemia | Renal and urinary disorders | MedDRA (12.1) |
|
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) |
|
| Extremity necrosis | Vascular disorders | MedDRA (12.1) |
|
| Nausea | Gastrointestinal disorders | MedDRA (12.1) |
|
| Vomiting | Gastrointestinal disorders | MedDRA (12.1) |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) |
|
| Procedural hypertension | Injury, poisoning and procedural complications | MedDRA (12.1) |
|
| Procedural hypotension | Injury, poisoning and procedural complications | MedDRA (12.1) |
|
| Procedural nausea | Injury, poisoning and procedural complications | MedDRA (12.1) |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (12.1) |
|
| Neutrophil count increased | Investigations | MedDRA (12.1) |
|
All published results will be based on validated data released by the sponsor and must include one sponsor author. There may be one author from each investigational site, provided that the criteria for authorship are met. In case the proposed publication contains reference to an invention owned by sponsor or to which sponsor otherwise has rights, the sponsor may request a reasonable suspension of the publication in order to be able to file a patent application protecting such invention.
| D003912 |
| Dextrins |
| D013213 | Starch |
| D005936 | Glucans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |